Pharmaceutical compositions of ribociclib

Abstract

Pharmaceutical compositions of ribociclib ora pharmaceutically acceptable salt thereof are disclosed, wherein the compositions are substantially free of nitrosamines. Pharmaceutical products containing said compositions are also disclosed, as well as methods for preparing and storing said pharmaceutical compositions and pharmaceutical products.

Description

[0001] PAT059729-WO-PCT03 1 PHARMACEUTICAL COMPOSITIONS OF RIBOCICLIB TECHNICAL FIELD Pharmaceutical compositions of ribociclib or a pharmaceutically acceptable salt thereof are disclosed, wherein the compositions are substantially free of nitrosamines. Pharmaceutical products containing said compositions are also disclosed, as well as methods for preparing and storing said pharmaceutical compositions and pharmaceutical products. BACKGROUND The term nitrosamine describes a class of compounds having the chemical structure of a nitroso group bonded to an amine (R1N(-R2)-N=O), as shown in the figure below. These compounds can form by a nitrosating reaction between amines (secondary, tertiary, or quaternary amines) and nitrous acid (nitrite salts under acidic conditions) (see “Control of Nitrosamine Impurities in Human Drugs”, Guidance for Industry, U.S. Department of Health and Human Services, Food and Drug Administration, February 2021, Revision 1). Nitrosamine impurities have been discovered in drugs such as angiotensin II receptor blockers, ranitidine, nizatidine, and metformin. However, nitrosamines are considered by the FDA to be probable or possible human carcinogens and as such, the level of nitrosamines in pharmaceutical compositions or products should be kept at a minimum. In particular, the FDA recommends that the risk of nitrosamines should be assessed in any pharmaceutical product. Ribociclib is a potent and highly effective inhibitor of cyclin-dependent kinase 4 and cyclin-dependent kinase 6 (CDK4 / 6) with in vivo activity against hormone receptor-positive, human epidermal growth factor receptor 2- negative (HR+ / HER2-) breast cancer and is currently marketed as KISQALI®. It has the following formula (see e.g. WO 2015 / 022609): Due to the presence of two secondary amines in the ribociclib structure, there is a potential risk of ribociclib forming nitrosamine impurities if exposed to nitrite salts under acidic reaction conditions. Therefore, there PAT059729-WO-PCT03 2 remains a need to provide pharmaceutical compositions and pharmaceutical products of ribociclib or a pharmaceutically acceptable salt thereof which are substantially free of nitrosamines. THE INVENTION The inventors have successfully formulated compositions containing ribociclib or a pharmaceutically acceptable salt thereof which are substantially free of nitrosamines, in particular N-nitroso-ribociclib in free or salt form. The compositions of the invention are intended to be pharmaceutically acceptable (i.e., pharmacologically efficacious and physiologically acceptable). These compositions are suitable for use in medicine, and in particular for the treatment of cancers, such as breast cancer. The breast cancer may be advanced and / or metastatic breast cancer, or it may be early breast cancer. The breast cancer may be hormone receptor-positive (HR+) breast cancer, for example hormone receptor positive human epidermal growth factor receptor 2-negative (HR+ / HER2-) breast cancer. Accordingly, the invention provides a composition comprising or consisting of ribociclib or a pharmaceutically acceptable salt thereof, wherein said composition is substantially free of nitrosamines, in particular N-nitroso- ribociclib in free or salt form. Thus, in one aspect, the composition comprises ribociclib or a pharmaceutically acceptable salt thereof and is substantially free of nitrosamines, or at least substantially free of N-nitroso- ribociclib in free or salt form. In this aspect, the skilled person would appreciate that the composition comprises little or no nitrosamines, in particular little or no N-nitroso-ribociclib in free or salt form. The composition may further comprise one or more pharmaceutically acceptable excipients. In another aspect, the composition consists of ribociclib or a pharmaceutically acceptable salt thereof. In this aspect, the skilled person would appreciate that the composition comprises no nitrosamines, and therefore no N-nitroso-ribociclib in free or salt form. The invention further provides a pharmaceutical product comprising a composition of the invention. In particular, the pharmaceutical product may comprise a plurality of oral dosage forms comprising such a composition, e.g., wherein each of the oral dosage forms is a tablet. A pharmaceutical product of the invention may comprise a composition of the invention and documentation, e.g., in the form of packaging or a package insert. For example, a pharmaceutical product may include a document providing instructions to a patient as to how to administer the composition and / or a document which certifies that the composition is substantially free of nitrosamines, or at least substantially free of N-nitroso-ribociclib in free or salt form. Another aspect of the invention provides methods for preparing ribociclib or a pharmaceutically acceptable salt thereof which is substantially free of nitrosamines, in particular N-nitroso-ribociclib in free or salt form. In particular, the inventors found that limiting the amount of nitrites in the reagents and intermediates that are used to prepare the ribociclib or pharmaceutically acceptable salt thereof provide compositions of ribociclib or PAT059729-WO-PCT03 3 pharmaceutically acceptable salts thereof which are substantially free of nitrosamines. The inventors found that this could be achieved by: Limiting the amount of nitrites in the potassium carbonate that is used in the following deprotection of intermediate B9 to provide ribociclib, B10: ; and / or Limiting the amount of nitrites in the organic or inorganic acid (such as succinic acid) that is to be reacted with ribociclib free base so as to form a pharmaceutically acceptable salt of ribociclib. Another aspect of the invention provides methods for preparing compositions of (i) ribociclib or a pharmaceutically acceptable salt thereof and (ii) one or more pharmaceutically acceptable excipients, wherein said compositions are substantially free of nitrosamines, in particular N-nitroso-ribociclib in free or salt form. The inventors found that limiting the amount of nitrites in any of the excipients and solvents that are used during (i) manufacture of the ribociclib or pharmaceutically acceptable salt thereof or (ii) manufacture of the said compositions, provided compositions which are substantially free of nitrosamines. The inventors found that this could be achieved by: Limiting the amount of nitrites in any of the excipients that are used during the manufacture of the compositions; Limiting the exposure of any solvents that are used during the manufacture of the ribociclib or pharmaceutically acceptable salt thereof to oxygen, e.g., by storing the solvents under an atmosphere in which the percentage of oxygen is less than 21% by volume and / or using the solvents shortly after the solvents are unsealed; Limiting the amount of nitrites in any solvents that are used during the preparation of ribociclib or a pharmaceutically acceptable salt thereof, e.g., by distilling the solvents prior to their use and / or by passing the solvents through an ion exchange resin that is capable of adsorbing nitrites; If forming a pharmaceutically acceptable salt of ribociclib, wherein ribociclib free base is mixed with an acid in the presence of a solvent, then adding the ribociclib free base last to the mixing vessel; PAT059729-WO-PCT03 Filtering any solutions of ribociclib or a pharmaceutically acceptable salt thereof and / or any solutions of the acid that is used to make the salt through a filter which does not comprise a nitrocellulose membrane, e.g., a stainless-steel filter; and / or If preparing a crystalline form of ribociclib or a pharmaceutically acceptable salt thereof, then washing the crystalline form with a solvent which is substantially free of nitrites. Additionally, the inventors found that drying the compositions of ribociclib or a pharmaceutically acceptable salt thereof after mixing the ribociclib or pharmaceutically acceptable salt thereof with one or more excipients provided compositions which were substantially free of nitrosamines despite a period of storage. In particular, when providing the compositions in the form of tablets, the inventors found that drying the tablets during their manufacture (and in particular adding a step of drying the tablets following the compression of the compositions into tablets and the coating of the tablets with a film coating, such as with a moisture barrier film coating) resulted in this reduction in the formation of nitrosamines within the tablets during their subsequent storage. The drying of the tablets until the water activity value of the tablets was less than 0.08, and preferably no more than 0.06, was particularly beneficial. The inventors showed that by conducting this drying step at a relatively low temperature above ambient, and by flowing an atmosphere of low humidity across the tablets at a moderate flow rate, the resulting tablets remained substantially free of nitrosamines despite their long-termstorage under ambient conditions, e.g., at 20 C to 25 C. Temperatures, atmospheres, relative humidities andflow rates for this additional drying step are described elsewhere herein. This use of an additional drying step until a suitable water activity value was reached was found to be a factor in meeting the inventors’ objective ofproducing a pharmaceutical product of ribociclib that avoids the need for cold chain storage at e.g., 2 to 8 C.Lastly, the inventors found that storing the compositions of ribociclib or a pharmaceutically acceptable salt thereof under certain conditions prevents the formation of nitrosamines such as N-nitroso-ribociclib in free or salt form, meaning that the compositions remained substantially free of nitrosamines. This allows for compositions of ribociclib or pharmaceutically acceptable salts thereof which have a shelf life suitable for pharmaceutical use. In particular, the inventors found that the following storage conditions prevent, retard or reduce the formation of nitrosamines: Storing the compositions in the presence of a desiccant; Storing the compositions under an atmosphere in which the percentage of oxygen is less than 21% by volume; PAT059729-WO-PCT03 5 Storing the compositions under an atmosphere in which the humidity is no more than 2.5 g / kg (or a relative humidity of no more than 15%); Providing the compositions in the form of a plurality of oral dosage forms that are packaged within a blister pack such that each oral dosage form is individually packaged within a substantially moisture and / or gas impermeable blister; and / or Storing the compositions under refrigerated conditions, e.g., at about 2 to about 8 C.FIGURES Figure 1 shows the content of nitrite in batches of iPrOH used in the commercial production process. Figure 2 shows a chart of N-nitroso-ribociclib content in the ribociclib drug substance by site. Figure 3 shows the content of nitrite and NOx in both commercial and distilled batches of iPrOH. Figure 4 is a schematic showing the approach taken to ion exchange resin treatment of feed solutions before crystallization of drug substance LEE011 succinate. Figure 5 is a schematic showing the approach taken to nitrite remover screening experiments. Figures 6A-6E show the results of nitrite adsorber (ion exchange resin) screens. In the figures, the columns depict “nitrite_change ratio” and the line graph depicts “DMP433_change ratio”, expressed as percentage values. Figures 7A and 7B are shelf life plots of tablet core experiment 011TC and 012TC under conditions of 40°C / 75% RH and 50°C / 75% RH, respectively. Figures 8A and 8B are shelf life plots of NG4411, NG4412, NG4413 and NH4538 under conditions of 30°C / 75% RH and 40°C / 75% RH, respectively. Figures 9A, 9B, and 9C are shelf life plots of NK1288 and NK6069 under conditions of 2-8°C, 40°C / 75% RH, and 50°C / 75% RH, respectively. Figure 9D is a statistical stability prediction of a standard KISQALI® product across different storage temperatures. Figure 10 shows the XRPD diffractogram of Form E of ribociclib succinate recorded in reflection mode. The figure corresponds to Figure 2 of WO 2020 / 152629. Figure 11 shows the DSC plot of ribociclib succinate Form E at a heating rate of 10 degrees Celsius per minute. This figure corresponds to Figure 7 of WO 2020 / 152629. PAT059729-WO-PCT03 6 Figure 12 shows the thermogravimetric curve of Form E at heating rate at 10 degrees Celsius per minute. This figure corresponds to Figure 11 of WO 2020 / 152629. Figure 13 is a schematic showing the approach taken to solvent distillation and methods of mixing ribociclib with a solution of acid. Figure 14A shows the linearity curve of N-nitroso-ribociclib and Figures 14B-14D show the residual plots for Replicates 1-3, respectively. Figures 15A-15E demonstrate a method of detecting the presence and amount of nitrites using the Griess method. Figure 15A shows the solvent HPLC curve; Figures 15B and 15C show the HPLC curves for Blank Solution 1 and Blank Solution 2, respectively; Figure 15D shows the HPLC curve for the Comparison Solution; and Figure 15E shows the HPLC curve for a Sample solution. Figures 16A-16F show predictive modelling of accelerated stability data for the drug product. Figure 16A shows the Arrhenius plot, Figures 16B-16E show the shelf-life predictions, and Figure 16F shows the APS- based predictions versus real-time stability data. Figures 17A-17C show predictive modelling of accelerated stability data for the drug substance. Figure 17A shows the Arrhenius plot and Figures 17B-17C show the shelf-life predictions. Figure 18 shows predictive modelling stability profiles. Figure 19 shows a validated manufacturing process for ribociclib drug products that are provided in the form of tablets, wherein the process includes blend preparation, roller compaction, compression, and film-coating. As shown in the figure, an additional drying step that uses one of two different drying methods was studied in Example 18 (one method was applied to the film-coated tablets of a first sub-batch A, and one method was applied to the film-coated tablets of a second sub-batch B). Figure 20 shows the water activity of the film-coated tablets of sub-batch A (i.e., film-coated tablets that were dried in the Huettlin HKC-400-device) as a function of drying time. Figure 21 shows the water activity of the film-coated tablets of sub-batch B (i.e., film-coated tablets that were dried using drying vessels in the PIP drying system) as a function of drying time. Figure 22 shows the water activity of the dried ribociclib film-coated tablets of sub-batch A as a function of time, when exposed to environmental conditions with an air humidity of RH NMT 15 %. DEFINITIONS PAT059729-WO-PCT03 7 The terms “substantially free” or “essentially free” in relation to the presence of a given component within e.g., a composition means that no more than 5% by weight of the composition (e.g., no more than 1% by weight of the composition) is that given component. The word “substantially” does not exclude “completely” e.g. a composition which is “substantially free” from Y may be completely free from Y. Where necessary, the word “substantially” may be omitted from the definition of the invention. The term “no more than”, when used to refer to an amount of a particular component in a composition, likewise includes the possibility that the composition is completely free of said component. The use of the articles “a”, “an”, and “the” in both the description and claims are to be construed to cover both the singular and the plural, unless otherwise indicated herein or clearly contradicted by context. The terms “comprising”, “having”, “including”, and “containing” are to be construed as open terms (i.e., meaning “including but not limited to”) unless otherwise noted. Additionally, whenever “comprising” or another open-ended term is used in an embodiment, it is to be understood that the same embodiment can be more narrowly claimed using the intermediate term “consisting essentially of” or the closed term “consisting of”. The term “between” with reference to two values includes those two values e.g., the range “between” 10 mg and 20 mg encompasses e.g., 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 and 20 mg. As used herein the term “about” is understood by the person of skill in the art to reflect the variability in the numerical value it modifies. Values expressed herein are understood to include a range of variability. To reflect this variability, any numerical value used herein incorporates this variability. As such, numerical values used herein encompass that value stated, as well as the value as modified with “about.” In certain embodiments, the term “about” in relation to a numerical value x is optional and means, for example, x±10%, x±5%, or x±1%. Any numerical value used herein may be converted and expressed in any equivalent unit. For example, 1 ppm may be expressed as 1000 ppb. Thus, for example, any reference herein to “a composition comprising no more than 1 ppm” of a given component may be expressed as “a composition comprising no more than 1000 ppb” of said component. “% w / w” means the weight of a component as a percentage of the total weight of a composition, e.g., a dosage form, in which the component is present. For example, a composition comprising “5% w / w of component X” refers to a composition in which the weight of component X is 5% of the total weight of the composition. The term “pharmaceutically acceptable” with respect to a substance refers to the substance as being generally regarded as safe and suitable for use without undue toxicity, irritation, allergic response, and the like, commensurate with a reasonable benefit / risk ratio. PAT059729-WO-PCT03 8 “Pharmaceutically acceptable salt” refers to a salt of a compound that is pharmaceutically acceptable and that possesses (or can be converted to a form that possesses) the desired pharmacological activity of the parent compound. Such salts can be readily made by a person of ordinary skill in the art, and may include acid addition salts, preferably with organic or inorganic acids. Suitable inorganic acids are, for example, halogen acids, such as hydrochloric acid, sulfuric acid, or phosphoric acid. Suitable organic acids are, e.g., succinic acid, carboxylic acids or sulfonic acid, such as fumaric acid or methanesulfonic acid. As used herein, the term “salts” includes co-crystals. The term “co-crystal” refers to a crystalline compound comprising two or more molecular components, e.g., wherein proton transfer between the molecular components is partial or incomplete. Accordingly, the term “pharmaceutically acceptable salt” as used herein encompasses salts and co-crystals as defined herein. The term “solvate” means a molecular complex comprising a compound and one or more pharmaceutically acceptable solvent molecules. Examples of solvent molecules include water and C1-6 alcohols, e.g., ethanol. When the solvate is water, the term “hydrate” may be used. Crystalline forms of ribociclib or a pharmaceutically acceptable salt thereof may be solvates. “Treating” and “treatment” of a disease include the following: (1) inhibiting the disease, i.e., arresting or reducing the development of the disease or its clinical symptoms, and (2) relieving the disease, i.e., causing regression of the disease or its clinical symptoms. Examples of treatment in the context of early breast cancer include a reduced risk of recurrence of the cancer. An example of early breast cancer is stage II and III hormone receptor-positive, human epidermal growth factor receptor 2-negative (HR+ / HER2-) early breast cancer. Examples of treatment in the context of advanced breast cancer include improved progression-free survival (PFS). Tumour growth inhibition, sustained tumour regression and / or delayed tumour regrowth can be observed. An example of advanced breast cancer is hormone receptor-positive, human epidermal growth factor receptor 2-negative (HR+ / HER2-) locally advanced or metastatic breast cancer. The term “effective amount” refers to an amount that may be effective to elicit the desired biological or medical response, including the amount of a compound that, when administered to a subject for treating a disease, is sufficient to effect such treatment for the disease. The effective amount will vary depending on the compound, the disease and its severity, and the age, weight, etc. of the subject to be treated. The effective amount can include a range of amounts. PAT059729-WO-PCT03 9 As used in the context of the present invention, unless otherwise noted, the terms “dose” and “dosage” and “dosage amount” mean the amount of an active compound or pharmaceutical ingredient which is administered to a patient in an individual administration. The term “dosage regimen” (or “dosing regimen”) mean a defined sequence of one or more individual administrations. The one or more “pharmaceutically acceptable excipients” referred to herein can readily be selected by one of ordinary skill in the art and will be determined by the desired mode of administration. Illustrative examples of modes of administration include oral, nasal, parenteral, topical, transdermal, and rectal. Preferably, the mode of administration is oral. The pharmaceutical compositions of this invention may take any pharmaceutical form recognizable to the skilled person as being suitable. Suitable pharmaceutical forms include solid, semisolid, liquid, or lyophilized formulations, such as tablets, powders, capsules, suppositories, suspensions, liposomes, and aerosols. A “desiccant” as used herein refers to a hygroscopic material that absorbs moisture from the air and is used to create and maintain dry spaces i.e. to prevent condensation and maintain low humidity levels. Suitable desiccants can readily be selected by a person of ordinary skill in the art. Examples of desiccants include activated alumina, aerogel, benzophenone, bentonite clay, calcium chloride, calcium oxide, calcium sulphate, cobalt(II) chloride, copper(II) sulphate, lithium chloride, lithium bromide, magnesium chloride hexahydrate, magnesium sulphate, magnesium perchlorate, molecular sieve, phosphorus pentoxide, potassium carbonate, potassium hydroxide, rice, silica gel, sodium, sodium chlorate, sodium chloride, sodium hydroxide, sodium sulphate, sucrose, sulfuric acid, triethylene glycol, and zeolite. For example, the desiccant may be selected from silica gel, molecular sieve, calcium oxide, and calcium sulphate, e.g., silica gel. The phrase “stored in the presence of a desiccant” as used herein refers to the inclusion of a desiccant within the packaging of the compositions and pharmaceutical products described. The phrase will be readily understood by a person of ordinary skill in the art who will be readily able to select suitable packaging. Examples of suitable packaging for the compositions and / or pharmaceutical products described herein include amber glass bottles, rigid high-density polyethylene (HDPE) bottles, Alu-bags, or blister packaging, such as rigid high-density polyethylene (HDPE) bottles, Alu-bags, or blister packaging, e.g., plastic (such as Aclar®) blister packaging, laminate (such as Perlalux®) blister packaging, or alu-alu blister packaging, preferably alu- alu blister packaging. The desiccant may be placed in a separate container from the composition or pharmaceutical product, e.g., in a small HDPE canister or kraft paper bag, prior to inclusion in said packaging. The desiccant may form part of the packaging, e.g., the packaging may comprise a layer, a film, and / or a coating which consists of, comprises, or is derived from a desiccant and which is exposed to the void in which the composition or pharmaceutical product is contained. For example, the packaging for a composition or pharmaceutical product as described herein may be a blister package that includes a blister tray that is an aluminium, laminate or thermoformed plastic sheet with a plurality of blister cells or depressions formed therein. Typically, after the compositions or pharmaceutical products described herein are placed in the cells, the PAT059729-WO-PCT03 10 compositions or products are retained and protected in the respective cells by securing a backing sheet to the blister tray. One or more of the blister cells or depressions (e.g., each of the blister cells or depressions) and / or the backing sheet may be substantially moisture and / or gas impermeable. Thus, in embodiments wherein the composition is provided as a plurality of oral dosage forms, once the blister package is sealed, each oral dosage form may be individually packaged within a substantially moisture and / or gas impermeable blister. Additionally, one or more of the blister cells or depressions (e.g., each of the blister cells or depressions) may comprise a layer, a film and / or a coating which consists of, comprises, or is derived from a desiccant. Alternatively, or additionally, the backing sheet may comprise a layer, a film and / or a coating which consists, comprises, or is derived from a desiccant. Thus, in these embodiments, once the blister package is sealed, the composition is stored in said sealed blister package which also contains a desiccant as a component comprised within the blister package. Values of “humidity” may be given either as absolute humidities (as g / kg) or as relative humidities (as a percentage). A person of ordinary skill in the art will readily understand how to convert between values of relative humidity at a given temperature and values of absolute humidity. For example, a relative humidity of 15% at 22.5 °C may correspond to an absolute humidity of 2.5 g / kg. The term “substantially in accordance with”, with reference to X-ray diffraction peak positions, means that typical peak position and intensity variability are taken into account. For example, one skilled in the art willappreciate that the peak positions (2 ) will show some inter-apparatus variability, typically as much as 0.2°.Further, one skilled in the art will appreciate that relative peak intensities will show inter-apparatus variability as well as variability due to a degree of crystallinity, preferred orientation, prepared sample surface, and other factors known to those skilled in the art, and they should therefore be taken as a qualitative measure only. The phrase “substantially moisture and / or gas impermeable” as used herein may, in accordance with the usual definition in the art, be understood to refer to a material (such as a packaging material, e.g., a blister packaging material) which is substantially impermeable to moisture and / or which is substantially impermeable to gas (such as oxygen) transmission. Preferably, the material will be substantially impermeable to moisture, and optionally the material will also be substantially impermeable to gas (such as oxygen) transmission. The phrase will be readily understood by a person of ordinary skill in the art who will be readily able to select suitable packaging, such as any suitable packaging which is known to protect moisture-sensitive and / or oxygen- sensitive pharmaceutical products. For example, a person of ordinary skill in the art will appreciate that suitable packaging may be packaging which has a low water vapor transmission rate (WVTR), for example packaging which has a WVTR of less than 0.1 g / m2 / day, preferably less than 0.08 g / m2 / day, more preferably less than 0.05 g / m2 / day, and most preferably less than 0.01 g / m2 / day, optionally wherein the WVTR is measured using ASTM F-1249 at 40°C / 75% RH. Additionally, or alternatively, one skilled in the art will appreciate that suitable packaging may be packaging which has a low oxygen transmission rate (OTR), for example packaging which has an OTR of less than 20 cm3 / m2 / day, preferably less than 15 cm3 / m2 / day, more preferably less than 5 PAT059729-WO-PCT03 11 cm3 / m2 / day, and most preferably less than 1 cm3 / m2 / day, optionally wherein the OTR is measured using ASTM D-3985 at 23°C / 50% RH. Suitable blister packaging may include aluminium-aluminium (“alu-alu”) blister packaging, plastic blister packaging (e.g., the PCTFE Aclar® blisters which are commercially available through Honeywell, such as Aclar® UltRx 4000), and laminate blister packaging. Suitable laminate blister packaging may include PVC / PE / PVdC blister packaging (e.g., the triplex Perlalux® blisters which are commercially available through Perlen Packaging, such as Perlalux® Tristar ultra) and laminate blister packaging comprising at least one layer of PCTFE (such as PVC / PCTFE blister packaging, e.g., the Pentapharm® Aclar® PA / 02 blisters which are commercially available through Klöckner Pentaplast). Preferably, the blister packaging is alu-alu blister packaging. Alu-alu packaging is reported to have a WVTR of less than 0.01 g / m2 / day and an OTR of less than 0.5 cm3 / m2 / day. Aclar® UltRx 4000 (PCTFE) blister packaging is reported to have a WVTR of 0.048 g / m2 / day and an OTR of 18 cm3 / m2 / day. Perlalux® Tristar ultra (PVC / PE / PVdC) blister packaging is reported to have a WVTR of 0.06 g / m2 / day and an OTR of 0.067 cm3 / m2 / day. The term “release of the composition” or “release date” or “date of release” as used herein may, in accordance with the usual definition that is used in the art, refer to the date on which a composition comprising or consisting of ribociclib or a pharmaceutically acceptable salt thereof is placed on the market or made available for purchase by third parties. The shelf life may be calculated as starting from this release date, as described in more detail below. The release date should not exceed 30 days from the date of production of the composition. For a composition comprising ribociclib or a pharmaceutically acceptable salt thereof, the date of production of the composition may be taken as the date that the first step is performed involving combining the ribociclib or pharmaceutically acceptable salt thereof with other ingredients. For a composition consisting of ribociclib or a pharmaceutically acceptable salt thereof, the date of production of the composition may be taken as the initial date on which the ribociclib or pharmaceutically acceptable salt thereof is filled into a container for use as a medicinal product. If the composition is released later than 30 days from the date of production, then the date of production, rather than the release date, should be taken as the start of the shelf life. “Ribociclib” refers to the CDK4 / 6 inhibitor known by the IUPAC name 7-cyclopentyl-N,N-dimethyl-2-{[5- (piperazin-1-yl)pyridin-2-yl]amino}-7H-pyrrolo[2,3-d]pyrimidine-6-carboxamide. Ribociclib is currently approved for use in the treatment of breast cancer, in particular hormone receptor-positive, human epidermal growth factor receptor 2-negative (HR+ / HER2-) breast cancer and is marketed as KISQALI®. Ribociclib is also known as “LEE011”. Its CAS registry number is 1211441-98-3, its chemical formula is given below (see WO 2015 / 022609 and WO 2016 / 166703) and its synthesis is specifically described in WO 2010 / 020675:

[0002] PAT059729-WO-PCT03 In accordance with the normal definition that is used in the art, the term “drug substance” as used in the context of the invention described herein refers to ribociclib or a pharmaceutically acceptable salt thereof, e.g., ribociclib succinate, which is referred to in the synthetic schemes included herein as “B12” or “LEE011-B12 (IP)”. Similarly, the term “drug product” as used in the context of the invention that is described herein refers to a pharmaceutical composition comprising ribociclib or a pharmaceutically acceptable salt thereof and one or more pharmaceutically acceptable excipients, e.g., pharmaceutical compositions comprising ribociclib succinate and one or more pharmaceutically acceptable excipients, e.g., film-coated tablets comprising ribociclib and one or more pharmaceutically acceptable excipients. “Nitrosamines” refers to a class of compounds having the chemical structure of a nitroso group bonded to an amine (R1N(-R2)-N=O), as shown in the figure below. These compounds can form by a nitrosating reaction between amines (secondary, tertiary, or quaternary amines) and nitrous acid (nitrite salts under acidic conditions). Examples of nitrosamine impurities that have been found in pharmaceutical products include N-Nitrosodimethylamine (NDMA), N-Nitrosodiethylamine (NDEA), N-Nitrosomethylphenylamine (NMPA), N-Nitrosodiisopropylamine (NDIPA), N-Nitrosoisopropylethylamine (NIPEA), N-Nitrosodibutylamine (NDBA) and N-Nitroso-N-methyl-4- aminobutyric Acid (NMBA). Nitrosamine drug substance-related impurities (NDSRI) are a class of nitrosamine impurities that share structural similarity to the active pharmaceutical ingredient (API) (i.e., the NDSRI has the API or an API fragment in its chemical structure) and are therefore unique to each API. The nitrosamine that is of particular concern in the present invention, which relates to compositions comprising or consisting of ribociclib, is a nitrosamine of ribociclib, the API. Although ribociclib comprises two secondary amines (one acting as a linker between the aromatic rings and the other in the piperazine moiety of the molecule), it has been found that, even under forced conditions, nitrosation does not occur at the aromatic secondary amine. Therefore, in the context of the present invention, “N-nitroso-ribociclib” (also known as “NVP-DMP433” or PAT059729-WO-PCT03 13 “NDSRI DMP433” or “DMP433”) refers to the compound with the chemical name 7-cyclopentyl-N,N-dimethyl- 2-((5-(4-nitrosopiperazin-1-yl)pyridin-2-yl)amino)-7H-pyrrolo[2,3-d]pyrimidine-6-carboxamide i.e. the nitrosamine form of ribociclib given by the following structure: Preferably, the amount of DMP433 in the ribociclib drug substance should not exceed 0.4 ppm, in order to ensure that the end-of-shelf-life limit of 1 ppm for the drug product is met with an appropriate level of confidence (e.g., at least 95%) when the drug product is stored under conditions as specified herein. Similarly, the amount of DMP433 in the ribociclib drug product should preferably not exceed 0.6 ppm or 0.7 ppm at release, in order to ensure that the end-of-shelf-life limit of 1 ppm for the drug product is met with an appropriate level of confidence (e.g., at least 95%) when the drug product is stored under conditions as specified herein. A pharmaceutical composition that is to be used in the treatments that are described herein and which is a tablet comprising an amount of ribociclib or a pharmaceutically acceptable salt thereof that corresponds to 200 mg of ribociclib free base should therefore contain no more than 200 ng of DMP433 in free or salt form. “Palbociclib” refers to the CDK4 / 6 inhibitor known by the IUPAC name 6-Acetyl-8-cyclopentyl-5-methyl-2-{[5- (1-piperazinyl)-2-pyridinyl]amino}pyrido[2,3-d]pyrimidin-7(8H)-one. Palbociclib is currently approved for use in the treatment of breast cancer, in particular hormone-receptor positive, human epidermal growth factor receptor 2-negative (HR+ / HER2-) breast cancer and is marketed as IBRANCE®. Palbociclib is also known as “PD-0332991”. Its CAS registry number is 571190-30-2 and its chemical structure is shown below: The method of testing for the presence and / or total amount of nitrites that is used in the methods of the invention may be any method which allows for the detection and / or quantitation of nitrites in a composition. For example, the method may be the Griess test. The Griess test allows for the detection and analysis of nitrite by the formation of a red-pink colour upon treatment of a nitrite-containing sample with the Griess reagent. The Griess reagent consists of two components in an acidic solution: an aniline derivative and a coupling PAT059729-WO-PCT03 14 agent. The most common arrangements use sulfanilamide and N-(1-naphthyl)ethylenediamine. For example 0.2% N-(1-naphthyl)ethylenediamine dihydrochloride and 2% sulfanilamide in 5% phosphoric acid may be used as a Griess reagent. Other aniline derivatives that may be used in a Griess reagent include sulfanilic acid, nitroaniline, and p-aminoacetophenone. The Griess test involves two subsequent reactions, as shown in the scheme below. When the aniline derivative (e.g., sulfanilamide) is added, the nitrite ion reacts with it in the Griess diazotization reaction to form a diazonium salt, which then reacts with N-(1-naphthyl)ethylenediamine in an azo-coupling reaction, forming a pink-red azo-dye. Using a spectrophotometer, the nitrite concentration can then be quantitatively detected. An example of a method of testing for the presence and / or amount of nitrites is provided herein as Example 16. The method of testing for the presence and / or total amount of nitrosamines (such as the presence and / or total amount of N-nitroso-ribociclib in free or salt form) that is used in the methods of the invention may be any method which allows for the detection of nitrosamines in a composition. For example, the method may involve the Griess test described above. In such a method, the nitrosamines may be first denitrosated (e.g., by photolysis) to form a nitrite, which is then detected in the Griess test. Alternatively, the method may include high performance liquid chromatography (HPLC)- and / or gas chromatography (GC)-mass spectroscopy. An example of a method of testing for the presence and amount of nitrosamines (namely N-nitroso-ribociclib) is provided herein as Example 14. An aspect of the present invention relates to the use of the Griess test and / or high performance liquid chromatography (HPLC) and / or gas chromatography (GC)-mass spectroscopy to detect the presence and / or amount of an impurity in a composition comprising ribociclib or a pharmaceutically acceptable salt thereof, for example wherein the impurity is N-nitroso-ribociclib in free or salt form. For example, high performance liquid chromatography (HPLC)- and gas chromatography (GC)-mass spectroscopy may be used, such as the high performance liquid chromatography (HPLC)- and gas chromatography (GC)-mass spectroscopy method provided herein as Example 14. In one aspect, the present invention provides the use of a gradient elution in a high performance liquid chromatography (HPLC) to detect an impurity in a composition comprising ribociclib or a pharmaceutically PAT059729-WO-PCT03 15 acceptable salt thereof, for example wherein the impurity is N-nitroso-ribociclib in free or salt form. The gradient elution may be used in a high performance liquid chromatography (HPLC)- and gas chromatography (GC)- mass spectroscopy method. The gradient elution may be carried out with a mobile phase A and a mobile phase B as eluents, wherein mobile phase A may comprise, or consist of, formic acid and water, and wherein mobile phase B may comprise, or consist of, methanol. Mobile phase A may comprise, or consist of, 0.1% v / v formic acid in water. The gradient elution may comprise one or more, and preferably each, of the following stages: (1) a stage that is about 2.5 minutes in duration in which the volume of mobile phase A:mobile phase B is about 60:40, (2) a stage that is about 7 minutes in duration in which the volume of mobile phase A:mobile phase B is about 60:40, (3) a stage that is about 0.5 minutes in duration in which the volume of mobile phase A:mobile phase B is about 5:95, (4) a stage that is about 0.5 minutes in duration in which the volume of mobile phase A:mobile phase B is about 5:95, (5) a stage that is about 3.5 minutes in duration in which the volume of mobile phase A:mobile phase B is about 60:40, and (6) a stage in which the volume of mobile phase A:mobile phase B is about 60:40. Preferably, the gradient elution comprises each of the stages indicated as (1)-(6), preferably in the following order: (1), (2), (3), (4), (5) and (6). The gradient elution may be carried out in a reversed-phase C18 chromatographic column (e.g., an Acquity UPLC BEH column, 1.7 μm x 100 x 2.1 mm), at a column temperature of 40 °C, with a flow rate of 0.35 mL / min, and / or with a volume of injection of 10 μL. It will be appreciated that the skilled person would be able to select alternative appropriate columns and / or conditions. It will be appreciated that references herein to an amount (e.g., the total amount, the maximum amount, or specific numerical amounts) of nitrosamines, or to an amount of nitrosamines and salts thereof, such as a reference to a total amount of N-nitroso-ribociclib and salts thereof, refers to the total amount of said nitrosamine in free or salt form. For example, references to a “total amount of N-nitroso-ribociclib in free or salt form of no more than 1 ppm” or to a “total amount of N-nitroso-ribociclib and salts thereof of no more than 1 ppm” are synonymous expressions which mean that both the amount of N-nitroso-ribociclib in the form of its free base and the amount of N-nitroso-ribociclib in the form of any salt thereof together add up to no more than 1 ppm. The same applies to the references herein to a “total amount of ribociclib in free or salt form” or to a “total amount of ribociclib and salts thereof”, which may each be identified as a reference amount against which any such ppm value is to be considered. As such, a reference to the “total amount of N-nitroso-ribociclib in free or salt form of no more than 1 ppm, relative to the total amount of ribociclib in free or salt form” means that the total amount of N-nitroso-ribociclib, when taking account of both any N-nitroso-ribociclib that is present in the form of its free base and any N-nitroso-ribociclib that is present in the form of a salt, is no more than 1 ppm, relative to the total amount of ribociclib when again taking account of both any ribociclib that is present in the form of its free base and any ribociclib that is present in the form of a salt. References to other ppm values of nitrosamines, e.g., other ppm values of N-nitroso-ribociclib or ppm values of other nitrosamines, should be understood in the same way. Similarly, a composition that is “substantially free of N-nitroso-ribociclib and salts thereof” refers to a composition that is substantially free of N-nitroso-ribociclib in free or salt form. PAT059729-WO-PCT03 DETAILED DESCRIPTION OF THE INVENTION The following passages describe features of the aspects and embodiments of the invention in more detail. Unless explicitly stated, and / or unless it would not be technically possible to do so, the following passages are to be read together and the features described therein are combinable. Compositions of the invention An aspect of the present invention relates to a composition comprising or consisting of ribociclib or a pharmaceutically acceptable salt thereof, wherein said composition is substantially free of nitrosamines. The composition may further comprise one or more pharmaceutically acceptable excipients. The nitrosamines may be N-nitroso-ribociclib in free or salt form. Thus, another aspect of the present invention relates to a composition comprising or consisting of ribociclib or a pharmaceutically acceptable salt thereof, wherein said composition is substantially free of N-nitroso-ribociclib in free or salt form. The total amount of nitrosamines (such as N-nitroso-ribociclib in free or salt form) in the composition comprising or consisting of ribociclib or a pharmaceutically acceptable salt thereof may be no more than about 5 ppm, for example no more than about 4 ppm, no more than about 3 ppm, no more than about 2 ppm, or no more than about 1 ppm. As appreciated by one of ordinary skill in the art, particularly in the context of the disclosure herein, such ppm values for the total amount of nitrosamines or the total amount of N-nitroso- ribociclib in free or salt form that is present in a composition are relative to the total amount of the API within the composition, i.e., they are relative to the total amount of ribociclib in free or salt form. Preferably, the total amount of nitrosamines (such as N-nitroso-ribociclib in free or salt form) in the composition comprising or consisting of ribociclib or a pharmaceutically acceptable salt thereof may be no more than about 1 ppm. Thus, another aspect of the invention relates to a composition comprising or consisting of ribociclib or a pharmaceutically acceptable salt thereof, wherein the total amount of nitrosamines (such as N-nitroso- ribociclib in free or salt form) in the composition is no more than about 1 ppm. For example, the total amount of nitrosamines (such as N-nitroso-ribociclib in free or salt form) in the composition may be no more than about 0.9 ppm, no more than about 0.8 ppm, no more than about 0.7 ppm, no more than about 0.65 ppm, no more than about 0.6 ppm, no more than about 0.55 ppm, no more than about 0.5 ppm, no more than about 0.45 ppm, no more than about 0.4 ppm, no more than about 0.35 ppm, no more than about 0.3 ppm, no more than about 0.25 ppm, no more than about 0.2 ppm, no more than about 0.15 ppm, no more than about 0.1 ppm, no more than about 0.05 ppm, or no more than about 0.025 ppm. Preferably, the total amount of nitrosamines (such as N-nitroso-ribociclib in free or salt form) in the composition may be no more than about 0.7 ppm, for example no more than about 0.6 ppm or no more than about 0.4 ppm, relative to the total amount of ribociclib in free or salt form. The total amount of nitrosamines (such as N-nitroso-ribociclib in free or salt form) in the composition comprising or consisting of ribociclib or a pharmaceutically acceptable salt thereof may be no more than the PAT059729-WO-PCT03 17 maximum amount of nitrosamines (such as N-nitroso-ribociclib in free or salt form) that is permitted in such a composition by a regulatory authority. In one aspect of the invention, the total amount of N-nitroso-ribociclib in free or salt form in the composition comprising or consisting of ribociclib or a pharmaceutically acceptable salt thereof may be no more than the maximum amount of N-nitroso-ribociclib that is permitted in such a composition by a regulatory authority. The maximum amount of nitrosamines (such as N-nitroso-ribociclib) that is permitted in such a composition by a regulatory authority may be the amount that is permitted at the time when the composition is prepared, released and / or administered to a patient. Throughout the present disclosure, a reference to a regulatory authority may be considered to be the regulatory authority that is responsible for the country or jurisdiction in which the composition is, or is intended to be, administered. It may be e.g., the FDA, the EMA, the MHRA, Swissmedic, or the PMDA. Thus, another aspect of the invention relates to a composition comprising or consisting of ribociclib or a pharmaceutically acceptable salt thereof, wherein the total amount of nitrosamines (such as N-nitroso-ribociclib in free or salt form) in the composition is no more than the maximum amount of nitrosamines that is permitted in such a composition, by a regulatory authority. Another aspect of the invention relates to a composition comprising or consisting of ribociclib or a pharmaceutically acceptable salt thereof, wherein the total amount of N-nitroso-ribociclib in free or salt form in the composition is no more than the maximum amount of N-nitroso-ribociclib that is permitted in such a composition, by a regulatory authority. The maximum amount of nitrosamines (such as N-nitroso- ribociclib) that is permitted in such a composition by a regulatory authority may be the amount that is permitted at the time when the composition is prepared, released and / or administered to a patient. In one aspect, the regulatory authority is the US FDA, and the maximum amount of nitrosamines that is permitted in the composition comprising or consisting of ribociclib or a pharmaceutically acceptable salt thereof is 0.6 ppm, relative to the total amount of ribociclib in free or salt form. In another aspect, the regulatory authority is the EMA, and the maximum amount of nitrosamines that is permitted in the composition comprising or consisting of ribociclib or a pharmaceutically acceptable salt thereof is 0.7 ppm, relative to the total amount of ribociclib in free or salt form. The total amount of nitrosamines (such as N-nitroso-ribociclib in free or salt form) in the composition comprising or consisting of ribociclib or a pharmaceutically acceptable salt thereof may result in no more than 400 ng / day of said nitrosamines being administered to the patient, when the composition is administered according to an approved dosage regimen of ribociclib or pharmaceutically acceptable salt thereof (for example, in the case that two 200 mg ribociclib tablets are administered per day, no more than 200 ng per tablet of said nitrosamines). Thus, another aspect of the invention relates to a composition comprising or consisting of ribociclib or a pharmaceutically acceptable salt thereof wherein nitrosamines (such as N-nitroso- ribociclib in free or salt form), if present, are present in the composition in an amount that results in no more than 400 ng / day of said nitrosamines being administered to the patient, when the composition is administered according to an approved dosage regimen of ribociclib or pharmaceutically acceptable salt thereof. PAT059729-WO-PCT03 The composition comprising or consisting of ribociclib or a pharmaceutically acceptable salt thereof may be tested, e.g., may be tested to determine the amount of nitrosamines (such as N-nitroso-ribociclib in free or salt form) in the composition. The composition comprising or consisting of ribociclib or a pharmaceutically acceptable salt thereof may be found in such testing to have a total amount of nitrosamines (such as N-nitroso- ribociclib in free or salt form) of no more than about 5 ppm, for example no more than about 4 ppm, no more than about 3 ppm, no more than about 2 ppm, or no more than about 1 ppm. Preferably, the composition comprising or consisting of ribociclib or a pharmaceutically acceptable salt thereof may be found in such testing to have a total amount of nitrosamines (such as N-nitroso-ribociclib in free or salt form) of no more than about 1 ppm. Thus, another aspect of the invention relates to a composition comprising or consisting of ribociclib or a pharmaceutically acceptable salt thereof which has been tested and found to have a total amount of nitrosamines (such as N-nitroso-ribociclib in free or salt form) of no more than about 1 ppm. For example, the composition comprising or consisting of ribociclib or a pharmaceutically acceptable salt thereof may have been tested and found to have a total amount of nitrosamines (such as N-nitroso-ribociclib in free or salt form) of no more than about 0.9 ppm, no more than about 0.8 ppm, no more than about 0.7 ppm, no more than about 0.65 ppm, no more than about 0.6 ppm, no more than about 0.55 ppm, no more than about 0.5 ppm, no more than about 0.45 ppm, no more than about 0.4 ppm, no more than about 0.35 ppm, no more than about 0.3 ppm, no more than about 0.25 ppm, no more than about 0.2 ppm, no more than about 0.15 ppm, no more than about 0.1 ppm, no more than about 0.05 ppm, or no more than about 0.025 ppm. Preferably, the composition comprising or consisting of ribociclib or a pharmaceutically acceptable salt thereof may have been tested and found to have a total amount of nitrosamines (such as N-nitroso-ribociclib in free or salt form) of no more than about 0.7 ppm, for example no more than about 0.6 ppm or no more than about 0.4 ppm, relative to the total amount of ribociclib in free or salt form. The composition comprising or consisting of ribociclib or a pharmaceutically acceptable salt thereof may also be found in such testing to have a total amount of nitrosamines (such as N-nitroso-ribociclib in free or salt form) that is no more than the maximum amount of nitrosamines that is permitted in such a composition, by a regulatory authority. In one aspect, the composition comprising or consisting of ribociclib or a pharmaceutically acceptable salt thereof may be found in such testing to have a total amount of N-nitroso-ribociclib in free or salt form that is no more than the maximum amount of N-nitroso-ribociclib that is permitted in such a composition by a regulatory authority. The maximum amount of nitrosamines (such as N-nitroso-ribociclib) that is permitted in such a composition by a regulatory authority may be the amount that is permitted at the time when the composition is prepared, released and / or administered to a patient. Thus, another aspect of the invention relates to a composition comprising or consisting of ribociclib or a pharmaceutically acceptable salt thereof which has been tested and found to have a total amount of nitrosamines (such as N-nitroso-ribociclib in free or salt form) that is no more than the maximum amount of nitrosamines that is permitted in such a composition by a regulatory authority. Another aspect of the invention relates to a composition comprising or consisting of ribociclib or a pharmaceutically acceptable salt thereof which has been tested and found to have a total amount of N-nitroso-ribociclib in free or salt form that is no more than the maximum amount of N-nitroso- PAT059729-WO-PCT03 19 ribociclib that is permitted in such a composition by a regulatory authority. The maximum amount of nitrosamines (such as N-nitroso-ribociclib) that is permitted in such a composition by a regulatory authority may be the amount that is permitted at the time when the composition is prepared, released and / or administered to a patient. In one aspect, the regulatory authority is the US FDA, and the maximum amount of nitrosamines that is permitted in the composition comprising or consisting of ribociclib or pharmaceutically acceptable salt thereof is 0.6 ppm, relative to the total amount of ribociclib in free or salt form. Therefore, this aspect of the invention relates to a composition comprising or consisting of ribociclib or a pharmaceutically acceptable salt thereof which has been tested and found to have a total amount of nitrosamines (such as N- nitroso-ribociclib in free or salt form) that is no more than about 0.6 ppm, as required by the FDA. In another aspect, the regulatory authority is the EMA, and the maximum amount of nitrosamines that is permitted in the composition comprising or consisting of ribociclib or pharmaceutically acceptable salt thereof is 0.7 ppm, relative to the total amount of ribociclib in free or salt form. Therefore, this aspect of the invention relates to a composition comprising or consisting of ribociclib or a pharmaceutically acceptable salt thereof which has been tested and found to have a total amount of nitrosamines (such as N-nitroso-ribociclib in free or salt form) that is no more than about 0.7 ppm, as required by the EMA. The composition comprising or consisting of ribociclib or a pharmaceutically acceptable salt thereof may contain a total amount of N-nitroso-ribociclib in free or salt form which is no more than about 5 ppm, relative to the total amount of ribociclib in free or salt form, for example no more than about 4 ppm, no more than about 3 ppm, no more than about 2 ppm, or no more than about 1 ppm, relative to the total amount of ribociclib in free or salt form. Preferably, the composition comprising or consisting of ribociclib or a pharmaceutically acceptable salt thereof may contain a total amount of N-nitroso-ribociclib in free or salt form which is no more than about 1 ppm, relative to the total amount of ribociclib in free or salt form. Thus, another aspect of the invention relates to a composition comprising or consisting of ribociclib or a pharmaceutically acceptable salt thereof, wherein the total amount of N-nitroso-ribociclib in free or salt form is no more than about 1 ppm, relative to the total amount of ribociclib in free or salt form. In some embodiments, the total amount of N- nitroso-ribociclib in free or salt form may be no more than about 0.9 ppm, no more than about 0.8 ppm, no more than about 0.7 ppm, no more than about 0.65 ppm, no more than about 0.6 ppm, no more than about 0.55 ppm, no more than about 0.5 ppm, no more than about 0.45 ppm, no more than about 0.4 ppm, no more than about 0.35 ppm, no more than about 0.3 ppm, no more than about 0.25 ppm, no more than about 0.2 ppm, no more than about 0.15 ppm, no more than about 0.1 ppm, no more than about 0.05 ppm, or no more than about 0.025 ppm, relative to the total amount of ribociclib in free or salt form. Preferably, the invention relates to a composition comprising or consisting of ribociclib or a pharmaceutically acceptable salt thereof, wherein the total amount of N-nitroso-ribociclib in free or salt form is no more than about 0.7 ppm, for example no more than about 0.6 ppm, or no more than about 0.4 ppm, relative to the total amount of ribociclib in free or salt form. PAT059729-WO-PCT03 20 The total amount of N-nitroso-ribociclib in free or salt form in the composition comprising or consisting of ribociclib or a pharmaceutically acceptable salt thereof may result in no more than 400 ng / day of said N-nitroso- ribociclib in free or salt form being administered to the patient, when the composition is administered according to an approved dosage regimen of ribociclib or pharmaceutically acceptable salt thereof (for example, in the case that two 200 mg ribociclib tablets are administered per day, no more than 200 ng per tablet of said nitrosamines). Thus, another aspect of the invention relates to a composition comprising or consisting of ribociclib or a pharmaceutically acceptable salt thereof, wherein N-nitroso-ribociclib in free or salt form, if present, is present in the composition in an amount that results in no more than 400 ng / day of said N-nitroso- ribociclib in free or salt form being administered to the patient, when the composition is administered according to an approved dosage regimen of ribociclib or pharmaceutically acceptable salt thereof (for example, in the case that two 200 mg ribociclib tablets are administered per day, no more than 200 ng per tablet of said nitrosamines). The composition comprising or consisting of ribociclib or a pharmaceutically acceptable salt thereof may contain an amount of total nitrosamines, including both N-nitroso-ribociclib in free or salt form and other nitrosamines, which is no more than about 5 ppm, for example no more than about 4 ppm, no more than about 3 ppm, no more than about 2 ppm, or no more than about 1 ppm. Preferably, the composition comprising or consisting of ribociclib or a pharmaceutically acceptable salt thereof may contain an amount of total nitrosamines, including both N-nitroso-ribociclib in free or salt form and other nitrosamines, which is no more than about 1 ppm. Thus, another aspect of the invention relates to a composition comprising or consisting of ribociclib or a pharmaceutically acceptable salt thereof, wherein the amount of total nitrosamines, including N- nitroso-ribociclib in free or salt form and other nitrosamines, is no more than about 1 ppm. In some embodiments, the amount of total nitrosamines, including both N-nitroso-ribociclib in free or salt form and other nitrosamines, may be no more than about 0.9 ppm, no more than about 0.8 ppm, no more than about 0.7 ppm, no more than about 0.65 ppm, no more than about 0.6 ppm, no more than about 0.55 ppm, no more than about 0.5 ppm, no more than about 0.45 ppm, no more than about 0.4 ppm, no more than about 0.35 ppm, no more than about 0.3 ppm, or no more than about 0.25 ppm. Preferably, the invention relates to a composition comprising or consisting of ribociclib or a pharmaceutically acceptable salt thereof, wherein the amount of total nitrosamines, including N-nitroso-ribociclib in free or salt form and other nitrosamines, is no more than about 0.7 ppm, for example no more than about 0.6 ppm or no more than about 0.4 ppm, relative to the total amount of ribociclib in free or salt form. The amount of total nitrosamines, including both N-nitroso-ribociclib in free or salt form and other nitrosamines, in the composition comprising or consisting of ribociclib or a pharmaceutically acceptable salt thereof may result in no more than 400 ng / day of said total nitrosamines being administered to the patient, when the composition is administered according to an approved dosage regimen of ribociclib or pharmaceutically acceptable salt thereof (for example, in the case that two 200 mg ribociclib tablets are administered per day, no more than 200 ng per tablet of said nitrosamines). Thus, another aspect of the invention relates to a PAT059729-WO-PCT03 21 composition comprising or consisting of ribociclib or a pharmaceutically acceptable salt thereof, wherein the amount of total nitrosamines, including both N-nitroso-ribociclib in free or salt form and other nitrosamines, present in the composition results in no more than 400 ng / day of said total nitrosamines being administered to the patient, when the composition is administered according to an approved dosage regimen of ribociclib or pharmaceutically acceptable salt thereof (for example, in the case that two 200 mg ribociclib tablets are administered per day, no more than 200 ng per tablet of said nitrosamines). The composition comprising or consisting of ribociclib or a pharmaceutically acceptable salt thereof may contain a total amount of NDMA, NDEA, NMPA, NDIPA, NIPEA, NDBA and / or NMBA, which is, in each case, no more than about 100 ppb. For example, the composition comprising or consisting of ribociclib or a pharmaceutically acceptable salt thereof may contain a total amount of N-nitrosodimethylamine (NDMA) which is no more than about 100 ppb. The composition may be substantially free, such as completely free, of NDMA. The composition may be substantially free, such as completely free, of NDMA, NDEA, NMPA, NDIPA, NIPEA, NDBA and NMBA. As would be understood by one of ordinary skill in the art, when a maximum amount of a component is being specified, such as e.g., an amount or total amount of “no more than” a specified value x, then the reader is being urged not to exceed the specified value in order to increase the benefit that is obtained. One of ordinary skill in the art would therefore understand that in such embodiments, the variability that would otherwise be optionally associated with the given numerical value x, whether it is preceded by the term “about” or not, is preferably absent, i.e., any amount that is greater than x is not permitted. In such cases in which the option of variability is not exercised, the value x might alternatively be expressed as x±0%. Similar considerations apply mutatis mutandis for any reference to an amount which is “less than” a specified value x. Ribociclib Ribociclib (also known as “LEE011” and referred to in the synthetic schemes included herein as “B10” or “LEE011-B10 (IP-1)”) is a potent and highly effective CDK4 / 6 inhibitor with in vivo activity against hormone receptor-positive, human epidermal growth factor receptor 2-negative (HR+ / HER2-) breast cancer. Ribociclib or its pharmaceutically acceptable salts can be present within the composition in solvated or unsolvated form, and references to “ribociclib or a pharmaceutically acceptable salt thereof” include both of these forms. In particular, references to ribociclib or a pharmaceutically acceptable salt thereof include ribociclib, a pharmaceutically acceptable salt of ribociclib, a pharmaceutically acceptable hydrate or solvate of ribociclib, and a pharmaceutically acceptable hydrate or solvate of a pharmaceutically acceptable salt of ribociclib. Typically, ribociclib is included as its succinate salt (ribociclib succinate, referred to in the synthetic schemes included herein as “B12” or “LEE011-B12 (IP)”), having the formula below: PAT059729-WO-PCT03 As used herein, and in the absence of a specific reference to a particular pharmaceutically acceptable salt and / or solvate of the compound of ribociclib (e.g., ribociclib succinate), any dosages, whether expressed in e.g., milligrams or as a % by weight, should be taken as referring to the amount of ribociclib free base, i.e., the amount of: For example, therefore, a reference to “400 mg of ribociclib or a pharmaceutically acceptable salt thereof” means an amount of ribociclib or a pharmaceutically acceptable salt thereof which provides the same amount of ribociclib as 400 mg of ribociclib free base, i.e., 508.7 mg of ribociclib succinate. Similarly, a reference to a “200 mg ribociclib tablet” means a tablet which includes an amount of ribociclib or a pharmaceutically acceptable salt thereof which provides the same amount of ribociclib as 200 mg of ribociclib free base, i.e., 254.4 mg of ribociclib succinate. The total amount of ribociclib or a pharmaceutically acceptable salt thereof included in the compositions of the invention may provide the same amount of ribociclib as about 50-1000 mg of ribociclib free base, e.g., about 100-1000 mg of ribociclib free base. The total amount of ribociclib or a pharmaceutically acceptable salt thereof included in the compositions of the invention may provide the same amount of ribociclib as about 50 mg, 100 mg, 200 mg, 400 mg, or 600 mg of ribociclib free base. The total amount of ribociclib or a pharmaceutically acceptable salt thereof included in the compositions of the invention may provide the same amount of ribociclib as about 200 mg of ribociclib free base. The total amount of ribociclib or a pharmaceutically acceptable salt thereof included in the compositions of the invention may provide the same amount of ribociclib as about 400 mg of ribociclib free base. The total amount of ribociclib or a pharmaceutically acceptable salt thereof included in the compositions of the invention may provide the same amount of ribociclib as about 600 mg ribociclib free base. Preferably, the total amount of ribociclib or a pharmaceutically acceptable salt thereof in the compositions of the invention provides the same amount of ribociclib as about 200 mg of ribociclib free base. PAT059729-WO-PCT03 23 The ribociclib or pharmaceutically acceptable salt thereof included in the compositions of the invention may be in the solid form. The ribociclib or pharmaceutically acceptable salt thereof included in the compositions of the invention may be of any solid form. For example, the ribociclib or pharmaceutically acceptable salt thereof may be in amorphous or crystalline form. Examples of suitable crystalline forms of ribociclib and pharmaceutically acceptable salts thereof are provided in WO 2020 / 152629 and in U.S. Patent No. 9,868,739, which are incorporated by reference in their entirety. For example, the ribociclib or pharmaceutically acceptable salt thereof may be a crystalline form of ribociclib succinate. The crystalline form of ribociclib succinate may be Form E as described in WO 2020 / 152629, which is incorporated by reference in its entirety. In particular, Examples 2, 6, 12, 16, and 19 of WO 2020 / 152629 describe the formation and characterization of Form E of ribociclib succinate, and these examples are incorporated by reference. Thus, the ribociclib or pharmaceutically acceptable salt thereof included in the compositions of the invention may be characterized by an X-ray powder diffraction pattern having characteristic peaks expressed in degrees 2-Theta at angles of 11.0° + / - 0.2°, 13.0 + / - 0.2°, and 17.2° + / - 0.2°. The ribociclib or pharmaceutically acceptable salt thereof included in the compositions of the invention may be characterized by an X-ray powder diffraction patten having at least four characteristic peaks expressed in degrees 2-Theta selected from 11.0° + / - 0.2°, 13.0 + / - 0.2°, 17.2° + / - 0.2°, 20.0 + / - 0.2°, and 23.0 + / - 0.2°. The ribociclib or pharmaceutically acceptable salt thereof included in the compositions of the invention may be characterized by an X-ray powder diffraction patten having at least five characteristic peaks expressed in degrees 2-Theta selected from 8.8° + / - 0.2°, 11.0° + / - 0.2°, 13.0 + / - 0.2°, 13.7 + / - 0.2°, 15.7 + / - 0.2°, 17.2 + / - 0.2°, 18.7 + / - 0.2°, 20.0 + / - 0.2°, 21.1 + / - 0.2°, 23.0 + / - 0.2°, and 24.9° + / - 0.2°. The ribociclib or pharmaceutically acceptable salt thereof included in the compositions of the invention may be characterized by an X-ray powder diffraction patten having at least seven characteristic peaks expressed in degrees 2-Theta selected from 7.9° + / - 0.2°, 8.8° + / - 0.2°, 11.0° + / - 0.2°, 12.4° + / - 0.2°, 13.0 + / - 0.2°, 13.7 + / - 0.2°, 15.7 + / - 0.2°, 17.2 + / - 0.2°, 18.7 + / - 0.2°, 20.0 + / - 0.2°, 21.1 + / - 0.2°, 23.0 + / - 0.2°, and 24.9° + / - 0.2°. The ribociclib or pharmaceutically acceptable salt thereof included in the compositions of the invention may exhibit an X-ray powder diffraction pattern substantially in accordance with Figure 10 (corresponding to Figure 2 of WO 2020 / 152629) or the following table (corresponding to Table 4 of WO 2020 / 152629). XRPD peak table for Form E of ribociclib succinate Angle (°2 ) Intensity (qualitative)7.9 Low 8.8 Medium 11.0 Medium 12.4 Low PAT059729-WO-PCT03 24 13.0 High 13.7 Medium 15.7 Medium 17.4 Low 18.7 Medium 20.0 High 21.1 Medium 23.0 High 24.9 Medium (High intensity >50%; 50%>Medium>20%; Low <20%)The value of each of the 2 values is accurate within ±0.2.Dosage forms of the invention The compositions of the invention may be administered by any mode recognizable by the skilled person as being suitable. Illustrative examples of modes of administration include oral, nasal, parenteral, topical, transdermal, and rectal. Preferably, the compositions of the invention are orally administrable. The pharmaceutical compositions of this invention may take any pharmaceutical form recognizable to the skilled person as being suitable. Suitable pharmaceutical forms include solid, semisolid, liquid, or lyophilized formulations, such as tablets, powders, capsules, suppositories, suspensions, liposomes, and aerosols. Preferably, the compositions of the invention may be administered in the form of a solid oral dosage form, for example a tablet, capsule, pill, or a patch. The composition of the invention may be administered in the form of a capsule, e.g. a biodegradable capsule. Alternatively, the composition of the invention may be administered in a solid oral dosage form which is not a capsule. Preferably, the composition of the invention may be administered in the form of a tablet. Alternatively, the compositions of the invention may be in the form of a liquid dosage form, for example a solution or a suspension. The compositions of the invention may be present in a sealed container. The compositions of the invention may further be under an atmosphere in which the humidity is no more than 2.5 g / kg (or the relative humidity is no more than 15%) and / or the percentage of oxygen is less than 21% by volume. The atmosphere may be air, or it may be an inert gas such as helium, nitrogen, argon, or neon. Preferably, the inert atmosphere is nitrogen. PAT059729-WO-PCT03 In one embodiment, the composition may be provided as a plurality of oral dosage forms (e.g., the composition may be divided into a plurality of oral dosage forms) that are packaged within a blister pack such that each oral dosage form is individually packaged. Preferably the blister pack is substantially moisture and / or gas impermeable, more preferably such that each oral dosage form is individually packaged within a substantially moisture and / or gas impermeable blister. Materials for packaging that are substantially moisture and / or gas impermeable, e.g., materials that may be used to provide blister packs, are described elsewhere herein. Preferably, the substantially moisture and / or gas impermeable blister is an alu-alu blister. The composition may be present in a sealed container which also contains a desiccant, or the composition may be present in a sealed pharmaceutical package which also contains a desiccant in a separate container. The composition may be stored in the presence of a desiccant. The desiccant may be selected from the following list: activated alumina, aerogel, benzophenone, bentonite clay, calcium chloride, calcium oxide, calcium sulphate, cobalt(II) chloride, copper(II) sulphate, lithium chloride, lithium bromide, magnesium chloride hexahydrate, magnesium sulphate, magnesium perchlorate, molecular sieve, phosphorus pentoxide, potassium carbonate, potassium hydroxide, rice, silica gel, sodium, sodium chlorate, sodium chloride, sodium hydroxide, sodium sulphate, sucrose, sulfuric acid, triethylene glycol, and zeolite. Preferably, the desiccant may be selected from silica gel, molecular sieve, calcium oxide, and calcium sulphate. More preferably, the desiccant may be silica gel. The compositions of the invention may be administered in the form of a solid oral dosage form, such as a tablet. For example, a pharmaceutical product may be provided which comprises a plurality of oral dosage forms, e.g., a plurality of tablets. The pharmaceutical product may comprise at least 5, at least 10, at least 15, at least 20, at least 25, at least 30, at least 35, at least 40, at least 45, at least 50 or at least 60 of said oral dosage forms, such as 7, 14, 21, 28, 35, 42, 49, 56, 63 or 70 of said oral dosage forms. Each of the oral dosage forms in the pharmaceutical product may satisfy a requirement as specified herein for the total amount of nitrosamines and / or the total amount of N-nitroso-ribociclib in free or salt form that is present in a composition comprising ribociclib or a pharmaceutically acceptable salt thereof. Each of the oral dosage forms may satisfy the same requirement. Each of the oral dosage forms, e.g., each of the tablets, may comprise or consist of ribociclib or a pharmaceutically acceptable salt thereof, wherein: (i) each of the oral dosage forms is substantially free of N-nitroso-ribociclib in free or salt form, (ii) the total amount of N-nitroso-ribociclib in free or salt form in each of the oral dosage forms is no more than 1 ppm, relative to the total amount of ribociclib in free or salt form, preferably wherein the total amount of N- nitroso-ribociclib in free or salt form in each of the oral dosage forms is no more than 0.7 ppm, more preferably no more than 0.6 ppm, relative to the total amount of ribociclib in free or salt form, or PAT059729-WO-PCT03 26 (iii) the total amount of N-nitroso-ribociclib in free or salt form in each of the oral dosage forms is no more than the maximum amount of nitrosamines that is permitted in such a composition, by a regulatory authority, for example wherein the total amount of N-nitroso-ribociclib in free or salt form in each of the oral dosage forms is no more than the maximum amount of N-nitroso-ribociclib that is permitted in such a composition, by a regulatory authority. As would be understood by one of ordinary skill in the art in the absence of any explicit statement to the contrary, each of the oral dosage forms within a pharmaceutical product will have the same composition, save for the fact that there may be some degree of variation between these oral dosage forms in terms of the total amount of nitrosamines and / or the total amount of N-nitroso-ribociclib in free or salt form. For example, each of these oral dosage forms may satisfy the same requirement for the total amount of nitrosamines and / or the total amount of N-nitroso-ribociclib (e.g., the total amount of N-nitroso-ribociclib in free or salt form in each of the oral dosage forms may be no more than 1 ppm, preferably no more than 0.7 ppm, and more preferably no more than 0.6 ppm, relative to the total amount of ribociclib in free or salt form in each of the oral dosage forms), but the exact total amount(s) in each of these oral dosage forms may vary between them (e.g., one or more of the oral dosage forms may be completely free of N-nitroso-ribociclib in free or salt form, and / or one or more of the oral dosage forms may comprise about 0.1 ppm of N-nitroso-ribociclib in free or salt form, and / or one or more of the oral dosage forms may comprise about 0.2 ppm of N-nitroso-ribociclib in free or salt form, etc.). As a person of ordinary skill in the art will readily appreciate, such variations may occur as a result of e.g., the different individual oral dosage forms within a particular pharmaceutical product being manufactured using different batches of ribociclib or of a pharmaceutical acceptable salt thereof and / or using different batches or sources of excipients. Pharmaceutical Products of the Invention Another aspect of the invention relates to a pharmaceutical product comprising a composition of the invention and a document providing instructions to a patient as to how to administer the composition. The document may provide the instructions either directly or via a link to an electronic database. The pharmaceutical product of the invention may comprise a document which certifies, either directly or via a link to an electronic database, that the total amount of nitrosamines (such as N-nitroso-ribociclib in free or salt form) in the composition is no more than about 5 ppm, for example no more than about 4 ppm, no more than about 3 ppm, no more than about 2 ppm, or no more than about 1 ppm. Preferably, the document may certify, either directly or via a link to an electronic database, that the total amount of nitrosamines (such as N-nitroso- ribociclib in free or salt form) in the composition is no more than about 1 ppm. Thus, another aspect of the invention relates to a pharmaceutical product containing: (a) a pharmaceutical composition comprising ribociclib or a pharmaceutically acceptable salt thereof; and (b) a document which certifies, either directly or via a link to an electronic database, that the total amount of nitrosamines (such as N-nitroso-ribociclib in free or salt form) in the composition is no more than about 1 ppm. For example, the document may certify, either PAT059729-WO-PCT03 27 directly or via a link to an electronic database, that the total amount of nitrosamines (such as N-nitroso-ribociclib in free or salt form) may be no more than about 0.9 ppm, no more than about 0.8 ppm, no more than about 0.7 ppm, no more than about 0.65 ppm, no more than about 0.6 ppm, no more than about 0.55 ppm, no more than about 0.5 ppm, no more than about 0.45 ppm, no more than about 0.4 ppm, no more than about 0.35 ppm, no more than about 0.3 ppm, no more than about 0.25 ppm. Preferably, an aspect of the invention relates to a pharmaceutical product containing: (a) a pharmaceutical composition comprising ribociclib or a pharmaceutically acceptable salt thereof; and (b) a document which certifies, either directly or via a link to an electronic database, that the total amount of nitrosamines (such as N-nitroso-ribociclib in free or salt form) in the composition is no more than about 0.7 ppm, for example no more than about 0.6 ppm. The pharmaceutical product of the invention may comprise a document which certifies, either directly or via a link to an electronic database, that the total amount of nitrosamines (such as N-nitroso-ribociclib in free or salt form) in the composition results in no more than 400 ng / day of said nitrosamines being administered to the patient, when the composition is administered according to an approved dosage regimen of ribociclib or pharmaceutically acceptable salt thereof. Thus, another aspect of the invention relates to a pharmaceutical product containing: (a) a pharmaceutical composition comprising ribociclib or a pharmaceutically acceptable salt thereof; and (b) a document which certifies, either directly or via a link to an electronic database, that the total amount of nitrosamines (such as N-nitroso-ribociclib in free or salt form) in the composition results in no more than 400 ng / day of said nitrosamines being administered to the patient, when the composition is administered according to an approved dosage regimen of ribociclib or pharmaceutically acceptable salt thereof. The pharmaceutical product of the invention may also comprise a document which certifies, either directly or via a link to an electronic database, that the total amount of nitrosamines in the composition is no more than the maximum amount of nitrosamines that is permitted in such a composition by a regulatory authority. Thus, another aspect of the invention relates to a pharmaceutical product containing: (a) a pharmaceutical composition comprising ribociclib or a pharmaceutically acceptable salt thereof; and (b) a document which certifies, either directly or via a link to an electronic database, that the total amount of nitrosamines in the composition is no more than the maximum amount of nitrosamines that is permitted in such a composition by a regulatory authority. In one of the above aspects, the document may certify, either directly or via a link to an electronic database, that the total amount of N-nitroso-ribociclib in free or salt form in the composition is no more than the maximum amount of N-nitroso-ribociclib that is permitted in such a composition by a regulatory authority. The maximum amount of nitrosamines (such as N-nitroso-ribociclib) that is permitted in such a composition by a regulatory authority may be the amount that is permitted at the time when the composition is prepared, released and / or administered to a patient. In one aspect, the regulatory authority is the US FDA, and the maximum amount of nitrosamines that is permitted in the composition comprising or consisting of ribociclib or pharmaceutically acceptable salt thereof is 0.6 ppm. Thus, such an aspect of the invention relates to a pharmaceutical product containing: (a) a pharmaceutical composition comprising ribociclib or a PAT059729-WO-PCT03 28 pharmaceutically acceptable salt thereof; and (b) a document which certifies, either directly or via a link to an electronic database, that the total amount of nitrosamines in the composition is no more than about 0.6 ppm, relative to the total amount of ribociclib in free or salt form. In another aspect, the regulatory authority is the EMA, and the maximum amount of nitrosamines that is permitted in the composition comprising or consisting of ribociclib or pharmaceutically acceptable salt thereof is 0.7 ppm. Thus, such an aspect of the invention relates to a pharmaceutical product containing: (a) a pharmaceutical composition comprising ribociclib or a pharmaceutically acceptable salt thereof; and (b) a document which certifies, either directly or via a link to an electronic database, that the total amount of nitrosamines in the composition is no more than about 0.7 ppm, relative to the total amount of ribociclib in free or salt form. The pharmaceutical product of the invention may also comprise a document which certifies, either directly or via a link to an electronic database, that the total amount of N-nitroso-ribociclib in free or salt form is no more than about 5 ppm, relative to the total amount of ribociclib in free or salt form, for example no more than about 4 ppm, no more than about 3 ppm, no more than about 2 ppm, or no more than about 1 ppm, relative to the total amount of ribociclib in free or salt form. Preferably, the document may certify, either directly or via a link to an electronic database, that the total amount of N-nitroso-ribociclib in free or salt form is no more than about 1 ppm, relative to the total amount of ribociclib in free or salt form. Thus, another aspect of the invention relates to a pharmaceutical product containing: (a) a pharmaceutical composition comprising ribociclib or a pharmaceutically acceptable salt thereof; and (b) a document which certifies, either directly or via a link to an electronic database, that the total amount of N-nitroso-ribociclib in free or salt form is no more than about 1 ppm, relative to the total amount of ribociclib in free or salt form. The document may certify, either directly or via a link to an electronic database, that the total amount of N-nitroso-ribociclib in free or salt form is no more than about 0.9 ppm, no more than about 0.8 ppm, no more than about 0.7 ppm, no more than about 0.6 ppm, no more than about 0.5 ppm, no more than about 0.4 ppm, no more than about 0.3 ppm, no more than about 0.2 ppm, no more than about 0.1 ppm, no more than about 0.05 ppm, or no more than about 0.025 ppm, relative to the total amount of ribociclib in free or salt form. Preferably, an aspect of the invention relates to a pharmaceutical product containing: (a) a pharmaceutical composition comprising ribociclib or a pharmaceutically acceptable salt thereof; and (b) a document which certifies, either directly or via a link to an electronic database, that the total amount of N-nitroso-ribociclib in free or salt form is no more than about 0.7 ppm, for example no more than about 0.6 ppm, relative to the total amount of ribociclib in free or salt form. The pharmaceutical product of the invention may comprise a document which certifies, either directly or via a link to an electronic database, that the total amount of N-nitroso-ribociclib in free or salt form in the composition results in no more than 400 ng / day of said N-nitroso-ribociclib in free or salt form being administered to the patient, when the composition is administered according to an approved dosage regimen of ribociclib or pharmaceutically acceptable salt thereof. Thus, another aspect of the invention relates to a pharmaceutical product containing: (a) a pharmaceutical composition comprising ribociclib or a pharmaceutically acceptable salt thereof; and (b) a document which certifies, either directly or via a link to an electronic database, that the PAT059729-WO-PCT03 29 total amount of N-nitroso-ribociclib in free or salt form is present in the composition results in no more than 400 ng / day of said N-nitroso-ribociclib in free or salt form being administered to the patient, when the composition is administered according to an approved dosage regimen of ribociclib or pharmaceutically acceptable salt thereof. The pharmaceutical product of the invention may also comprise a document which certifies, either directly or via a link to an electronic database, that the amount of total nitrosamines, including both N-nitroso-ribociclib in free or salt form and other nitrosamines, is no more than about 5 ppm, for example no more than about 4 ppm, no more than about 3 ppm, no more than about 2 ppm, or no more than about 1 ppm. Preferably, the document may certify, either directly or via a link to an electronic database, that the amount of total nitrosamines, including both N-nitroso-ribociclib in free or salt form and other nitrosamines, is no more than about 1 ppm. Thus, another aspect of the invention relates to a pharmaceutical product containing: (a) a pharmaceutical composition comprising ribociclib or a pharmaceutically acceptable salt thereof; and (b) a document which certifies, either directly or via a link to an electronic database, that the amount of total nitrosamines, including both N-nitroso- ribociclib in free or salt form and other nitrosamines, is no more than about 1 ppm. The document may certify, either directly or via a link to an electronic database, that the amount of total nitrosamines, including both N- nitroso-ribociclib in free or salt form and other nitrosamines, is no more than about 0.9 ppm, no more than about 0.8 ppm, no more than about 0.7 ppm, no more than about 0.6 ppm, no more than about 0.5 ppm, no more than about 0.4 ppm, no more than about 0.3 ppm, no more than about 0.2 ppm, no more than about 0.1 ppm, no more than about 0.05 ppm, or no more than about 0.025 ppm. Preferably, another aspect of the invention relates to a pharmaceutical product containing: (a) a pharmaceutical composition comprising ribociclib or a pharmaceutically acceptable salt thereof; and (b) a document which certifies, either directly or via a link to an electronic database, that the amount of total nitrosamines, including both N-nitroso-ribociclib in free or salt form and other nitrosamines, is no more than about 0.7 ppm, for example no more than about 0.6 ppm, relative to the total amount of ribociclib in free or salt form. The pharmaceutical product of the invention may comprise a document which certifies, either directly or via a link to an electronic database, that the amount of total nitrosamines, including both N-nitroso-ribociclib in free or salt form and other nitrosamines, in the composition results in no more than 400 ng / day of said total nitrosamines being administered to the patient, when the composition is administered according to an approved dosage regimen of ribociclib or pharmaceutically acceptable salt thereof. Thus, another aspect of the invention relates to a pharmaceutical product containing: (a) a pharmaceutical composition comprising ribociclib or a pharmaceutically acceptable salt thereof; and (b) a document which certifies, either directly or via a link to an electronic database, that the amount of total nitrosamines, including both N-nitroso-ribociclib in free or salt form and other nitrosamines, present in the composition results in no more than 400 ng / day of total nitrosamines being administered to the patient, when the composition is administered according to an approved dosage regimen of ribociclib or pharmaceutically acceptable salt thereof. PAT059729-WO-PCT03 30 The pharmaceutical product of the invention may comprise a document providing, either directly or via a link to an electronic database, instructions which specify how the composition should be stored, wherein if the composition is stored in accordance with the instructions, then the composition will be substantially free of N- nitroso-ribociclib in free or salt form. The pharmaceutical product of the invention may comprise a document providing, either directly or via a link to an electronic database, instructions which specify how the composition should be stored, wherein if the composition is stored in accordance with the instructions, then the total amount of N-nitroso-ribociclib in free or salt form in the composition will be no more than the maximum amount of nitrosamines that is permitted in such a composition, by a regulatory authority, optionally wherein the total amount of N-nitroso-ribociclib in free or salt form in the composition will be no more than the maximum amount of N-nitroso-ribociclib that is permitted in such a composition, by a regulatory authority. The pharmaceutical product of the invention may comprise a document providing, either directly or via a link to an electronic database, instructions which specify how the composition should be stored, wherein if the composition is stored in accordance with the instructions, then the total amount of N-nitroso-ribociclib in free or salt form in the composition will be no more than 5 ppm, relative to the total amount of ribociclib in free or salt form, for example wherein the total amount of N-nitroso-ribociclib in free or salt form in the composition is or will be no more than about 4 ppm, no more than about 3 ppm, no more than about 2 ppm, no more than about 1 ppm, no more than about 0.9 ppm, no more than about 0.8 ppm, no more than about 0.7 ppm, no more than about 0.65 ppm, no more than about 0.6 ppm, no more than about 0.55 ppm, no more than about 0.5 ppm, no more than about 0.45 ppm, no more than about 0.4 ppm, no more than about 0.35 ppm, no more than about 0.3 ppm, or no more than about 0.25 ppm, relative to the total amount of ribociclib in free or salt form. Preferably, if the composition is stored in accordance with the instructions, then the total amount of N- nitroso-ribociclib in free or salt form is or will be no more than about 1 ppm, no more than about 0.7 ppm, or no more than about 0.6 ppm, relative to the total amount of ribociclib in free or salt form. The document which provides the instructions which specify how the composition should be stored may specify a set of storage conditions comprising a storage time of no more than 60 months, optionally no more than 54, no more than 48, no more than 42, no more than 36, no more than 30, no more than 24, no more than 18, no more than 17, no more than 16, no more than 15, no more than 14, no more than 13, no more than 12, no more than 11, no more than 10, no more than 9, no more than 8, no more than 7, no more than 6, no more than 5, no more than 4, no more than 3, no more than 2, or no more than 1 months and a temperature of nomore than 25 C, optionally wherein the specified temperature is about 2 to about 8 C, or about 20 C to about25 C. Optionally, the instructions specify: (i) a first set of storage conditions; and (ii) a second set of storageconditions for use after the first set of storage conditions. In this embodiment, the first set of storage conditions may comprise a storage time of no more than 60 months, optionally no more than 54, no more than 48, no more than 42, no more than 36, no more than 30, no more than 24, no more than 18, no more than 17, no PAT059729-WO-PCT03 more than 16, no more than 15, no more than 14, no more than 13, no more than 12, or no more than 11months, and a temperature of about 2 to about 8 C, and / or the second set of storage conditions may comprisea storage time of no more than 10 months, optionally no more than 9, no more than 8, no more than 7, no more than 6, no more than 5, no more than 4, no more than 3, no more than 2, or no more than 1 months, anda temperature of no more than 25 C.The pharmaceutical products of the invention may comprise a document providing instructions to a patient as to how to administer the composition. The document which provides the certification as herein described may also be the document which provides the instructions to the patient. Alternatively, the document which provides the certification as described herein may be a separate document from that which provides the instructions. The document which provides the certification may be a component of the packaging of the composition, such as a label, a blister pack, a box, or a carton. A certification via a link to an external database may be e.g., a numerical or alphanumerical identifier, a barcode, or a QR code. An expiry date of the composition, e.g., the end of the shelf life of the composition, may be presented on the document that provides the certification. A plurality of the pharmaceutical products as herein described may be provided, optionally wherein the pharmaceutical products are packaged together. The plurality may comprise at least 5, at least 10, at least 15, at least 20, at least 25, at least 30, at least 35, at least 40, at least 45, at least 50, at least 60, at least 70, at least 80, at least 90, at least 100, at least 150, at least 200, at least 250, at least 300, at least 350, at least 400, at least 450, at least 500, at least 600, at least 700, at least 800, at least 900 or at least 1000 of said pharmaceutical products. One or more (e.g., each) of said pharmaceutical products may comprise one or any combination of: a. a document providing, either directly or via a link to an electronic database, instructions to a patient as to how to administer the composition. The document may be as described herein. b. a document providing, either directly or via a link to an electronic database, instructions which specify how the composition should be stored. The document may be as described herein. c. a document which certifies, either directly or via a link to an electronic database, that the total amount of N-nitroso-ribociclib in free or salt form in the composition is no more than 1 ppm, relative to the total amount of ribociclib in free or salt form. The document may be as described herein. d. a document which indicates that, provided that the composition is stored in accordance with a set of instructions, the total amount of N-nitroso-ribociclib in free or salt form in the composition will be no more than 1 ppm, relative to the total amount of ribociclib in free or salt form. The document may be as described herein. PAT059729-WO-PCT03 32 The pharmaceutical products as herein described may further comprise means to prevent, retard or reduce the formation of N-nitroso-ribociclib in free or salt form in the composition. The means may be one or any combination of the means described herein. For example, the means may be one or any combination of: a. the composition is present in a sealed container under an atmosphere in which the percentage of oxygen is less than 21% by volume, optionally wherein the atmosphere is nitrogen; b. the composition is present in a sealed container which also contains a desiccant; or the composition is present in a sealed pharmaceutical package which also contains a desiccant in a separate container; c. the composition comprises one or more pharmaceutically acceptable additives which prevent, retard or reduce the formation of N-nitroso-ribociclib in free or salt form, optionally wherein each of the one or more additives is selected from the group consisting of pH adjusters, antioxidants, radical scavenging agents, and peroxide-quenching agents; d. the composition is present in a sealed container under an atmosphere in which the relative humidity is less than 75 %, optionally wherein the relative humidity is less than 60 %, and preferably wherein the relative humidity is no more than 15 %, e.g., no more than 2.5 g / kg. For example, in the case of a pharmaceutical product comprising a plurality of oral dosage forms (e.g., a plurality of tablets), then one or any combination of the following may apply: a. the oral dosage forms are each individually or together present in a sealed container under an atmosphere in which the percentage of oxygen is less than 21% by volume, optionally wherein the atmosphere is nitrogen; b. the oral dosage forms are each individually or together present in a sealed container which also contains a desiccant; or the oral dosage forms are together present in a sealed pharmaceutical package which also contains a desiccant in a separate container; c. the oral dosage forms each further comprise one or more pharmaceutically acceptable additives which prevent, retard or reduce the formation of N-nitroso-ribociclib in free or salt form, optionally wherein each of the one or more additives is selected from the group consisting of pH adjusters, antioxidants, radical scavenging agents, and peroxide-quenching agents. Additionally, or alternatively, and preferably in the case of a pharmaceutical product comprising a plurality of oral dosage forms (e.g., a plurality of tablets), the oral dosage forms are packaged within a blister pack such that each oral dosage form is individually packaged within a substantially moisture and / or gas impermeable blister, preferably wherein the humidity of the atmosphere within each blister is no more than 2.5 g / kg. Materials that are substantially moisture and / or gas impermeable and that may be used to provide blister packs are described elsewhere herein. Preferably, the blister pack may be an alu-alu blister pack. Medical uses PAT059729-WO-PCT03 An aspect of the invention provides compositions or pharmaceutical products of the invention for use in methods of therapy. The compositions or pharmaceutical products of the invention may be for use in the treatment of cancer, in particular breast cancer. The methods may comprise administering a therapeutically effective amount of ribociclib or a pharmaceutically acceptable salt thereof in a composition or pharmaceutical product of the invention to a patient in need thereof. The breast cancer may be locally advanced and / or metastatic breast cancer. Metastatic breast cancer (also known as stage 4 breast cancer) refers to breast cancer which has metastasized to other organs in the body. Thus, the compositions and pharmaceutical products of the invention may be for use in the treatment of advanced and / or metastatic breast cancer. Alternatively, the breast cancer may be early breast cancer (EBC). Early breast cancer refers to breast cancer that is contained within the breast, and which may or may not have spread to the lymph nodes in the armpit. Early breast cancer includes stage I, stage II and stage III breast cancer. The compositions and pharmaceutical products of the invention may be particularly useful in the treatment of early breast cancer. The breast cancer may be hormone receptor-positive (HR+) and / or human epidermal growth factor receptor 2-negative (HER2-). The breast cancer may be HR+ / HER2- breast cancer. Thus, the compositions and pharmaceutical products of the invention may be for use in treating HR+ / HER2- breast cancer, optionally HR+ / HER2- advanced and / or metastatic breast cancer or HR+ / HER2- early breast cancer. The compositions and pharmaceutical products of the invention may be particularly useful for treating HR+ / HER2- early breast cancer. An example of advanced breast cancer in the context of this invention is therefore hormone receptor-positive, human epidermal growth factor receptor 2-negative (HR+ / HER2-) locally advanced or metastatic breast cancer. An example of early breast cancer that is particularly relevant in the context of this invention is stage II or III hormone receptor-positive, human epidermal growth factor receptor 2-negative (HR+ / HER2-) early breast cancer. It will be understood by a person skilled in the art that the invention also encompasses a method of treatment, including a method of treating cancer, in particular breast cancer as described herein, by administering to a patient in need thereof a therapeutically effective amount of ribociclib or a pharmaceutically acceptable salt thereof in a composition or pharmaceutical product of the invention. The invention also encompasses a pharmaceutical composition or pharmaceutical product comprising ribociclib or a pharmaceutically acceptable salt thereof for use in therapy, including for use in the treatment of cancer, in particular breast cancer as described herein. The invention also encompasses the use of a composition or pharmaceutical product of the PAT059729-WO-PCT03 34 invention for the manufacture of a medicament for the treatment of a disease, including for the treatment of cancer, in particular breast cancer as described herein. The invention also encompasses the use of a composition or pharmaceutical product of the invention for therapy, including for treating cancer, in particular breast cancer as described herein. Such methods of the invention may be for treating advanced and / or metastatic breast cancer. Alternatively, such methods of the invention may be for treating early breast cancer. Methods of the invention for treating early breast cancer may be particularly useful. The breast cancer may be hormone receptor-positive (HR+) and / or human epidermal growth factor receptor 2-negative (HER2-). The breast cancer may be HR+ and HER2- breast cancer. Thus, the methods of the invention may be for treating HR+ / HER2- breast cancer, optionally HR+ / HER2- advanced and / or metastatic breast cancer or HR+ / HER2- early breast cancer. Methods of the invention for treating HR+ / HER2- early breast cancer may be particularly useful. The patient in need of treatment with the compositions or pharmaceutical products of the invention may be a woman, for example a woman with breast cancer. The patient may be a woman with locally advanced and / or metastatic breast cancer. Alternatively, the patient may be a woman with early breast cancer. The patient may be a woman with HR+ / HER2- breast cancer, for example HR+ / HER2- advanced and / or metastatic breast cancer or HR+ / HER2- early breast cancer. The patient may also be receiving initial endocrine-based therapy, e.g., an aromatase inhibitor or fulvestrant. For example, the compositions or pharmaceutical products of the invention may be administered in combination with an aromatase inhibitor or fulvestrant as initial endocrine-based therapy. Alternatively, the patient may have received prior endocrine therapy. Suitable aromatase inhibitors are letrozole, exemestane or anastrozole. In particular in the context of early breast cancer, the patient may receive ribociclib or a pharmaceutically acceptable salt thereof in combination with endocrine therapy. Examples of suitable combination therapies are provided in WO 2015 / 022609 A1, which is incorporated by reference in its entirety. The patient may be a woman who is pre- or peri-menopausal. In such patients, the initial endocrine-based therapy may be combined with a luteinising hormone-releasing hormone (LHRH) agonist. In the case of oral administration, the daily dose of ribociclib or a pharmaceutically acceptable salt thereof may provide the same amount of ribociclib as a daily dose of about 200 mg to about 600 mg of ribociclib free base. For example, the daily dose of ribociclib or a pharmaceutically acceptable salt thereof may provide the same amount of ribociclib as a daily dose of about 200 mg, about 400 mg, or about 600 mg of ribociclib free base. Preferably, the daily dose of ribociclib or a pharmaceutically acceptable salt thereof may provide the same amount of ribociclib as about 400 mg or about 200 mg, e.g., about 400 mg, of ribociclib free base, in particular PAT059729-WO-PCT03 35 when used in the treatment of early breast cancer as described herein. Alternatively, the daily dose of ribociclib or a pharmaceutically acceptable salt thereof may provide the same amount of ribociclib as about 600 mg, about 400 mg, or about 200 mg, e.g., about 600 mg, of ribociclib free base, in particular when used in the treatment of advanced or metastatic breast cancer as described herein. The mg dose amounts refer to the total daily dose. The total daily dose may be administrated once daily for about 21 consecutive days followed by about 7 days off treatment, resulting in a complete cycle of about 28 days. The treatment may be continued as long as the patient is deriving clinical benefit from therapy or until unacceptable toxicity occurs. The dose may be reduced when toxicity occurs. For example, a dose of 600 mg may be reduced to 400 mg or 200 mg. A dose of 400 mg may be reduced to 200 mg. In the case of oral administration, the compositions of the invention may, as a result of the administration, provide an amount of nitrosamines (such as N-nitroso-ribociclib in free or salt form) to the patient that corresponds to an amount which is no more than about 1500 ng / day of nitrosamine free base (such as N- nitroso-ribociclib free base), for example no more than 400 ng / day, no more than about 300 ng / day, no more than about 200 ng / day, no more than about 100 ng / day, or no more than about 26.5 ng / day. The compositions of the invention may, as a result of their administration, provide an amount of N-nitroso-ribociclib in free or salt form to the patient that corresponds to an amount which is no more than about 400 ng / day of N-nitroso- ribociclib free base, for example no more than about 300 ng / day, no more than about 200 ng / day, no more than about 100 ng / day, or no more than about 26.5 ng / day. The compositions of the invention may, as a result of their administration, provide an amount of total nitrosamines, including both N-nitroso-ribociclib in free or salt form and any other nitrosamines, to the patient that corresponds to an amount which is no more than about 400 ng / day of nitrosamine free base, for example no more than about 300 ng / day, no more than about 200 ng / day, no more than about 100 ng / day, or no more than about 26.5 ng / day. In particular, the compositions of the invention may, as a result of their administration, provide an amount of N-nitroso-ribociclib in free or salt form to the patient that corresponds to an amount which is no more than about 200 ng / day of N-nitroso- ribociclib free base. The patient to be treated may receive, as a result of the administration of the composition in accordance with the treatment, a daily total amount of nitrosamines (such as N-nitroso-ribociclib in free or salt form) that corresponds to an amount of no more than about 400 ng of nitrosamine free base (such as N-nitroso-ribociclib free base), for example of no more than about 300 ng, no more than about 200 ng, no more than about 100 ng, or no more than about 26.5 ng. Thus, the patient to be treated may receive, as a result of the administration of the composition in accordance with the treatment, a daily total amount of N-nitroso-ribociclib in free or salt form that corresponds to an amount of no more than about 400 ng of N-nitroso-ribociclib free base. The patient to be treated may also receive, as a result of the administration of the composition in accordance with the treatment, a daily total amount of total nitrosamines, including both N-nitroso-ribociclib in free or salt form and PAT059729-WO-PCT03 36 any other nitrosamines, that corresponds to an amount of no more than about 400 ng of nitrosamine free base, for example of no more than about 300 ng, no more than about 200 ng, no more than about 100 ng, or no more than about 26.5 ng. Manufacture of the Drug Substance The invention further provides methods of preparing ribociclib or a pharmaceutically acceptable salt thereof which is substantially free of nitrosamines, particularly N-nitroso-ribociclib in free or salt form. While the methods are described separately below, it will be readily apparent to a person of ordinary skill in the art that two or more of these methods may also be used in combination. Thus, the present invention also provides these combined methods of preparing ribociclib or a pharmaceutically acceptable salt thereof. The ribociclib or pharmaceutically acceptable salt thereof produced by these methods may be used in the compositions and pharmaceutical products of the invention as described herein. An aspect of the invention relates to a method wherein (i) the reagents used to prepare the ribociclib or a pharmaceutically acceptable salt thereof and / or (ii) the intermediates used to prepare the ribociclib or a pharmaceutically acceptable salt thereof are independently substantially free of nitrites. An aspect of the invention relates to a method comprising the following deprotection step in which the amount of nitrites in the potassium carbonate is no more than about 5 ppm, for example no more than about 4 ppm, no more than about 3 ppm, no more than about 2 ppm, or no more than about 1 ppm. Preferably, the amount of nitrites in the potassium carbonate is no more than about 1 ppm. The amount of nitrites in the potassium carbonate may optionally be no more than about 0.9 ppm, no more than about 0.8 ppm, no more than about 0.7 ppm, no more than about 0.6 ppm, no more than about 0.5 ppm, no more than about 0.4 ppm, no more than about 0.3 ppm, no more than about 0.2 ppm, no more than about 0.1 ppm, no more than about 0.05 ppm, or no more than about 0.025 ppm. Manufacture of a pharmaceutically acceptable salt of ribociclib An aspect of the invention relates to a method of preparing a pharmaceutically acceptable salt of ribociclib which comprises using a ribociclib free base which is substantially free of nitrites. For example, the amount of nitrites in the ribociclib free base may be no more than about 5 ppm, for example no more than about 4 ppm, no more than about 3 ppm, no more than about 2 ppm, no more than about 1 ppm, no more than about 0.5 ppm, no more than about 0.25 ppm, no more than about 0.1 ppm, less than about 0.1 ppm, less than about PAT059729-WO-PCT03 37 0.05 ppm, or less than about 0.025 ppm. Preferably, the amount of nitrites in the ribociclib free base is less than about 0.1 ppm. The method may comprise forming the salt under acidic conditions. For example, organic or inorganic acids may be reacted with the ribociclib base. Suitable inorganic acids are, for example, halogen acids, such as hydrochloric acid, sulfuric acid, or phosphoric acid. Suitable organic acids are, e.g., succinic acid, carboxylic acids or sulfonic acid, such as fumaric acid or methanesulfonic acid. The organic or inorganic acid used may be substantially free of nitrites. For example, the amount of nitrites in the organic or inorganic acid (such as succinic acid) may be no more than about 5 ppm, for example no more than about 4 ppm, no more than about 3 ppm, no more than about 2 ppm, or no more than about 1 ppm. Preferably, the amount of nitrites in the organic or inorganic acid (such as succinic acid) is no more than about 1 ppm. The amount of nitrites in the organic or inorganic acid (such as succinic acid) may be no more than about 0.5 ppm, no more than about 0.25 ppm, no more than about 0.1 ppm, less than about 0.1 ppm, less than about 0.05 ppm, or less than about 0.025 ppm. In certain embodiments, the amount of nitrites in the ribociclib free base and the amount of nitrites in the organic or inorganic acid (such as succinic acid) may each be no more than about 5 ppm, for example no more than about 4 ppm, no more than about 3 ppm, no more than about 2 ppm, no more than about 1 ppm, no more than about 0.5 ppm, no more than about 0.25 ppm, no more than about 0.1 ppm, less than about 0.1 ppm, less than about 0.05 ppm, or less than about 0.025 ppm. As disclosed elsewhere herein, the amount of nitrites in a composition, e.g., the amount of nitrites in the ribociclib free base and / or the amount of nitrites in the organic or inorganic acid (such as succinic acid) may be determined using the Griess test. Accordingly, the invention provides a method of preparing ribociclib or a pharmaceutically acceptable salt thereof, wherein the method comprises the use of the Griess test to determine the amount of nitrites in a composition comprising ribociclib free base and / or the amount of nitrites in an organic or inorganic acid (such as succinic acid). Solvent oxygen content An aspect of the invention relates to a method of preparing ribociclib or a pharmaceutically acceptable salt thereof with an acid, wherein the method comprises the use of one or more solvents which, immediately prior to their use in the method, are stored under an atmosphere in which the percentage of oxygen is less than 21% by volume. The method may comprise the use of said one or more solvents for dissolving ribociclib and / or said acid. Furthermore, the method may be for preparing a pharmaceutically acceptable salt of ribociclib with an acid, wherein the method comprises the use of said one or more solvents for dissolving ribociclib and said acid, respectively, prior to their combination to form the pharmaceutically acceptable salt of ribociclib. Thus, an PAT059729-WO-PCT03 38 aspect of the invention relates to a method of preparing ribociclib or a pharmaceutically acceptable salt thereof with an acid, wherein the method comprises: (a) obtaining one or more solvents, where the one or more solvents are contained in a sealed container under an atmosphere in which the percentage of oxygen is less than 21% by volume; and (b) using the one or more solvents to dissolve ribociclib and / or said acid. Preferably, the one or more solvents are used shortly after, such as immediately after, the sealed container is unsealed, e.g., within 12 hours, within 9 hours, within 6 hours, or within 3 hours. The atmosphere may be an inert gas such as helium, nitrogen, argon, or neon. Preferably, the atmosphere is nitrogen. The one or more solvents may be substantially free of nitrites. The total amount of nitrites in each of the one or more solvents may be no more than about 5 ppb, relative to the amount of the respective solvent, for example no more than about 4 ppb, no more than about 3.5 ppb, no more than about 3 ppb, no more than about 2.5 ppb, no more than about 2 ppb, no more than about 1.5 ppb, no more than about 1 ppb, or no more than about 0.5 ppb, relative to the amount of the respective solvent. Preferably, the total amount of nitrites in each of the one or more solvents may be no more than about 5 ppb, no more than about 3.5 ppb, or no more than about 1 ppb, relative to the amount of the respective solvent. More preferably, the total amount of nitrites in each of the one or more solvents may be no more than about 1 ppb, relative to the amount of the respective solvent. Where there is more than one solvent, the combined total amount of nitrites in the solvents may be no more than about 5 ppb, relative to the combined amount of the solvents, for example no more than about 4 ppb, no more than about 3.5 ppb, no more than about 3 ppb, no more than about 2.5 ppb, no more than about 2 ppb, no more than about 1.5 ppb, no more than about 1 ppb, or no more than about 0.5 ppb, relative to the combined amount of the solvents. Preferably, the combined total amount of nitrites in the solvents may be no more than about 5 ppb, no more than about 3.5 ppb, or no more than about 1 ppb, relative to the combined amount of the solvents. More preferably, the combined total amount of nitrites in the solvents may be no more than about 1 ppb, relative to the combined amount of the solvents. As disclosed elsewhere herein, the amount of nitrites in a composition, e.g., the amount of nitrites in each of the one or more solvents, may be determined using the Griess test. Accordingly, the invention provides a method of preparing a composition comprising ribociclib or a pharmaceutically acceptable salt thereof, wherein the method comprises the use of the Griess test to determine the amount of nitrites in each of one or more solvents that are used in the method. The one or more solvents may be isopropanol, n-propanol, methyl tert-butyl ether, ethyl acetate, isopropyl acetate, or ethanol. The one or more solvents may be or may comprise isopropanol, optionally wherein the isopropanol is substantially free of isopropyl nitrite, e.g., the amount of isopropyl nitrite in the isopropanol is no PAT059729-WO-PCT03 39 more than one of the individual values presented above for the total amount of nitrites in each of the one or more solvents, e.g., preferably less than about 1 ppb. By way of example, the one or more solvents may be or may comprise isopropanol and water, for example the one or more solvents may be or may comprise a solvent mixture of isopropanol and water with at least 10%, at least 20 vol%, at least 30 vol%, at least 40 vol%, at least 50 vol%, at least 60 vol%, and preferably at least 70 vol% isopropanol. Preferably, the solvent consists of isopropanol. Alternatively, the one or more solvents may not be or may not comprise isopropanol. Solvent distillation Another aspect of the invention relates to a method of preparing ribociclib or a pharmaceutically acceptable salt thereof, wherein the method comprises the use of one or more solvents, and wherein the method comprises distilling said one or more solvents to reduce their content of nitrites, prior to their use. Accordingly, the invention also provides a method of preparing ribociclib or a pharmaceutically acceptable salt thereof, wherein the method comprises distilling one or more solvents to reduce their content of nitrites. The ribociclib or a pharmaceutically acceptable salt thereof may be prepared using an acid. The method of preparation may comprise the use of one or more solvents for dissolving ribociclib and / or said acid, and the method may comprise distilling the one or more solvents to reduce their content of nitrites, prior to said use. Thus, an aspect of the invention relates to a method of preparing ribociclib or a pharmaceutically acceptable salt thereof with an acid, wherein the method comprises the use of one or more solvents for dissolving ribociclib and / or said acid, and wherein the method comprises distilling the one or more solvents to reduce their content of nitrites, prior to said use. The ribociclib or a pharmaceutically acceptable salt thereof may be prepared using an acid and the method of preparation may comprise: (a) obtaining one or more solvents, (b) distilling said one or more solvents to reduce their content of nitrites; and (c) using the one or more distilled solvents to dissolve ribociclib and / or said acid. Thus, another aspect of the invention relates to a method of preparing ribociclib or a pharmaceutically acceptable salt thereof with an acid, wherein the method comprises: (a) obtaining one or more solvents; (b) distilling said one or more solvents to reduce their content of nitrites; and (c) using the one or more distilled solvents to dissolve ribociclib and / or said acid. The one or more solvents, prior to and / or after distillation, may be contained in a sealed container under an atmosphere in which the percentage of oxygen is less than 21% by volume. The atmosphere may be an inert gas such as helium, nitrogen, argon, or neon. Preferably, the atmosphere is nitrogen. The total amount of nitrites in the or each solvent, following the distillation, may be no more than about 5 ppb, relative to the amount of the respective solvent, for example no more than about 4 ppb, no more than about 3.5 ppb, no more than about 3 ppb, no more than about 2.5 ppb, no more than about 2 ppb, no more than about 1.5 ppb, no more than about 1 ppb, or no more than about 0.5 ppb, relative to the amount of the PAT059729-WO-PCT03 40 respective solvent. Preferably, the total amount of nitrites in the or each solvent, following the distillation, may be no more than about 5 ppb, no more than about 3.5 ppb, no more than about 1 ppb, or less than about 1 ppb, relative to the amount of the respective solvent. More preferably, the total amount of nitrites in the or each solvent, following the distillation, may be no more than about 1 ppb, relative to the amount of the respective solvent. Where there is more than one solvent, the combined total amount of nitrites in the solvents, following the distillation, may be no more than about 5 ppb, relative to the combined amount of the solvents, for example no more than about 4 ppb, no more than about 3.5 ppb, no more than about 3 ppb, no more than about 2.5 ppb, no more than about 2 ppb, no more than about 1.5 ppb, no more than about 1 ppb, or no more than about 0.5 ppb, relative to the combined amount of the solvents. Preferably, the combined total amount of nitrites in the solvents, following the distillation, may be no more than about 5 ppb, no more than about 3.5 ppb, or no more than about 1 ppb, relative to the combined amount of the solvents. More preferably, the combined total amount of nitrites in the solvents, following the distillation, may be no more than about 1 ppb, relative to the combined amount of the solvents. The distillation may reduce the total amount of nitrites in the one or more solvents, e.g., in each of the solvents that are distilled, by at least 5%, at least 10%, at least 15%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, or at least 70%, relative to the total amount of nitrites in the solvent(s) prior to the distillation. Where there is more than one solvent, the distillation may reduce the combined total amount of nitrites in the solvents that are distilled by at least 5%, at least 10%, at least 15%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, or at least 70%, relative to the combined total amount of nitrites in the solvents prior to the distillation. The one or more solvents, following the distillation, may be substantially free of nitrites. The total amount of nitrites in each of the one or more solvents may be no more than about 5 ppb, for example no more than about 4 ppb, no more than about 3.5 ppb, no more than about 3 ppb, no more than about 2.5 ppb, no more than about 2 ppb, no more than about 1.5 ppb, no more than about 1 ppb, or no more than about 0.5 ppb. Preferably, the total amount of nitrites in each of the one or more solvents may be no more than about 5 ppb, no more than about 3.5 ppb, no more than about 1 ppb, or less than about 1 ppb. More preferably, the total amount of nitrites in each of the one or more solvents may be less than about 1 ppb. Where there is more than one solvent, the combined total amount of nitrites in the solvents may be no more than about 5 ppb, relative to the combined amount of the solvents, for example no more than about 4 ppb, no more than about 3.5 ppb, no more than about 3 ppb, no more than about 2.5 ppb, no more than about 2 ppb, no more than about 1.5 ppb, no more than about 1 ppb, or no more than about 0.5 ppb. Preferably, the combined total amount of nitrites in the solvents may be no more than about 5 ppb, no more than about 3.5 PAT059729-WO-PCT03 41 ppb, or no more than about 1 ppb. More preferably, the combined total amount of nitrites in the solvents may be no more than about 1 ppb. As disclosed elsewhere herein, the amount of nitrites in a composition, e.g., the amount of nitrites in a solvent prior to and / or following its distillation, may be determined using the Griess test. Accordingly, the invention provides a method of preparing a composition comprising ribociclib or a pharmaceutically acceptable salt thereof, wherein the method comprises the use of the Griess test to determine the amount of nitrites in each of one or more solvents that are used in the method, prior to and / or following their distillation. The one or more solvents may be isopropanol, n-propanol, methyl tert-butyl ether, ethyl acetate, isopropyl acetate, or ethanol. The one or more solvents may be or may comprise isopropanol, optionally wherein the isopropanol is (i.e., becomes as a result of the distillation, or having fulfilled the criterion before the distillation is also compliant with the criterion after the distillation) substantially free of isopropyl nitrite, e.g., the amount of isopropyl nitrite in the isopropanol is no more than one of the individual values presented above for the total amount of nitrites in the one or more solvents, e.g., preferably no more than 1 ppb. By way of example, the one or more solvents may be or may comprise isopropanol and water, for example the one or more solvents may be or may comprise a solvent mixture of isopropanol and water with at least 10%, at least 20 vol%, at least 30 vol%, at least 40 vol%, at least 50 vol%, at least 60 vol%, and preferably at least 70 vol% isopropanol. Preferably, the solvent consists of isopropanol. Alternatively, the one or more solvents may not be or may not comprise isopropanol. The distillation may be over and / or through ascorbic acid, preferably over ascorbic acid. Ascorbic acid 10% may be used. Following the distillation, the method may further comprise: (a) testing different fractions of the distillate for the presence and / or total amount of nitrites; (b) identifying the fraction(s) with the lowest amount of nitrites; and (c) using said fraction(s) with the lowest amount of nitrites as the one or more distilled solvents in the step of dissolving the ribociclib and / or said acid. Dissolving ribociclib and / or said acid using the one or more distilled solvents may be performed by mixing the ribociclib and / or said acid with the one or more distilled solvents. The mixing may be performed by adding the components to a mixing vessel. The (i) ribociclib and / or said acid and the (ii) one or more distilled solvents may be added to the mixing vessel simultaneously, or they may be added subsequently, in any order. The ribociclib and / or said acid may be added last to the mixing vessel. The one or more distilled solvents may be added first to the mixing vessel, and the ribociclib and / or said acid may be added subsequently to the mixing vessel. Ion exchange resins PAT059729-WO-PCT03 42 Another aspect of the invention relates to a method of preparing ribociclib or a pharmaceutically acceptable salt thereof, wherein the method comprises the use of one or more solvents, and wherein the method comprises passing said one or more solvents through an ion exchange resin that is capable of adsorbing nitrites. Accordingly, the invention also provides a method of preparing ribociclib or a pharmaceutically acceptable salt thereof, wherein the method comprises passing one or more solvents through an ion exchange resin that is capable of adsorbing nitrites. Another aspect of the invention relates to a method of preparing a pharmaceutically acceptable salt of ribociclib with an acid, wherein the method comprises mixing a first solution of ribociclib with a second solution of said acid. The mixing of the first and second solutions may be performed by adding the two solutions to a mixing vessel. The first and second solutions may be added to the mixing vessel simultaneously, or may be added subsequently, in any order. Preferably, the first solution (i.e., of ribociclib) may be added last to the mixing vessel. Thus, in some aspects, the second solution (i.e., of the acid) is added first to the mixing vessel, and the first solution (i.e., of ribociclib) is added subsequently to the mixing vessel. The method may comprise one or more steps of reducing the content of nitrites in said first and / or second solutions, prior to their combination. The one or more steps may involve passing the first and / or second solutions through an ion exchange resin that is capable of adsorbing nitrites. The preparation method may comprise the use of one or more solvents for dissolving ribociclib and / or dissolving an acid that will be used to make a pharmaceutically acceptable salt of ribociclib. The method may further comprise passing the one or more solvents through an ion exchange resin which is capable of adsorbing nitrites, prior to said use. Thus, an aspect of the invention relates to a method of preparing ribociclib or a pharmaceutically acceptable salt thereof with an acid, wherein the method comprises the use of one or more solvents for dissolving ribociclib and / or said acid, and wherein the method comprises passing the one or more solvents through an ion exchange resin which is capable of adsorbing nitrites, prior to said use. The method may further comprise: (a) distilling the one or more solvents to reduce their content of nitrites; and (b) passing the one or more distilled solvents through said ion exchange resin. Alternatively, the method may further comprise: (a) passing the one or more solvents through said ion exchange resin; and (b) distilling the one or more solvents to reduce their content of nitrites. Accordingly, the step of passing the one or more solvents through an ion exchange resin may occur before, after, or both before and after the step of distillation. The method of preparation may comprise a step of passing a solution comprising or consisting of: (a) ribociclib or a pharmaceutically acceptable salt thereof; and (b) a solvent, through an ion exchange resin that is capable of adsorbing nitrites from the solution. Thus, another aspect of the invention relates to a method of preparing ribociclib or a pharmaceutically acceptable salt thereof with an acid, wherein the method comprises a step of PAT059729-WO-PCT03 43 passing a solution comprising or consisting of: (a) ribociclib or a pharmaceutically acceptable salt thereof; and (b) a solvent, through an ion exchange resin that is capable of adsorbing nitrites from the solution. A pharmaceutically acceptable salt of ribociclib may be prepared with an acid and the method of preparation may comprise a step of passing a solution comprising or consisting of: (a) said acid; and (b) a solvent, through an ion exchange resin that is capable of adsorbing nitrites from the solution. Thus, an aspect of the invention relates to a method of preparing a pharmaceutically acceptable salt of ribociclib with an acid, wherein the method comprises a step of passing a solution comprising or consisting of: (a) said acid; and (b) a solvent, through an ion exchange resin that is capable of adsorbing nitrites from the solution. The method may further comprise one or more of the following steps: (a) obtaining one or more solvents; (b) distilling the one or more solvents to reduce their content of nitrites; and (c) using the one or more distilled solvents to dissolve ribociclib and / or said acid. The distillation may be over and / or through ascorbic acid, preferably over ascorbic acid. Preferably, the method comprises all of steps (a)-(c). The method may further comprise: (d) passing the solution of ribociclib and / or the solution of said acid through an ion exchange resin that is capable of adsorbing nitrites from a solution. Alternatively, the method may further comprise one or more of the following steps: (a) obtaining one or more solvents; (b) passing the one or more solvents through an ion exchange resin that is capable of adsorbing nitrites from a solution, and (c) using the one or more solvents to dissolve ribociclib and / or said acid. The method may further comprise (d) distilling the one or more solvents to reduce their content of nitrites, either before or after step (b). The distillation may be over and / or through ascorbic acid, preferably over ascorbic acid. Preferably, the method comprises all of steps (a)-(d), for example in the order (a), (b), (d) and (c), or in the order (a), (d), (b) and (c). The ion exchange resin that is capable of adsorbing nitrites for use in the methods described herein may adsorb no more than 5% by weight of the total amount of ribociclib in free or salt form. The ion exchange resin may adsorb no more than 4%, no more than 3%, no more than 2%, or no more than 1% by weight of said ribociclib in free or salt form. The ion exchange resin that is capable of adsorbing nitrites for use in the methods described herein may be selected from the group consisting of an activated charcoal resin, a silica gel resin, a celite resin, or an aluminium oxide resin. The ion exchange resin that is capable of adsorbing nitrites for use in the methods described herein may be a silica gel resin, a celite resin, or an aluminium oxide resin. In one embodiment, the functional group of the ion exchange resin is an organic acid with ammonium ion, e.g., sulfonic acid with ammonium ion, e.g., AmberLiteTMMB. In one embodiment, the ion exchange resin is AmberLiteTMIRA-402. In one embodiment, the ion exchange resin is an activated charcoal resin, optionally having the composition of any one of activated charcoal resins 1-47 in Example 3 below. PAT059729-WO-PCT03 The ion exchange resin is preferably a basic resin or a mixed bed resin containing both cationic and ion exchange functional groups on its surface. Preferably, the ion exchange resin contains a quaternary ammonium, as shown in the structure below in the case of the ion exchange resin AmberLiteTMIRA-402: In such resins, the counterion associated with the quaternary ammonium (Cl- in the above resin) will be replaced by nitrite in the solution that is being passed through the ion exchange resin. Following passage through the ion exchange resin, the one or more solvents may be substantially free of nitrites. The total amount of nitrites in the or each solvent may be no more than about 5 ppb, relative to the amount of the respective solvent, for example no more than about 4 ppb, no more than about 3.5 ppb, no more than about 3 ppb, no more than about 2.5 ppb, no more than about 2 ppb, no more than about 1.5 ppb, no more than about 1 ppb, less than about 1 ppb, or no more than about 0.5 ppb, relative to the amount of the respective solvent. Preferably, the total amount of nitrites in the or each solvent may be no more than about 5 ppb, no more than about 3.5 ppb, or no more than about 1 ppb, relative to the amount of the respective solvent. More preferably, the total amount of nitrites in the or each solvent may be no more than about 1 ppb, relative to the amount of the respective solvent. In one aspect, in which the one or more solvents is more than one solvent, the combined total amount of nitrites in the solvents, following passage through the ion exchange resin, may be no more than about 5 ppb, relative to the combined amount of the solvents, for example no more than about 4 ppb, no more than about 3.5 ppb, no more than about 3 ppb, no more than about 2.5 ppb, no more than about 2 ppb, no more than about 1.5 ppb, no more than about 1 ppb, or no more than about 0.5 ppb, relative to the combined amount of the solvents. Preferably, the combined total amount of nitrites in the solvents, following passage through the ion exchange resin, may be no more than about 5 ppb, no more than about 3.5 ppb, or no more than about 1 ppb, relative to the combined amount of the solvents. More preferably, the combined total amount of nitrites in the solvents, following passage through the ion exchange resin may be no more than about 1 ppb, relative to the combined amount of the solvents. PAT059729-WO-PCT03 45 As disclosed elsewhere herein, the amount of nitrites in a composition, e.g., the amount of nitrites in a solvent prior to and / or following its passage through an ion exchange resin that is capable of absorbing nitrites, may be determined using the Griess test. Thus, the invention provides a method of preparing a composition comprising ribociclib or a pharmaceutically acceptable salt thereof, wherein the method comprises the use of the Griess test to determine the amount of nitrites in each of one or more solvents that are used in the method, prior to and / or following their passage through an ion exchange resin that is capable of absorbing nitrites. The one or more solvents may be isopropanol, n-propanol, methyl tert-butyl ether, ethyl acetate, isopropyl acetate, and / or ethanol. The one or more solvents may be or may comprise isopropanol, optionally wherein the isopropanol is (i.e., becomes as a result of its passage through the ion exchange resin, or having fulfilled the criterion before its passage through the ion exchange resin is also compliant with the criterion after said passage) substantially free of isopropyl nitrite, e.g., the amount of isopropyl nitrite in the isopropanol is no more than one of the individual values presented above for the total amount of nitrites in the or each solvent, e.g., preferably no more than 1 ppb. By way of example, the one or more solvents may be or may comprise isopropanol and water, for example the one or more solvents may be or may comprise a solvent mixture of isopropanol and water with at least 10%, at least 20 vol%, at least 30 vol%, at least 40 vol%, at least 50 vol%, at least 60 vol%, and preferably at least 70 vol% isopropanol. Preferably, the solvent consists of isopropanol. Alternatively, the one or more solvents may not be or may not comprise isopropanol. The one or more solvents that are used in the methods described herein may, prior to and / or after passage through the ion exchange resin, be contained in a sealed container under an atmosphere in which the percentage of oxygen is less than 21% by volume. The atmosphere may be an inert gas such as helium, nitrogen, argon, or neon. Preferably, the atmosphere is nitrogen. The distillation of the one or more solvents may be over and / or through ascorbic acid, preferably over ascorbic acid. Use of filters Another aspect of the invention relates to a method of preparing ribociclib or a pharmaceutically acceptable salt thereof with an acid, wherein the method comprises the use of one or more filters which do not comprise a nitrocellulose membrane. In some aspects, none of the filters that are used in the method comprises a nitrocellulose membrane. The one or more filters may be used to filter a solution of ribociclib and / or a solution of said acid. For example, an aspect of the invention relates to a method of preparing ribociclib or a pharmaceutically acceptable salt thereof with an acid, wherein the method comprises: (a) obtaining a solution of ribociclib and / or a solution of said acid; and (b) filtering the or each solution with a filter that does not comprise a nitrocellulose membrane. The or each filter may be a metal filter, preferably a stainless steel filter. PAT059729-WO-PCT03 The method may comprise the use of one or more carbon filters and one or more polishing filters, wherein the filters do not comprise a nitrocellulose membrane. In some aspects of the method, none of the carbon or polishing filters comprises a nitrocellulose membrane. The or each polishing filter may be a metal filter, preferably a stainless steel filter. For example, the method of preparing a pharmaceutically acceptable salt of ribociclib may comprise a salt formation step, wherein the salt formation step comprises the use of one carbon filter and two polishing filters, wherein the filters do not comprise a nitrocellulose membrane, optionally wherein none of the carbon or polishing filters comprises a nitrocellulose membrane. If a carbon filter is used, a charcoal treatment step may be implemented prior to use of the carbon filter. The filtration step(s) may each be carried out at a temperature of about 60°C to about 90°C, or about 70 to about 80°C, or about 75°C. The method may comprise filtering a solution of acid (such as succinic acid) with a filter of about 10 to 50 inches, such as about 30 inches. The method may comprise filtering a solution of acid (such as succinic acid) with a filter having a mesh size of about 0.1 to 1.0 μm, such as about 0.5 μm. Washing of the crystalline salt Another aspect of the invention relates to a method of preparing a crystalline form of ribociclib or a pharmaceutically acceptable salt thereof, wherein the method comprises washing the crystalline form with a solvent. The pharmaceutically acceptable salt of ribociclib may be ribociclib succinate. Thus, an aspect of the invention relates to a method of preparing ribociclib succinate, wherein the method comprises: (a) preparing a crystalline form of ribociclib succinate; and (b) washing the crystalline form with a solvent. The washing has the effect of reducing the total amount of nitrosamines (such as the total amount of N-nitroso-ribociclib in free or salt form) within the crystalline form. The solvent may be substantially free of nitrites. The total amount of nitrites in the solvent may be no more than about 5 ppb, relative to the amount of the solvent, for example no more than about 4 ppb, no more than about 3.5 ppb, no more than about 3 ppb, no more than about 2.5 ppb, no more than about 2 ppb, no more than about 1.5 ppb, no more than about 1 ppb, or no more than about 0.5 ppb, relative to the amount of the respective solvent. Preferably, the total amount of nitrites in the solvent may be no more than about 5 ppb, no more than about 3.5 ppb, or no more than about 1 ppb, relative to the amount of the solvent. More preferably, the total amount of nitrites in the solvent may be no more than about 1 ppb, relative to the amount of the solvent. The solvent may be isopropanol, n-propanol, methyl tert-butyl ether, ethyl acetate, isopropyl acetate, or ethanol. The solvent may be isopropanol or ethanol, optionally wherein the isopropanol is substantially free of isopropyl nitrite, e.g., the amount of isopropyl nitrite in the isopropanol is no more than one of the individual values presented above for the total amount of nitrites in the solvent, e.g., preferably no more than 1 ppb. By PAT059729-WO-PCT03 47 way of example, the one or more solvents may be or may comprise isopropanol and water, for example the one or more solvents may be or may comprise a solvent mixture of isopropanol and water with at least 10%, at least 20 vol%, at least 30 vol%, at least 40 vol%, at least 50 vol%, at least 60 vol%, and preferably at least 70 vol% isopropanol. The solvent may consist of isopropanol. Preferably, the solvent is ethanol. The washing step (b) may be carried out at a temperature of less than about 30°C, or less than about 25°C, or less than about 20°C, or less than about 15°C, such as about 10°C. The washing step (b) may be repeated multiple times, such as two times or three times. Manufacture of the Drug Product The invention further provides methods of preparing a pharmaceutical composition comprising (i) ribociclib or a pharmaceutically acceptable salt thereof and (ii) one or more pharmaceutically acceptable excipients, wherein the pharmaceutical composition is substantially free of nitrosamines, particularly N-nitroso-ribociclib in free or salt form. While methods of preparing such pharmaceutical compositions are described separately below, it will be readily apparent to a person of ordinary skill in the art that two or more of these methods may also be used in combination. Thus, the present invention also provides the combined methods of preparing a pharmaceutical composition comprising (i) ribociclib or a pharmaceutically acceptable salt thereof and (ii) one or more pharmaceutically acceptable excipients, wherein the pharmaceutical composition is substantially free of nitrosamines, particularly N-nitroso-ribociclib in free or salt form. The pharmaceutical compositions produced by these methods may be used in the pharmaceutical products described herein. Thus, an aspect of the invention relates to a method of preparing a pharmaceutical composition comprising mixing ribociclib or a pharmaceutically acceptable salt thereof with one or more pharmaceutically acceptable excipients, wherein the one or more pharmaceutically acceptable excipients, and optionally each of the one or more pharmaceutically acceptable excipients, has a content of nitrites of no more than 5 ppm, for example no more than 4 ppm, no more than 3 ppm, no more than 2 ppm, no more than 1 ppm, or less than about 0.5 ppm. The one or more pharmaceutically acceptable excipients, e.g., each of the one or more pharmaceutically acceptable excipients, may have a content of nitrites of less than about 0.4 ppm, less than about 0.3 ppm, less than about 0.2 ppm, or less than about 0.1 ppm. It will be appreciated by a person of ordinary skill in the art that references herein to mixing two or more components may alternatively be expressed as combining said two or more components. Accordingly, the invention provides a method of preparing a pharmaceutical composition comprising mixing ribociclib or a pharmaceutically acceptable salt thereof with one or more pharmaceutically acceptable excipients, wherein each of the one or more pharmaceutically acceptable excipients has a content of nitrites of no more than 5 ppm, for example no more than 4 ppm, no more than 3 ppm, no more than 2 ppm, no more than 1 ppm, or less than about 0.5 ppm, relative to the amount of the respective excipient. Each of the one or PAT059729-WO-PCT03 48 more pharmaceutically acceptable excipients may have a content of nitrites of less than about 0.4 ppm, less than about 0.3 ppm, less than about 0.2 ppm, or less than about 0.1 ppm, relative to the amount of the respective excipient. Another aspect of the invention relates to a method of preparing a pharmaceutical composition comprising mixing ribociclib or a pharmaceutically acceptable salt thereof with more than one pharmaceutically acceptable excipient, wherein the combined excipients have a total content of nitrites of no more than 5 ppm, for example no more than 4 ppm, no more than 3 ppm, no more than 2 ppm, no more than 1 ppm, or less than about 0.5 ppm, relative to the combined amount of the excipients. The combined excipients may have a total content of nitrites of less than about 0.4 ppm, less than about 0.3 ppm, less than about 0.2 ppm, or less than about 0.1 ppm, relative to the combined amount of the excipients. Any of the pharmaceutical compositions as described herein which comprise or consist of (i) ribociclib or a pharmaceutically acceptable salt thereof and (ii) one or more pharmaceutically acceptable excipients, regardless of the method by which those compositions are prepared, may have a total content of nitrites as described herein, for example a total content of nitrites of no more than 5 ppm, no more than 4 ppm, no more than 3 ppm, no more than 2 ppm, no more than 1 ppm, or no more than 0.5 ppm, preferably wherein the total content of nitrites is no more than 0.4 ppm, no more than 0.3 ppm, no more than 0.2 ppm, no more than 0.1 ppm, no more than 0.05 ppm, or no more than 0.025 ppm. Such a pharmaceutical composition may be an oral dosage form, such as a tablet, e.g., a film-coated tablet. As would be understood by a person of ordinary skill in the art, these ppm values for the content of nitrites in a pharmaceutical composition should take account of all of the components of the composition. Pharmaceutical compositions of the invention having reduced concentrations of nitrites are further described elsewhere herein. They may be included within the pharmaceutical products of the invention, e.g., they may be provided as a plurality of oral dosage forms, e.g., a plurality of tablets, optionally wherein the tablets are packaged in a blister pack as described elsewhere herein, more preferably such that each tablet is individually packaged within a substantially moisture and / or gas impermeable blister, such as within a substantially moisture and / or gas impermeable blister as described elsewhere herein, preferably an alu-alu blister. The method of preparing a pharmaceutical composition comprising ribociclib or a pharmaceutically acceptable salt thereof, and one or more pharmaceutically acceptable excipients, may comprise a step of mixing ribociclib or said pharmaceutically acceptable salt thereof with the one or more pharmaceutically acceptable excipients. The method may further comprise a step of drying the resulting mixture. Thus, an aspect of the invention relates to a method of preparing a pharmaceutical composition comprising (i) ribociclib or a pharmaceutically acceptable salt thereof; and (ii) one or more pharmaceutically acceptable excipients, wherein the method comprises: (a) mixing ribociclib or said pharmaceutically acceptable salt thereof with the one or more excipients; and (b) drying the resulting mixture. The drying step may be carried out until the water activity value becomes less than 0.12, less than 0.10, less than 0.09 or less than 0.08, preferably wherein the water activity PAT059729-WO-PCT03 49 level becomes no more than 0.06, and more preferably no more than 0.05. The method may further comprise, either before or after the step of drying, a step of processing the composition into a solid oral dosage form. For example, the method may comprise a further step of compressing the composition into a tablet. Preferably, the step of compressing the composition into a tablet is before the step of drying. Thus, the invention provides a method of preparing a pharmaceutical composition comprising: (i) ribociclib or a pharmaceutically acceptable salt thereof; and (ii) one or more pharmaceutically acceptable excipients, wherein the method comprises: (a) providing the composition; (b) compressing the composition into one or more tablets; and (c) drying the tablet(s) until the water activity value of the tablet(s) is less than 0.08, preferably wherein the water activity value is no more than 0.06, and more preferably no more than 0.05. Alternatively, the method may comprise a further step of filling the composition into a capsule. The method may comprise, after the step of drying, a further step of storing the composition in the presence of a desiccant, as described elsewhere herein, e.g., storing the composition in a sealed container which also contains a desiccant, or storing the composition in a sealed pharmaceutical package which also contains a desiccant in a separate container. The one or more pharmaceutically acceptable excipients may be selected from the group consisting of magnesium stearate, microcrystalline cellulose, crospovidone, hydroxypropyl cellulose and silica. Preferably, the pharmaceutical composition comprises more than one pharmaceutically acceptable excipient. Preferably, the pharmaceutical composition comprises magnesium stearate, microcrystalline cellulose, crospovidone, hydroxypropyl cellulose and silica. In the case where the pharmaceutical product is a tablet, the tablet may be coated or uncoated. In an uncoated tablet, the tablet core is the whole tablet. In a coated tablet, the tablet core is the portion of the tablet excluding the coating. In the case where the pharmaceutical product is a tablet, the tablet core may comprise or consist of (i) ribociclib or a pharmaceutically acceptable salt thereof, and (ii) one or more pharmaceutically acceptable excipients. The tablet core may comprise or consist of (i) ribociclib or a pharmaceutically acceptable salt thereof, and (ii) one or more pharmaceutically acceptable excipients selected from the group consisting of magnesium stearate, microcrystalline cellulose, crospovidone, hydroxypropyl cellulose and silica. Preferably, the tablet core comprises or consists of ribociclib succinate, magnesium stearate, microcrystalline cellulose, crospovidone, hydroxypropyl cellulose and silica. A tablet comprising ribociclib succinate may have a drug load of at least 20%, at least, 25%, at least 30%, at least 35%, at least 40%, at least 45%, at least 50% or at least 55% when measured in w / w percentage of the ribociclib succinate of the tablet core. The % of ribociclib succinate (w / w) may be at least 40%, at least 50% PAT059729-WO-PCT03 50 or at least 55% of the tablet core. The % of ribociclib succinate (w / w) may be from about 55% to about 65% of the tablet core. The % of ribociclib succinate (w / w) may be about 59% of the tablet core. A tablet comprising ribociclib free base may have a drug load of at least 32%, at least 40%, or at least 44%, when measured in w / w percentage of the ribociclib free base of the tablet core. The % of ribociclib free base (w / w) may be at least 32%, at least 40%, at least 44%, at least 47% or at least 52% of the tablet core. The % of ribociclib free base (w / w) may be from about 44% to about 52% of the tablet core. The % of ribociclib free base (w / w) may be about 47% of the tablet core. The tablet core may comprise or consist of from about 59 wt% of ribociclib succinate, about 4 wt% magnesium stearate, about 16 wt% microcrystalline cellulose, about 10 wt% crospovidone, about 11 wt% hydroxypropyl cellulose and about 1wt % silica, wherein the wt% are each defined relative to the weight of the tablet core. In the case where the pharmaceutical product is a 200 mg ribociclib tablet, the tablet core may comprise or consist of about 254 mg of ribociclib succinate, about 15 mg magnesium stearate, about 67 mg microcrystalline cellulose, about 42 mg crospovidone, about 48 mg hydroxypropyl cellulose and about 3 mg silica. Preferably, the tablet core may comprise or consist of about 254.40 mg of ribociclib succinate, about 14.82 mg magnesium stearate, about 67.44 mg microcrystalline cellulose, about 42.04 mg crospovidone, about 48.12 mg hydroxypropyl cellulose and about 3.18 mg silica. The total tablet core weight may be from about 94% to about 99%, preferably from about 95% to about 98%, preferably from about 96% to about 97%, preferably from about 96.05% to about 96.25%, preferably about 96.15% by weight of the total tablet weight. In the case where the tablet is a 200 mg ribociclib tablet, the total coated tablet weight may be about 447.20 mg and the total tablet core weight may be from about 425 mg to about 435 mg, preferably about 430.00 mg. In the case where the pharmaceutical product is a 200 mg ribociclib tablet, the tablet core may comprise or consist of the following: Ingredient Amount (mg) per 200 Function mg ribociclib tablet Ribociclib succinate 254.40 Drug substance Microcrystalline cellulose 67.44 Diluent Hydroxypropyl cellulose 48.12 Binder Crospovidone 42.04 Disintegrant Magnesium stearate 14.82 Lubricant PAT059729-WO-PCT03 51 Silica 3.18 Glidant In the case where the pharmaceutical product is a tablet, the tablet may comprise a film coating. The film coating may be a moisture barrier film coating. The film coating may be an aqueous moisture barrier (“amb”) film coating. Suitable amb coatings are known in the art, such as the Opadry® amb and Opadry® amb II film coatings which are commercially available through Colorcon, Inc. Opadry® amb film coatings are preferred. The film coating (such as the preferred amb film coating) may comprise iron oxide black (E172), iron oxide red (E172), soya lecithin (E322), polyvinyl alcohol (partially hydrolysed), talc, titanium dioxide (E171), and / or xanthan gum. The film coating may comprise or consist of about 0.5 wt% iron oxide black (E172), about 0.3 wt% iron oxide red (E172), about 2.0 wt% soya lecithin (E322), about 45.5 wt% polyvinyl alcohol (partially hydrolysed), about 20.0 wt% talc, about 31.3 wt% titanium dioxide (E171), and about 0.5 wt% xanthan gum, wherein the wt% are each defined relative to the weight of the film coating. Preferably, the film coating comprises or consists of about 0.47 wt% iron oxide black (E172), about 0.27 wt% iron oxide red (E172), about 2.00 wt% soya lecithin (E322), about 45.51 wt% polyvinyl alcohol (partially hydrolysed), about 20.00 wt% talc, about 31.26 wt% titanium dioxide (E171), and about 0.48 wt% xanthan gum, wherein the wt% are each defined relative to the weight of the film coating. In the case where the pharmaceutical product is a 200 mg ribociclib tablet, the film coating may comprise or consist of about 0.1 mg iron oxide black (E172), about 0.05 mg iron oxide red (E172), about 0.3 mg soya lecithin (E322), about 7.8 mg polyvinyl alcohol (partially hydrolysed), about 3.4 mg talc, about 5.4 mg titanium dioxide (E171), and about 0.1 mg xanthan gum. Preferably, the film coating may comprise or consist of about 0.08 mg iron oxide black (E172), about 0.05 mg iron oxide red (E172), about 0.34 mg soya lecithin (E322), about 7.83 mg polyvinyl alcohol (partially hydrolysed), about 3.44 mg talc, about 5.38 mg titanium dioxide (E171), and about 0.08 mg xanthan gum. The total film coating weight may be from about 1% to about 6%, preferably from about 2% to about 5%, more preferably from about 3% to about 4%, even more preferably from about 3.75% to about 3.95%, and most preferably about 3.84% by weight of the total tablet weight. In the case where the tablet is a 200 mg ribociclib tablet, the total coated tablet weight may be about 447.20 mg and the total coating weight may be from about 15 mg to about 20 mg, preferably about 17.20 mg. In the case where the pharmaceutical product is a 200 mg ribociclib tablet, the film coating may comprise or consist of the following premix ingredients: Ingredient Quantity (mg) per Function 200 mg ribociclib tablet Basic coating premix white PAT059729-WO-PCT03 52 Polyvinyl alcohol (partially hydrolysed) 7.649 Film-forming agent Titanium dioxide (E171) 5.377 Opacifier Talc 3.361 Anti-tacking agent Lecithin (soya) (E322) 0.336 Emulsifying agent Xanthan gum 0.081 Film-forming agent Basic coating premix black Polyvinyl alcohol (partially hydrolysed) 0.113 Film-forming agent Iron oxide black (E172) / ferrosoferric 0.080 Colorant oxide Talc 0.050 Anti-tacking agent Lecithin (soya) (E322) 0.005 Emulsifying agent Xanthan gum 0.001 Film-forming agent Basic coating premix red Polyvinyl alcohol (partially hydrolysed) 0.066 Film-forming agent Iron oxide red (E172) 0.047 Colorant Talc 0.029 Anti-tacking agent Lecithin (soya) (E322) 0.003 Emulsifying agent Xanthan gum 0.001 Film-forming agent The one or more pharmaceutically acceptable excipients may be or may comprise magnesium stearate. The content of nitrites in the magnesium stearate may be no more than about 7 ppm, optionally no more than about 5 ppm, no more than about 4 ppm, no more than about 3.5 ppm. The one or more pharmaceutically acceptable excipients may be or may comprise microcrystalline cellulose. The content of nitrites in the microcrystalline cellulose may be no more than about 500 ppb, no more than about 400 ppb, no more than about 300 ppb, no more than about 200 ppb, no more than about 100 ppb, less than about 100 ppb, no more than about 90 ppb, no more than about 80 ppb, no more than about 70 ppb, no more than about 60 ppb, no more than about 50 ppb, no more than about 40 ppb, no more than about 30 ppb, no more than about 20 ppb, or no more than about 10 ppb. Preferably, the content of nitrites in the microcrystalline cellulose may be no more than about 100 ppb or less than about 100 ppb. PAT059729-WO-PCT03 53 Suitable microcrystalline cellulose excipients are known to those skilled in the art and include types MCC PH102 and MCC PH105. The microcrystalline cellulose may be MCC PH102. The microcrystalline cellulose may have a bulk density of about 0.28 to about 0.33 g / mL. The one or more pharmaceutically acceptable excipients may be or may comprise cross-linked polyvinylpyrrolidone (also known as crospovidone). The content of nitrites in the crospovidone is preferably no more than or less than about 100 ppb, optionally no more than about 90 ppb, no more than about 80 ppb, no more than about 70 ppb, no more than about 60 ppb, no more than about 50 ppb, no more than about 40 ppb, no more than about 30 ppb, no more than about 20 ppb, or no more than about 10 ppb. Suitable cross-linked polyvinylpyrrolidone (also known as crospovidone) excipients are known to those skilled in the art. The cross-linked polyvinylpyrrolidone may be a Type A cross-linked polyvinylpyrrolidone. The one or more pharmaceutically acceptable excipients may be or may comprise hydroxypropyl cellulose. The content of nitrites in the hydroxypropyl cellulose may be no more than about 500 ppb, no more than about 400 ppb, no more than about 300 ppb, no more than about 200 ppb, no more than about 100 ppb, no more than about 90 ppb, no more than about 80 ppb, no more than about 70 ppb, no more than about 60 ppb, no more than about 50 ppb, no more than about 40 ppb, no more than about 30 ppb, no more than about 20 ppb, or no more than about 10 ppb. Preferably, the content of nitrites in the hydroxypropyl cellulose may be no more than about 100 ppb. Suitable hydroxypropyl cellulose excipients are known to those skilled in the art. The hydroxypropyl cellulose may be a low substituted hydroxypropyl cellulose. The one or more pharmaceutically acceptable excipients may be or may comprise silica. The content of nitrites in the silica may be no more than about 500 ppb, no more than about 400 ppb, no more than about 300 ppb, no more than about 200 ppb, or no more than about 100 ppb. As disclosed elsewhere herein, the amount of nitrites in a composition, e.g., the amount of nitrites in a pharmaceutically acceptable excipient, may be determined using the Griess test. Thus, the invention provides a method of preparing a composition comprising (i) ribociclib or a pharmaceutically acceptable salt thereof and (ii) one or more pharmaceutically acceptable excipients, wherein the method comprises the use of the Griess test to determine the amount of nitrites in one, a plurality, or each of the one or more excipients, optionally wherein the one or more excipients in which the amount of nitrites is determined is selected from the group consisting of magnesium stearate, microcrystalline cellulose, crospovidone, hydroxypropyl cellulose and silica. In some embodiments, the one or more excipients in which the amount of nitrites is determined is or comprises crospovidone. Additionally, or alternatively, the one or more excipients in which the amount of nitrites is determined is or comprises microcrystalline cellulose. PAT059729-WO-PCT03 It will be understood that the preferred pharmaceutical compositions discussed hereinabove (such as the preferred tablet core and / or the preferred tablet coating compositions) may be used in or as, or be applicable to, each of the compositions, embodiments, clauses, claims and statements of invention that are described elsewhere herein. The ribociclib or pharmaceutically acceptable salt thereof that is used in the methods of preparing a pharmaceutical composition may be prepared by the methods of preparing ribociclib or a pharmaceutically acceptable salt thereof that are described elsewhere herein. The invention further provides methods of preparing a pharmaceutical composition comprising (i) ribociclib or a pharmaceutically acceptable salt thereof and (ii) one or more additives, wherein the pharmaceutical composition is substantially free of nitrosamines, particularly N-nitroso-ribociclib in free or salt form. The one or more additives prevent, retard or reduce the formation of nitrosamines, particularly N-nitroso-ribociclib in free or salt form, during the method of preparation of the pharmaceutical composition and / or during the subsequent storage of the composition. For example, the one or more additives is selected from the group consisting of pH adjusters, antioxidants, radical scavenging agents, and peroxide-quenching agents. The method of preparing a pharmaceutical composition comprising ribociclib or a pharmaceutically acceptable salt thereof, and one or more additives, may comprise a step of mixing ribociclib or said pharmaceutically acceptable salt thereof with the one or more additives. Accordingly, one aspect of the present invention provides a method of preparing a pharmaceutical composition comprising (i) ribociclib or a pharmaceutically acceptable salt thereof and (ii) one or more additives, wherein the method comprises mixing the ribociclib or pharmaceutically acceptable salt thereof with the one or more additives, wherein the one or more additives prevent, retard, or reduce the formation of N-nitroso-ribociclib in free or salt form during storage of the composition, optionally wherein the one or more additives are each selected from the group consisting of pH adjusters, antioxidants, radical scavenging agents, and peroxide-quenching agents. Testing of the Drug Substance / Drug Product The invention further provides methods of testing the ribociclib or pharmaceutically acceptable salt thereof, as well as methods of testing the pharmaceutical compositions comprising (i) ribociclib or a pharmaceutically acceptable salt thereof and (ii) one or more pharmaceutically acceptable excipients, for the presence and / or amount of nitrosamines, in particular N-nitroso-ribociclib in free or salt form. Thus, an aspect of the invention relates to a method of evaluating a composition comprising or consisting of ribociclib or a pharmaceutically acceptable salt thereof, the method comprising testing the composition for the presence and / or amount of nitrosamines, in particular N-nitroso-ribociclib in free or salt form. The method may be used to validate a process for the production of a composition comprising or consisting of ribociclib or a pharmaceutically acceptable salt thereof. Thus, an aspect of the invention relates to a method PAT059729-WO-PCT03 55 of validating a process for the production of a composition comprising or consisting of ribociclib or a pharmaceutically acceptable salt thereof, the method comprising testing the composition produced by said process for the presence and / or amount of nitrosamines, in particular N-nitroso-ribociclib in free or salt form. Another aspect of the invention relates to a method of obtaining regulatory approval for a pharmaceutical composition which comprises or consists of ribociclib or a pharmaceutically acceptable salt thereof, wherein the method comprises (i) testing the composition for the presence and / or amount of nitrosamines, in particular N-nitroso-ribociclib in free or salt form, and (ii) submitting the results of said testing to a regulatory authority. Suitable regulatory authorities to which the results may be submitted are described elsewhere herein, e.g., the FDA, the EMA, the MHRA, Swissmedic, or the PMDA. In some aspects of the methods of the invention, a batch of the composition is tested to determine the presence and / or amount of nitrosamines in said batch, in particular the presence and / or total amount of N-nitroso- ribociclib in free or salt form. In particular, a sample of the batch is tested. The batch testing may be used to determine whether to prepare a pharmaceutical product from said batch. For example, a pharmaceutical product may be prepared from the batch only if the batch is determined to have a total amount of nitrosamines of no more than about 5 ppm, for example no more than about 4 ppm, no more than about 3 ppm, no more than about 2 ppm, no more than about 1 ppm, no more than about 0.9 ppm, no more than about 0.8 ppm, no more than about 0.7 ppm, no more than about 0.6 ppm, no more than about 0.5 ppm, no more than about 0.4 ppm, no more than about 0.3 ppm, no more than about 0.25 ppm, no more than about 0.2 ppm, no more than about 0.15 ppm, or no more than about 0.1 ppm. Preferably, the pharmaceutical product may be prepared from the batch only if the batch is determined to have a total amount of nitrosamines of no more than about 1 ppm. Thus, an aspect of the invention provides a process for preparing a pharmaceutical product comprising a composition that comprises: (i) ribociclib or a pharmaceutically acceptable salt thereof; and (ii) one or more pharmaceutically acceptable excipients, the process comprising: a. obtaining a batch of ribociclib or of a pharmaceutically acceptable salt thereof; b. determining the total amount of nitrosamines in said batch, in particular by testing a sample of the batch; and c. preparing the pharmaceutical product from the batch only if the batch is determined to have a total amount of nitrosamines of no more than about 1 ppm. In some aspects, the pharmaceutical product is prepared from the batch only if the batch is determined to have a total amount of nitrosamines of no more than about 0.9 ppm, no more than about 0.8 ppm, no more than about 0.7 ppm, no more than about 0.6 ppm, no more than about 0.5 ppm, no more than about 0.4 ppm, no more than about 0.3 ppm, no more than about 0.2 ppm, no more than about 0.1 ppm, no more than about 0.05 ppm, or no more than about 0.025 ppm. In a preferred aspect, the pharmaceutical product is prepared from the batch only if the batch is determined to have a total PAT059729-WO-PCT03 56 amount of nitrosamines of no more than about 0.7 ppm, for example no more than about 0.6 ppm or no more than about 0.4 ppm. In some aspects, a pharmaceutical product may be prepared from the batch only if the batch is determined to have a total amount of nitrosamines (such as N-nitroso-ribociclib in free or salt form) which would result in an amount of said nitrosamines (such as N-nitroso-ribociclib in free or salt form) that corresponds to an amount of no more than 400 ng / day of nitrosamine free base (such as no more than 400 ng / day of N-nitroso-ribociclib free base) being administered to the patient when the composition is administered according to an approved dosage regimen of the ribociclib or pharmaceutically acceptable salt thereof. Thus, an aspect of the invention provides a process for preparing a pharmaceutical product comprising a composition that comprises: (i) ribociclib or a pharmaceutically acceptable salt thereof; and (ii) one or more pharmaceutically acceptable excipients, the process comprising: a. obtaining a batch of ribociclib or of a pharmaceutically acceptable salt thereof; b. determining the total amount of nitrosamines (such as N-nitroso-ribociclib in free or salt form) in said batch, in particular by testing a sample of the batch; and c. preparing the pharmaceutical product from the batch only if the batch is determined to have a total amount of nitrosamines (such as N-nitroso-ribociclib in free or salt form) which would result in an amount of said nitrosamines (such as N-nitroso-ribociclib in free or salt form) that corresponds to an amount of no more than 400 ng / day of nitrosamine free base (such as no more than 400 ng / day of N-nitroso-ribociclib free base) being administered to the patient when the composition is administered according to an approved dosage regimen of the ribociclib or pharmaceutically acceptable salt thereof. In some aspects, a batch of the composition is tested to determine the total amount of N-nitroso-ribociclib in free or salt form in said batch. In particular, a sample of the batch is tested. This batch testing may be used to determine whether to prepare a pharmaceutical product from said batch. For example, a pharmaceutical product may be prepared from the batch only if the batch is determined to have a total amount of N-nitroso- ribociclib in free or salt form of no more than about 5 ppm, relative to the total amount of ribociclib in free or salt form, for example no more than about 4 ppm, no more than about 3 ppm, no more than about 2 ppm, or no more than about 1 ppm, relative to the total amount of ribociclib in free or salt form. Preferably, a pharmaceutical product may be prepared from the batch only if the batch is determined to have a total amount of N-nitroso-ribociclib in free or salt form of no more than about 1 ppm, relative to the total amount of ribociclib in free or salt form. Thus, an aspect of the invention provides a process for preparing a pharmaceutical product comprising a composition that comprises: (i) ribociclib or a pharmaceutically acceptable salt thereof; and (ii) one or more pharmaceutically acceptable excipients, the process comprising: a. obtaining a batch of ribociclib or of a pharmaceutically acceptable salt thereof; b. determining the total amount of N-nitroso-ribociclib in free or salt form in said batch, in particular by testing a sample of the batch; and PAT059729-WO-PCT03 57 c. preparing the pharmaceutical product from the batch only if the batch is determined to have a total amount of N-nitroso-ribociclib in free or salt form of no more than about 1 ppm, relative to the total amount of ribociclib in free or salt form. In some aspects, the pharmaceutical product is prepared from the batch only if the batch is determined to have a total amount of N-nitroso-ribociclib in free or salt form of no more than about 0.9 ppm, no more than about 0.8 ppm, no more than about 0.7 ppm, no more than about 0.6 ppm, no more than about 0.5 ppm, no more than about 0.4 ppm, no more than about 0.3 ppm, no more than about 0.2 ppm, no more than about 0.1 ppm, no more than about 0.05 ppm, or no more than about 0.025 ppm, relative to the total amount of ribociclib in free or salt form. In a preferred aspect, the pharmaceutical product is prepared from the batch only if the batch is determined to have a total amount of N-nitroso-ribociclib in free or salt form of no more than about 0.7 ppm, for example no more than about 0.6 ppm or no more than about 0.4 ppm. In some aspects, a pharmaceutical product may be prepared from the batch only if the batch is determined to have a total amount of N-nitroso-ribociclib in free or salt form which would result in an amount of said N-nitroso- ribociclib in free or salt form that corresponds to an amount of no more than 400 ng / day of said N-nitroso- ribociclib free base being administered to the patient when the composition is administered according to an approved dosage regimen of the ribociclib or pharmaceutically acceptable salt thereof. Thus, an aspect of the invention provides a process for preparing a pharmaceutical product comprising a composition that comprises: (i) ribociclib or a pharmaceutically acceptable salt thereof; and (ii) one or more pharmaceutically acceptable excipients, the process comprising: a. obtaining a batch of ribociclib or of a pharmaceutically acceptable salt thereof; b. determining the total amount of N-nitroso-ribociclib in free or salt form in said batch, in particular by testing a sample of the batch; and c. preparing the pharmaceutical product from the batch only if the batch is determined to have a total amount of N-nitroso-ribociclib in free or salt form which would result in an amount of said N-nitroso-ribociclib in free or salt form that corresponds to an amount of no more than 400 ng / day of N-nitroso-ribociclib free base being administered to the patient when the composition is administered according to an approved dosage regimen of the ribociclib or pharmaceutically acceptable salt thereof. In some aspects, a batch of the composition is tested to determine the amount of total nitrosamines, including both N-nitroso-ribociclib in free or salt form and other nitrosamines, in said batch. In particular, a sample of the batch is tested. This batch testing may be used to determine whether to prepare a pharmaceutical product from said batch. For example, a pharmaceutical product may be prepared from the batch only if the batch is determined to have an amount of total nitrosamines, including N-nitroso-ribociclib in free or salt form and other nitrosamines, of no more than about 5 ppm, for example no more than about 4 ppm, no more than about 3 ppm, no more than about 2 ppm, or no more than about 1 ppm. Preferably, a pharmaceutical product may be prepared from the batch only if the batch is determined to have an amount of total nitrosamines, including both N-nitroso-ribociclib in free or salt form and other nitrosamines, of no more than about 1 ppm. Thus, an aspect of the invention provides a process for preparing a pharmaceutical product comprising a composition that PAT059729-WO-PCT03 58 comprises: (i) ribociclib or a pharmaceutically acceptable salt thereof; and (ii) one or more pharmaceutically acceptable excipients, the process comprising: a. obtaining a batch of ribociclib or of a pharmaceutically acceptable salt thereof; b. determining the amount of total nitrosamines, including both N-nitroso-ribociclib in free or salt form and other nitrosamines, in said batch, in particular by testing a sample of the batch; and c. preparing the pharmaceutical product from the batch only if the batch is determined to have an amount of total nitrosamines, including both N-nitroso-ribociclib in free or salt form and other nitrosamines, of no more than about 1 ppm. In some aspects, the pharmaceutical product is prepared from the batch only if the batch is determined to have an amount of total nitrosamines, including both N-nitroso-ribociclib in free or salt form and other nitrosamines, of no more than about 0.9 ppm, no more than about 0.8 ppm, no more than about 0.7 ppm, no more than about 0.6 ppm, no more than about 0.5 ppm, no more than about 0.4 ppm, no more than about 0.3 ppm, no more than about 0.2 ppm, no more than about 0.1 ppm, no more than about 0.05 ppm, or no more than about 0.025 ppm. In some aspects, the pharmaceutical product is prepared from the batch only if the batch is determined to have an amount of total nitrosamines, including both N-nitroso-ribociclib in free or salt form and other nitrosamines, of no more than about 0.7 ppm, for example no more than about 0.6 ppm or no more than about 0.4 ppm. In some aspects, a pharmaceutical product may be prepared from the batch only if the batch is determined to have an amount of total nitrosamines, including both N-nitroso-ribociclib in free or salt form and other nitrosamines, which would result in an amount of said total nitrosamines that corresponds to an amount of no more than 400 ng / day of nitrosamine free base being administered to the patient when the composition is administered according to an approved dosage regimen of ribociclib or pharmaceutically acceptable salt thereof. Thus, an aspect of the invention provides a process for preparing a pharmaceutical product comprising a composition that comprises: (i) ribociclib or a pharmaceutically acceptable salt thereof; and (ii) one or more pharmaceutically acceptable excipients, the process comprising: a. obtaining a batch of ribociclib or of a pharmaceutically acceptable salt thereof; b. determining the amount of total nitrosamines, including both N-nitroso-ribociclib in free or salt form and other nitrosamines, in said batch, in particular by testing a sample of the batch; and c. preparing the pharmaceutical product from the batch only if the batch is determined to have an amount of total nitrosamines, including both N-nitroso-ribociclib in free or salt form and other nitrosamines, which would result in an amount of said total nitrosamines that corresponds to an amount of no more than 400 ng / day of nitrosamine free base being administered to the patient when the composition is administered according to an approved dosage regimen of ribociclib or pharmaceutically acceptable salt thereof. In each of the above aspects of the invention, the batch of ribociclib or of a pharmaceutically acceptable salt thereof that is obtained in step a. of the process may be a batch of the ribociclib drug substance (i.e., a batch of the ribociclib free base or a batch of a pharmaceutically acceptable salt of ribociclib), or it may be a batch PAT059729-WO-PCT03 59 of a ribociclib drug product, (i.e., a batch in which the ribociclib or pharmaceutically acceptable salt thereof is combined with one or more pharmaceutically acceptable excipients). In some aspects, stability testing may be performed using a sample of a batch of the composition. Following this stability testing, the sample of the batch may be tested for the total amount of nitrosamines (such as N- nitroso-ribociclib in free or salt form). This testing of the sample of the batch may be used to determine whether the batch is suitable for distribution and / or administration to a patient. For example, the batch may be determined to be suitable for distribution only if the sample of the batch after stability testing is determined to have a total amount of nitrosamines (such as N-nitroso-ribociclib in free or salt form) of no more than about 5 ppm, for example no more than about 4 ppm, no more than about 3 ppm, no more than about 2 ppm, or no more than about 1 ppm. Preferably, the batch may be determined to be suitable for distribution only if the sample of the batch after stability testing is determined to have a total amount of nitrosamines (such as N- nitroso-ribociclib in free or salt form) of no more than about 1 ppm. Thus, an aspect of the invention provides a process of distributing a validated batch of a pharmaceutical product comprising a composition that comprises: (i) ribociclib or a pharmaceutically acceptable salt thereof; and (ii) one or more pharmaceutically acceptable excipients, the process comprising: a. producing a batch of the pharmaceutical product; b. performing stability testing with a sample of said batch; c. determining the total amount of nitrosamines (such as N-nitroso-ribociclib in free or salt form) in the sample of the batch after stability testing; and d. validating the batch for distribution only if the sample of the batch after stability testing is determined to have a total amount of nitrosamines (such as N-nitroso-ribociclib in free or salt form) of no more than about 1 ppm. In some aspects, the batch is validated for distribution only if the sample of the batch after stability testing is determined to have a total amount of nitrosamines (such as N-nitroso-ribociclib in free or salt form) of no more than about 0.9 ppm, no more than about 0.8 ppm, no more than about 0.7 ppm, no more than about 0.6 ppm, no more than about 0.5 ppm, no more than about 0.4 ppm, no more than about 0.3 ppm, no more than about 0.2 ppm, no more than about 0.1 ppm, no more than about 0.05 ppm, or no more than about 0.025 ppm. In a preferred aspect, the batch is validated for distribution only if the sample of the batch after stability testing is determined to have a total amount of nitrosamines (such as N-nitroso-ribociclib in free or salt form) of no more than about 0.7 ppm, for example no more than 0.6 ppm or no more than about 0.4 ppm. In some aspects, the batch may be determined to be suitable for distribution only if the sample of the batch after stability testing is determined to have a total amount of nitrosamines (such as N-nitroso-ribociclib in free or salt form) which would result in an amount of said nitrosamines (such as N-nitroso-ribociclib in free or salt form) that corresponds to an amount of no more than 400 ng / day of nitrosamine free base (such as no more than 400 ng / day of N-nitroso-ribociclib free base) being administered to the patient when the composition is administered according to an approved dosage regimen of ribociclib or pharmaceutically acceptable salt thereof. Thus, an aspect of the invention provides a process of distributing a validated batch of a PAT059729-WO-PCT03 60 pharmaceutical product comprising a composition that comprises: (i) ribociclib or a pharmaceutically acceptable salt thereof; and (ii) one or more pharmaceutically acceptable excipients, the process comprising: a. producing a batch of the pharmaceutical product; b. performing stability testing with a sample of said batch; c. determining the total amount of nitrosamines (such as N-nitroso-ribociclib in free or salt form) in the sample of the batch after stability testing; and d. validating the batch for distribution only if the sample of the batch after stability testing is determined to have a total amount of nitrosamines (such as N-nitroso-ribociclib in free or salt form) which would result in an amount of said nitrosamines (such as N-nitroso-ribociclib in free or salt form) that corresponds to an amount of no more than 400 ng / day of nitrosamine free base (such as no more than 400 ng / day of N-nitroso-ribociclib free base) being administered to the patient when the composition is administered according to an approved dosage regimen of ribociclib or pharmaceutically acceptable salt thereof. In some aspects, stability testing may be performed using a sample of a batch of the composition and the sample of the batch may be tested for the total amount of N-nitroso-ribociclib in free or salt form in said sample of the batch after stability testing. This testing of the sample of the batch may be used to determine whether the batch is suitable for distribution and / or administration to a patient. For example, the batch may be determined to be suitable for distribution only if the sample of the batch after stability testing is determined to have a total amount of N-nitroso-ribociclib in free or salt form of no more than about 5 ppm, relative to the total amount of ribociclib in free or salt form, for example no more than about 4 ppm, no more than about 3 ppm, no more than about 2 ppm, or no more than about 1 ppm, relative to the total amount of ribociclib in free or salt form. Preferably, the batch may be determined to be suitable for distribution only if the sample of the batch after stability testing is determined to have a total amount of N-nitroso-ribociclib in free or salt form of no more than about 1 ppm, relative to the total amount of ribociclib in free or salt form. Thus, an aspect of the invention provides a process of distributing a validated batch of a pharmaceutical product comprising a composition that comprises: (i) ribociclib or a pharmaceutically acceptable salt thereof; and (ii) one or more pharmaceutically acceptable excipients, the process comprising: a. producing a batch of the pharmaceutical product; b. performing stability testing with a sample of said batch; c. determining the total amount of N-nitroso-ribociclib in free or salt form in said sample of said batch after stability testing; and d. validating the batch for distribution only if the sample of the batch after stability testing is determined to have a total amount of N-nitroso-ribociclib in free or salt form of no more than about 1 ppm, relative to the total amount of ribociclib in free or salt form. In some aspects, the batch is validated for distribution only if the sample of the batch after stability testing is determined to have a total amount of N-nitroso-ribociclib in free or salt form of no more than about 0.9 ppm, no more than about 0.8 ppm, no more than about 0.7 ppm, no more than about 0.6 ppm, no more than about 0.5 ppm, no more than about 0.4 ppm, no more than about 0.3 ppm, no more than about 0.2 ppm, no more than about 0.1 ppm, no more than about 0.05 ppm, or no more than PAT059729-WO-PCT03 61 about 0.025 ppm, relative to the total amount of ribociclib in free or salt form. In a preferred aspect, the batch is validated for distribution only if the sample of the batch after stability testing is determined to have a total amount of N-nitroso-ribociclib in free or salt form of no more than about 0.7 ppm, for example no more than 0.6 ppm or no more than about 0.4 ppm. In some aspects, the batch may be determined to be suitable for distribution only if the sample of the batch after stability testing is determined to have a total amount of N-nitroso-ribociclib in free or salt form which would result in an amount of said N-nitroso-ribociclib in free or salt form that corresponds to an amount of no more than 400 ng / day of N-nitroso-ribociclib free base being administered to the patient when the composition is administered according to an approved dosage regimen of ribociclib or pharmaceutically acceptable salt thereof. Thus, an aspect of the invention provides a process of distributing a validated batch of a pharmaceutical product comprising a composition that comprises: (i) ribociclib or a pharmaceutically acceptable salt thereof; and (ii) one or more pharmaceutically acceptable excipients, the process comprising: a. producing a batch of the pharmaceutical product; b. performing stability testing with a sample of said batch; c. determining the total amount of N-nitroso-ribociclib in free or salt form in the sample of the batch after stability testing; and d. validating the batch for distribution only if the sample of the batch after stability testing is determined to have a total amount of N-nitroso-ribociclib in free or salt form which would result in an amount of said N- nitroso-ribociclib in free or salt form that corresponds to an amount of no more than 400 ng / day of N-nitroso- ribociclib free base being administered to the patient when the composition is administered according to an approved dosage regimen of ribociclib or pharmaceutically acceptable salt thereof. In some aspects, stability testing may be performed using a sample of a batch of the composition and the sample of the batch may be tested for the amount of total nitrosamines, including both N-nitroso-ribociclib in free or salt form and other nitrosamines, in said batch after stability testing. This testing of the sample of the batch may be used to determine whether the batch is suitable for distribution and / or administration to a patient. For example, the batch may be determined to be suitable for distribution only if the sample of the batch after stability testing is determined to have an amount of total nitrosamines, including both N-nitroso-ribociclib in free or salt form and other nitrosamines, of no more than about 5 ppm, for example no more than about 4 ppm, no more than about 3 ppm, no more than about 2 ppm, or no more than about 1 ppm. Preferably, the batch may be determined to be suitable for distribution only if the sample of the batch after stability testing is determined to have an amount of total nitrosamines, including both N-nitroso-ribociclib in free or salt form and other nitrosamines, of no more than about 1 ppm. Thus, an aspect of the invention provides a process of distributing a validated batch of a pharmaceutical product comprising a composition that comprises: (i) ribociclib or a pharmaceutically acceptable salt thereof; and (ii) one or more pharmaceutically acceptable excipients, the process comprising: a. producing a batch of the pharmaceutical product; PAT059729-WO-PCT03 62 b. performing stability testing with a sample of said batch; c. determining the amount of total nitrosamines, including both N-nitroso-ribociclib in free or salt form and other nitrosamines, in said batch after stability testing; and d. validating the batch for distribution only if the sample of the batch after stability testing is determined to have an amount of total nitrosamines, including both N-nitroso-ribociclib in free or salt form and other nitrosamines, of no more than about 1 ppm. In some aspects, the batch is validated for distribution only if the sample of the batch after stability testing is determined to have an amount of total nitrosamines, including both N-nitroso-ribociclib in free or salt form and other nitrosamines, of no more than about 0.9 ppm, no more than about 0.8 ppm, no more than about 0.7 ppm, no more than about 0.6 ppm, no more than about 0.5 ppm, no more than about 0.4 ppm, no more than about 0.3 ppm, no more than about 0.2 ppm, no more than about 0.1 ppm, no more than about 0.05 ppm, or no more than about 0.025 ppm. In a preferred aspect, the batch is validated for distribution only if the sample of the batch after stability testing is determined to have an amount of total nitrosamines, including both N-nitroso-ribociclib in free or salt form and other nitrosamines, of no more than about 0.7 ppm, for example no more than 0.6 ppm or no more than about 0.4 ppm. In some aspects, the batch may be determined to be suitable for distribution only if the sample of the batch after stability testing is determined to have an amount of total nitrosamines, including both N-nitroso-ribociclib in free or salt form and other nitrosamines, which would result in an amount of said total nitrosamines which corresponds to an amount of no more than 400 ng / day of nitrosamine free base being administered to the patient when the composition is administered according to an approved dosage regimen of ribociclib or pharmaceutically acceptable salt thereof. Thus, an aspect of the invention provides a process of distributing a validated batch of a pharmaceutical product comprising a composition that comprises: (i) ribociclib or a pharmaceutically acceptable salt thereof; and (ii) one or more pharmaceutically acceptable excipients, the process comprising: a. producing a batch of the pharmaceutical product; b. performing stability testing with a sample of said batch; c. determining the amount of total nitrosamines, including both N-nitroso-ribociclib in free or salt form and other nitrosamines, in the sample of the batch after stability testing; and d. validating the batch for distribution only if the sample of the batch after stability testing is determined to have an amount of total nitrosamines, including both N-nitroso-ribociclib in free or salt form and other nitrosamines, which would result in an amount of said total nitrosamines which corresponds to an amount of no more than 400 ng / day of nitrosamine free base being administered to the patient when the composition is administered according to an approved dosage regimen of ribociclib or pharmaceutically acceptable salt thereof. In any of these methods, the step of testing for the presence and / or amount of nitrosamines may be performed using the Griess test. Likewise, the step of determining the presence and / or total amount of N-nitroso-ribociclib in free or salt form may be performed using the Griess test. PAT059729-WO-PCT03 Alternatively, in any of these methods, the step of testing for the presence and / or amount of nitrosamines may be performed using high performance liquid chromatography (HPLC)- and / or gas chromatography (GC)-mass spectroscopy. Likewise, the step of determining the total amount of N-nitroso-ribociclib in free or salt form may be performed using high performance liquid chromatography (HPLC)- and / or gas chromatography (GC)-mass spectroscopy. For example, the HPLC-MS method performed may be the method provided in Example 14. The invention also provides for the use of N-nitroso-ribociclib or a salt thereof as a reference standard to detect an impurity in a composition comprising ribociclib or a pharmaceutically acceptable salt thereof. The composition may comprise ribociclib or a pharmaceutically acceptable salt thereof and one or more pharmaceutically acceptable excipients. The impurity may be N-nitroso-ribociclib in free or salt form. The detection of the impurity may be performed using the Griess test. Alternatively, the detection of the impurity may be performed using high performance liquid chromatography (HPLC)- and / or gas chromatography (GC)- mass spectroscopy. The invention further provides a process for preparing a pharmaceutical product comprising a composition that comprises: (i) ribociclib or a pharmaceutically acceptable salt thereof; and (ii) one or more pharmaceutically acceptable excipients, the process comprising: a. preparing a first batch of a composition comprising or consisting of ribociclib or a pharmaceutically acceptable salt thereof; b. determining the total amount of N-nitroso-ribociclib in free or salt form in a sample of said first batch; c. discarding the first batch if the first batch is determined to have a total amount of N-nitroso-ribociclib in free or salt form of more than 1 ppm, relative to the total amount of ribociclib in free or salt form; and d. preparing a second batch of a composition comprising or consisting of ribociclib or a pharmaceutically acceptable salt thereof; wherein the reagents and / or conditions that are used in step d are adjusted relative to the reagents and / or conditions that are used in step a so as to prevent, retard or reduce the formation of N-nitroso-ribociclib in free or salt form. The first batch may be discarded if the first batch is determined to have a total amount of N-nitroso-ribociclib in free or salt form of more than 0.7 ppm, relative to the total amount of ribociclib in free or salt form. More preferably, the first batch is discarded if the first batch is determined to have a total amount of N-nitroso- ribociclib in free or salt form of more than 0.6 ppm, relative to the total amount of ribociclib in free or salt form. As a person of ordinary skill in the art will readily appreciate, “discarding the first batch” includes, for example, rejecting the first batch for further use, throwing away the first batch, destroying the first batch, repurposing the first batch, and / or recycling one or more components from the first batch. PAT059729-WO-PCT03 64 The step of determining the total amount of N-nitroso-ribociclib in free or salt form may be performed by a method which includes the Griess test and / or by high performance liquid chromatography (HPLC)-mass spectroscopy and / or gas chromatography (GC)-mass spectroscopy. The reagents and / or conditions that are adjusted in the process may include any one or any combination of the following: the ribociclib or pharmaceutically acceptable salt thereof, optionally wherein the pharmaceutically acceptable salt is ribociclib succinate; the one or more pharmaceutically acceptable excipients, optionally wherein the one or more pharmaceutically acceptable excipients are selected from the group consisting of magnesium stearate, microcrystalline cellulose, crospovidone, hydroxypropyl cellulose, and silica; and one or more solvents that are used in preparing the composition, optionally wherein the one or more solvents is or comprises isopropanol. The invention further provides a corresponding process in which the amount of total nitrosamines, including both N-nitroso-ribociclib in free or salt form and other nitrosamines, is determined in step b, and in step c, the first batch is discarded if it is determined to have an amount of total nitrosamines, including both N-nitroso- ribociclib in free or salt form and other nitrosamines, which exceeds the relevant threshold (e.g., 1 ppm, 0.7 ppm, or 0.6 ppm). In step d, the reagents and / or conditions are adjusted to prevent, retard or reduce the formation of total nitrosamines, or at least to prevent, retard or reduce the formation of N-nitroso-ribociclib in free or salt form. In a related aspect, the invention provides a process for preparing a pharmaceutical product comprising a composition that comprises: (i) ribociclib or a pharmaceutically acceptable salt thereof; and (ii) one or more pharmaceutically acceptable excipients, the process comprising: a. preparing a first batch of a composition comprising or consisting of ribociclib or a pharmaceutically acceptable salt thereof; b. determining the total amount of N-nitroso-ribociclib in free or salt form in a sample of said first batch; and c. adjusting the process (e.g., the reagents and / or conditions) in order to reduce the total amount of N- nitroso-ribociclib in free or salt form in the composition relative to the total amount of N-nitroso-ribociclib in free or salt form as determined for the first batch. The process may be adjusted such that or until the total amount of N-nitroso-ribociclib in free or salt form satisfies a requirement as specified herein for the total amount of N-nitroso-ribociclib in free or salt form, e.g., a requirement as to the maximum ppm relative to the total amount of ribociclib in free or salt form (such as the requirement that the total amount of N-nitroso-ribociclib in free or salt form is no more than 1 ppm, preferably PAT059729-WO-PCT03 65 no more than 0.7 ppm, and more preferably no more than 0.6 ppm, relative to the total amount of ribociclib in free or salt form). The invention further provides a corresponding process in which it is the amount of total nitrosamines, including both N-nitroso-ribociclib in free or salt form and other nitrosamines, that is determined in step b, and in which, in step c, the process is adjusted in order to reduce the amount of total nitrosamines, including both N-nitroso- ribociclib in free or salt form and other nitrosamines, in the composition. The process may be adjusted such that or until the amount of total nitrosamines, including both N-nitroso-ribociclib in free or salt form and other nitrosamines, satisfies a requirement as specified herein for the amount of total nitrosamines that is permitted in a composition (e.g., a requirement that there should be no more than 1 ppm, preferably no more than 0.7 ppm, and more preferably no more than 0.6 ppm, relative to the total amount of ribociclib in free or salt form). Optionally, the process of this related aspect of the invention may comprise a further step d of preparing a second batch of a composition comprising or consisting of ribociclib or a pharmaceutically acceptable salt thereof using the process as adjusted in step c. Adjusting the reagents in any process of the invention may be performed as described herein, e.g., by reducing the amount of nitrites in the potassium carbonate that may be used in any step in which intermediate B9 is deprotected to provide ribociclib B10 (such as by substituting a first batch or source of the potassium carbonate with a second batch or source of the potassium carbonate having a lower content of nitrites), by reducing the amount of nitrites in the organic or inorganic acid (such as succinic acid) that may be reacted with ribociclib free base in any step of forming a pharmaceutically acceptable salt of ribociclib (such as by substituting a first batch or source of the acid with a second batch or source of the acid having a lower content of nitrites and / or by passing the acid through an ion exchange resin as described elsewhere herein), by reducing the amount of nitrites in any pharmaceutically acceptable excipient or combination of pharmaceutically acceptable excipients that may be used in the process (such as by substituting a first batch or source of the excipient(s) with a second batch or source of the excipient(s) having a lower content of nitrites), by reducing the amount of nitrites in any of the solvents that may be used in the process (such as by substituting a first batch or source of the solvent with a second batch or source of the solvent having a lower content of nitrites, by distilling the solvent as described elsewhere herein, and / or by passing the solvent through an ion exchange resin as described elsewhere herein), and / or by reducing the exposure to oxygen of any of the solvents that may be used in the process (such as by substituting a first batch or source of a solvent with a second batch or source of the solvent having a lower content of dissolved oxygen or a lower content of oxygen in the headspace of its container and / or by sparging the solvent with an inert gas – examples of such gases being identified herein). Adjusting the reagents in any process of the invention for preparing a drug product may also be performed by substituting a first batch or source of ribociclib or a pharmaceutically acceptable salt thereof with a second batch or source of ribociclib or a pharmaceutically acceptable salt thereof having a lower content of N-nitroso- ribociclib and / or a lower content of total nitrosamines. PAT059729-WO-PCT03 Adjusting the process conditions in any process of the invention may also be performed as described elsewhere herein, e.g., by adding the solution of ribociclib free base last to the mixing vessel in any step of the process in which a solution of the free base is mixed with a solution of an acid in order to form a pharmaceutically acceptable salt of ribociclib, by filtering any solution of ribociclib and / or any solution of a pharmaceutically acceptable salt of ribociclib and / or any solution of an acid that is used to make a pharmaceutically acceptable salt of ribociclib through a filter which does not comprise a nitrocellulose membrane, by washing any crystalline form of ribociclib or any crystalline form of a pharmaceutically acceptable salt of ribociclib with a solvent that is substantially free of nitrites, by storing any composition of ribociclib or any composition of a pharmaceutically acceptable salt of ribociclib in the presence of a desiccant, by storing any composition of ribociclib or any composition of a pharmaceutically acceptable salt of ribociclib under an atmosphere in which the percentage of oxygen is less than 21% by volume, by storing any composition of ribociclib or any composition of a pharmaceutically acceptable salt of ribociclib under an atmosphere in which the humidity is no more than 2.5 g / kg (e.g., in which the relative humidity is no more than 15%), and / or by storing any composition of ribociclib or any composition of a pharmaceutically acceptable salt of ribociclib under refrigerated conditions. Manufacture of the Pharmaceutical Product The invention further provides methods of preparing a pharmaceutical product as described herein, and in particular a pharmaceutical product comprising a plurality of oral dosage forms as described herein. While the methods are described separately below, it will be readily apparent to a person of ordinary skill in the art that two or more of these methods may also be used in combination. Thus, the present invention also provides these combined methods of preparing a pharmaceutical product as described herein, e.g., a pharmaceutical product comprising a plurality of oral dosage forms as described herein. One such aspect of the invention provides a method of preparing a pharmaceutical product comprising a plurality of oral dosage forms, wherein each of the oral dosage forms is a tablet, and wherein said oral dosage forms comprise a composition comprising: (i) ribociclib or a pharmaceutically acceptable salt thereof; and (ii) one or more pharmaceutically acceptable excipients, wherein the method comprises: (a) providing the composition and (b) compressing the composition into tablets. Preferably, the method comprises a further step of (c) drying the tablets. The drying of the tablets is preferably carried out until the water activity value of the tablets is less than 0.2, for example wherein the water activity value of the tablets is no more than 0.18, no more than 0.16, no more than 0.14, no more than 0.12, less than 0.12, no more than 0.10, less than 0.10, no more than 0.08, less than 0.08, no more than 0.075, no more than 0.07, no more than 0.065, no more than 0.06, no more than 0.055, no more than 0.05, or no more than 0.045. More preferably, the drying of the tablets is carried out until the water activity PAT059729-WO-PCT03 67 value of the tablets is less than 0.08, more preferably until the water activity value of the tablets is no more than 0.06, most preferably no more than 0.05. Methods of measuring water activity are commonly known in the art and would be readily available to the skilled person. For example, the method used to measure the water activity may be USP <922> of the United States Pharmacopeia, e.g., as published in May 2021. Where the tablet is round, the tablet may be cut in half perpendicular to the diameter of the tablet, with the water activity measurement being performed on the said cut tablet. Optionally, the water activity measurement may be performed on a plurality of tablets (e.g., eight tablets, such as eight film-coated tablets). In some embodiments, the method further comprises a step of applying a coating to each of the tablets before the step of drying the tablets. The coating may be a film coating. Optionally the coating is a moisture barrier film coating, as described elsewhere herein.The step of drying the tablets may be conducted at a temperature of about 25 C to about 50 C, e.g., at atemperature of about 25 C to about 40 C, about 25 C to about 35 C, about 28 C to about 32 C, or about 30 C.Preferably, the step of drying the tablets is conducted at a temperature of about 28 C to about 32 C, and morepreferably at a temperature of about 30 C.The step of drying the tablets may be conducted for a time period of at least 44 hours, at least 48 hours, at least 52 hours, at least 56 hours, at least 60 hours, at least 64 hours, at least 68 hours, or at least 72 hours, preferably wherein the step of drying the tablets is conducted for a time period of at least 56 hours. The time period may a time period within the range of 44 hours to 72 hours, 48 hours to 68 hours, 52 hours to 64 hours, 56 hours to 64 hours, or 56 hours to 60 hours, preferably wherein the time period is at least 56 hours.The step of drying the tablets may be conducted at a temperature of about 25 C to about 50 C, preferably ata temperature of about 28 C to about 32 C, and more preferably at a temperature of about 30 C, for a timeperiod of at least 44 hours, at least 48 hours, at least 52 hours, at least 56 hours, at least 60 hours, at least 64 hours, at least 68 hours, or at least 72 hours, preferably wherein the step of drying the tablets is conducted for a time period of at least 56 hours. In one embodiment, the step of drying the tablets may be conducted at atemperature of about 28 C to about 32 C for a time period of at least 44 hours, and preferably at least 56hours. In another embodiment, the step of drying the tablets may be conducted at a temperature of about 30 Cfor a time period of at least 44 hours, and preferably at least 56 hours. The step of drying the tablets may be conducted by flowing an atmosphere over the tablets, wherein the humidity of the atmosphere is no more than 0.5 g / kg, preferably no more than 0.1 g / kg, and more preferably no more than 0.01 g / kg. In some embodiments, the relative humidity of the atmosphere is about 0 %. As will be appreciated by a person of ordinary skill in the art, the humidity and relative humidity of the atmosphere PAT059729-WO-PCT03 68 that is flowed over the tablets as described herein in the context of the step of drying the tablets preferably define the inlet air humidity and inlet relative air humidity, respectively. Any technique for drying the tablets by flowing such a low humidity atmosphere over the tablets may be used in the methods of the present invention. The selected technique and apparatus used therein should preferably allow the humidity, temperature and / or flow rate of the atmosphere to be controlled. One such technique involves fluid bed drying, in which case, a Huettlin fluid bed dryer (otherwise known as a Hüttlin device) may be used. Alternatively, a drying technique other than fluid bed drying is used, such as a technique in which the flow rate of the atmosphere is less than the flow rate that is typically used in fluid bed drying.The flow rate of the atmosphere may be less than 3000 m3 / h, e.g., less than 2500 m3 / h, less than 2000 m3 / h,less than 1500 m3 / h, less than 1000 m3 / h, or less than 500 m3 / h, preferably wherein the flow rate is less than 100 m3 / h. For example, the flow rate may be about 20 to about 100 m3 / h, about 20 to about 75 m3 / h, about 20 to about 50 m3 / h, about 25 to about 40 m3 / h, about 26 to about 35 m3 / h, or about 28 to about 30 m3 / h, preferably wherein the flow rate of the atmosphere is about 28 to about 30 m3 / h. The use of lower atmospheric flow rates means that the tablets are less exposed to any NOx species in the atmosphere. It is believed that this will result in a reduced formation of nitrosamines in the tablets, e.g., a reduced formation of N-nitroso-ribociclib in free or salt form in the tablets, during their subsequent storage. As will be appreciated by a person of ordinary skill in the art, if the drying technique and apparatus used in the drying technique comprises multiple drying vessels that are used in parallel, the flow rates described herein represent the normed flow rate (i.e., the flow rate per individual vessel). For example, if the drying apparatus used comprises four parallel drying vessels and the flow rate of the atmosphere is specified as 30 m3 / h, then the total flow rate would be 120 m3 / h, and this total flow rate would be distributed across the four vessels. Preferably, in the embodiment in which the step of drying the tablets is conducted by flowing an atmosphere over the tablets, the atmosphere is air. Prior to being flowed over the tablets, the air may be treated to reduce its content of NOx species, for example by subjecting the air to an NOx absorption pretreatment device such as a NOx scrubber, by subjecting the air to selective catalytic reduction, by subjecting the air to electron beam flue gas treatment, and / or by using scavengers to remove NOx from the air. Alternatively, the step of drying the tablets may be conducted by vacuum drying, such as by HSM vacuum drying. In some embodiments of the methods of the invention which comprise a step of drying the tablets, the total amount of nitrosamines in each of the tablets, or at least the total amount of N-nitroso-ribociclib in free or salt form in each of the tablets, is no more than 0.7 ppm, and preferably no more than 0.6 ppm, relative to the total amount of ribociclib in free or salt form, both before and after the step of drying the tablets. PAT059729-WO-PCT03 69 In these methods of the invention of preparing a pharmaceutical product comprising a plurality of tablets, the one or more pharmaceutically acceptable excipients which are present in the composition, including the amounts of those excipients, may be as described elsewhere herein. In particular, the one or more pharmaceutically acceptable excipients may be selected from the group consisting of magnesium stearate, microcrystalline cellulose, crospovidone, hydroxypropyl cellulose, and silica. The one or more pharmaceutically acceptable excipients may comprise each of magnesium stearate, microcrystalline cellulose, crospovidone, hydroxypropyl cellulose, and silica. The content of nitrites in the one or more excipients that are used in the preparation of the composition that is provided in step (a) and / or the content of nitrites in each of the tablets after the drying step (c) may be as described elsewhere herein. For example, the composition may comprise microcrystalline cellulose and crospovidone and (1) the content of nitrites in the microcrystalline cellulose may be no more than 100 ppb and / or (2) the content of nitrites in the crospovidone may be no more than 100 ppb. Additionally, or alternatively, the tablets after the drying step may have a total content of nitrites of no more than 5 ppm, no more than 4 ppm, no more than 3 ppm, no more than 2 ppm, no more than 1 ppm, or no more than 0.5 ppm, preferably wherein the content of nitrites is no more than 0.4 ppm, no more than 0.3 ppm, no more than 0.25 ppm, or no more than 0.2 ppm. The indicated step (a) of providing the composition may comprise a method of preparing ribociclib or pharmaceutically acceptable salt thereof as described elsewhere herein. For example, it may comprise a method of preparing ribociclib or pharmaceutically acceptable salt thereof that uses one or more solvents and (i) the total amount of nitrites in each of the one or more solvents is no more than 5 ppb, preferably no more than 3.5 ppb, and more preferably no more than 1 ppb, relative to the amount of the respective solvent; and / or (ii) the combined total amount of nitrites in the solvents is no more than 5 ppb, preferably no more than 3.5 ppb, and more preferably no more than 1 ppb, relative to the combined amount of the solvents. Following the step of drying the tablets, the tablets may be stored and / or packaged in a sealed container or blister pack as described elsewhere herein, optionally under an atmosphere in which the humidity is no more than 2.5 g / kg (or no more than 15% RH at 22.5°C). Preferably, the tablets may be stored and / or packaged in a substantially moisture and / or gas impermeable blister pack, for example such that each tablet is individually packaged within a substantially moisture and / or gas impermeable blister. Examples of substantially moisture and / or gas impermeable blister packs are provided elsewhere herein. Preferably, the substantially moisture and / or gas impermeable blister pack is an alu-alu blister pack. The tablets that result from the drying step, and in particular those that are subsequently stored and / or packaged in a sealed container or blister pack as described herein, such as those that are subsequently stored and / or packaged in a substantially moisture and / or gas impermeable blister pack, such as in a substantially moisture and / or gas impermeable blister pack as described herein, e.g., in an alu-alu blister pack, may have PAT059729-WO-PCT03 70 a shelf life as described herein. Preferably, they avoid the need for cold chain storage. More preferably, they have a shelf life of at least 18 months, and more preferably a shelf life of at least 24 months, when stored at a temperature of 20°C to 25°C. Another aspect of the invention provides a method of identifying a process for drying a pharmaceutical product comprising a plurality of oral dosage forms, wherein each of the oral dosage forms is a tablet, wherein said oral dosage forms comprise a composition comprising: (i) ribociclib or a pharmaceutically acceptable salt thereof; and (ii) one or more pharmaceutically acceptable excipients, wherein the process of drying comprises flowing an atmosphere (e.g., air) over the tablets, and wherein any one or any combination of the following parameters is adjusted until the process produces a product in which both: (1) the water activity value of the tablets is less than 0.2, for example wherein the water activity value of the tablets is no more than 0.18, no more than 0.16, no more than 0.14, no more than 0.12, less than 0.12, no more than 0.10, less than 0.10, no more than 0.08, less than 0.08, no more than 0.075, no more than 0.07, no more than 0.065, no more than 0.06, no more than 0.055, no more than 0.05, or no more than 0.045, preferably wherein the water activity is less than 0.08, more preferably no more than 0.06, and most preferably no more than 0.05; and (2) the total amount of nitrosamines in each of the tablets, or at least the total amount of N-nitroso- ribociclib in free or salt form in each of the tablets, is no more than 1 ppm, preferably no more than 0.7 ppm, and more preferably no more than 0.6 ppm, relative to the total amount of ribociclib in free or salt form, the said parameters being: a. the temperature at which the drying is conducted, optionally wherein the temperature is adjusted within the range of about 25 C to about 50 C, about 25 C to about 40 C, about 25 C to about35 C, or about 28 C to about 32 C, preferably wherein the temperature is adjusted within the range ofabout 25 C to about 35 C, more preferably within the range of about 28 C to about 32 C;b. the time period over which the drying is conducted, optionally wherein the time period is adjusted within the range of about 44 hours to about 72 hours, and preferably within the range of about 52 hours to about 64 hours, e.g., within the range of about 52 hours to about 60 hours, or within the range of about 54 hours to about 58 hours; c. the humidity of the atmosphere, optionally wherein the humidity is adjusted within the range of no more than 0.5 g / kg, preferably no more than 0.1 g / kg, and more preferably no more than 0.01 g / kg; d. the content of NOx species in the atmosphere, preferably wherein the content of NOx species in the atmosphere is reduced relative to the content of NOx species in the atmosphere before the adjustment; and e. the flow rate of the atmosphere, optionally wherein the flow rate is adjusted within the range of less than 3000 m3 / h, e.g., less than 2500 m3 / h, less than 2000 m3 / h, less than 1500 m3 / h, less than 1000 m3 / h, or less than 500 m3 / h, preferably wherein the flow rate of the atmosphere is less than 100 m3 / h. For example, the flow rate of the atmosphere may be about 20 to about 100 m3 / h, about 20 to PAT059729-WO-PCT03 71 about 75 m3 / h, about 20 to about 50 m3 / h, about 25 to about 40 m3 / h, about 26 to about 35 m3 / h, or about 28 to about 30 m3 / h, preferably wherein the flow rate of the atmosphere is about 28 to about 30 m3 / h. The invention further provides a tablet comprising (i) ribociclib or a pharmaceutically acceptable salt thereof; and (ii) one or more pharmaceutically acceptable excipients, wherein the tablet has a water activity value of less than 0.08, preferably no more than 0.06, and more preferably no more than 0.05. The total amount of nitrosamines in the tablet, or at least the total amount of N-nitroso-ribociclib in free or salt form in the tablet, may be no more than 1 ppm, preferably no more than 0.7 ppm, and more preferably no more than 0.6 ppm, relative to the total amount of ribociclib in free or salt form. Examples of suitable excipients, combinations of excipients, amounts of excipients, amounts of nitrites within the excipients, and amounts of nitrites within the tablet are described elsewhere herein. An aspect of the invention relates to a method of preparing a pharmaceutical product comprising a plurality of oral dosage forms as described herein, wherein the method comprises sealing the oral dosage forms individually or together in a container under an atmosphere in which the percentage of oxygen is less than 21% by volume. The atmosphere may be an inert gas such as helium, nitrogen, argon, or neon. Preferably, the atmosphere is nitrogen. An aspect of the invention relates to a method of preparing a pharmaceutical product comprising a plurality of oral dosage forms as described herein, wherein the method comprises sealing the oral dosage forms individually or together in a container which also contains a desiccant, or sealing the oral dosage forms together in a pharmaceutical package which also contains a desiccant in a separate container. The desiccant may be selected from the following list: activated alumina, aerogel, benzophenone, bentonite clay, calcium chloride, calcium oxide, calcium sulphate, cobalt(II) chloride, copper(II) sulphate, lithium chloride, lithium bromide, magnesium chloride hexahydrate, magnesium sulphate, magnesium perchlorate, molecular sieve, phosphorus pentoxide, potassium carbonate, potassium hydroxide, rice, silica gel, sodium, sodium chlorate, sodium chloride, sodium hydroxide, sodium sulphate, sucrose, sulfuric acid, triethylene glycol, and zeolite. Preferably, the desiccant is selected from the group consisting of silica gel, molecular sieve, calcium oxide, and calcium sulphate. More preferably, the desiccant is silica gel. An aspect of the invention relates to a method of preparing a pharmaceutical product comprising a plurality of oral dosage forms as described herein, wherein the method comprises incorporating in each of the oral dosage forms one or more pharmaceutically acceptable additives which prevent, retard or reduce the formation of N- nitroso-ribociclib in free or salt form. Each of the one or more additives may be selected from the group consisting of pH adjusters, antioxidants, radical scavenging agents, and peroxide-quenching agents. PAT059729-WO-PCT03 72 An aspect of the invention relates to a method of preparing a pharmaceutical product comprising a plurality of oral dosage forms as described herein, wherein the method comprises sealing the oral dosage forms individually or together in a container under an atmosphere in which the humidity is no more than 2.5 g / kg (or a relative humidity of no more than 15%). The oral dosage forms may be sealed within a blister pack such that each oral dosage form is individually sealed within a substantially moisture and / or gas impermeable blister, e.g., they may be sealed within a substantially moisture and / or gas impermeable blister pack as described herein, preferably within an alu-alu blister pack. In any of these aspects, which may be used in any combination, the plurality of oral dosage forms may be a plurality of tablets. The invention further provides a process for preparing a composition comprising or consisting of ribociclib or a pharmaceutically acceptable salt thereof, wherein the process has been determined to consistently produce a composition which satisfies a requirement as specified herein for the amount of total nitrosamines in such a composition and / or the total amount of N-nitroso-ribociclib in free or salt form in such a composition. For example, the process may have been determined to consistently produce a composition in which the total amount of N-nitroso-ribociclib in free or salt form and / or the amount of total nitrosamines (including both N- nitroso-ribociclib in free or salt form and other nitrosamines) is no more than 1ppm, preferably no more than 0.7 ppm, more preferably no more than 0.6 ppm, or even more preferably no more than 0.4 ppm, relative to the total amount of ribociclib in free or salt form. The composition may further comprise one or more pharmaceutically acceptable excipients. Examples of suitable excipients, combinations of excipients, and amounts of excipients are as described elsewhere herein. The invention further provides a process for preparing a pharmaceutical product comprising a composition that comprises: (i) ribociclib or a pharmaceutically acceptable salt thereof; and (ii) one or more pharmaceutically acceptable excipients, wherein the process has been determined to consistently produce a composition which satisfies a requirement as specified herein for the amount of total nitrosamines in such a composition and / or the total amount of N-nitroso-ribociclib in free or salt form in such a composition. For example, the process may have been determined to consistently produce a composition in which the total amount of N-nitroso- ribociclib in free or salt form and / or the amount of total nitrosamines (including both N-nitroso-ribociclib in free or salt form and other nitrosamines) is no more than 1 ppm, preferably no more than 0.7 ppm, more preferably no more than 0.6 ppm, or even more preferably no more than 0.4 ppm, relative to the total amount of ribociclib in free or salt form. As with the above process, examples of suitable excipients, combinations of excipients, and amounts of excipients are as described elsewhere herein. These processes may be used in the preparation of a pharmaceutical product comprising a plurality of oral dosage forms as described herein, e.g., a plurality of tablets, wherein the processes may have been determined to consistently produce a plurality of oral dosage forms in which the total amount of N-nitroso- PAT059729-WO-PCT03 73 ribociclib in free or salt form and / or the amount of total nitrosamines (including both N-nitroso-ribociclib in free or salt form and other nitrosamines) in each of the oral dosage forms is no more than 1 ppm, preferably no more than 0.7 ppm, more preferably no more than 0.6 ppm, or even more preferably no more than 0.4 ppm, relative to the total amount of ribociclib in free or salt form. Corresponding processes which have been determined to consistently produce a composition (e.g., a plurality of oral dosage forms) which, in addition to satisfying a requirement as specified herein for the amount of total nitrosamines and / or the total amount of N-nitroso-ribociclib in free or salt form, also satisfies a requirement as specified herein for the total amount of nitrites, are also provided. The determination that a particular process consistently produces a composition which satisfies a requirement as specified herein for the amount of total nitrosamines and / or the total amount of N-nitroso-ribociclib in free or salt form in such a composition may be reflected in the fact that the composition that is obtainable by the process has been approved by a regulatory authority, such as the FDA, the EMA, the MHRA, Swissmedic, or the PMDA. As such, the above-mentioned references to a process which has been determined to consistently produce a composition which satisfies a requirement as specified herein for the amount of total nitrosamines and / or the total amount of N-nitroso-ribociclib in free or salt form in such a composition can alternatively be expressed as a process for preparing a composition (or a pharmaceutical product comprising a composition) which comprises or consists of ribociclib or a pharmaceutically acceptable salt thereof and, optionally, one or more pharmaceutically acceptable excipients, wherein said composition: (a) satisfies a requirement as specified herein for the amount of total nitrosamines and / or the total amount of N-nitroso-ribociclib in free or salt form in such a composition; and (b) is a composition that is approved by a regulatory authority, such as the FDA, the EMA, the MHRA, Swissmedic, or the PMDA. Any such approval may be one that takes account of the amount of total nitrosamines and / or the total amount of N-nitroso-ribociclib in free or salt form in such a composition. The approval may be one issued subsequently to the publication of the FDA document entitled Control of Nitrosamine Impurities in Human Drugs, Guidance for Industry, U.S. Department of Health and Human Services, Food and Drug Administration, February 2021, Revision 1 and / or the EMA document entitled European Medicines Regulatory Network approach for the implementation of the CHMP Opinion pursuant to Article 5(3) of Regulation (EC) No 726 / 2004 for nitrosamine impurities in human medicines, EMA / 425645 / 2020, 22 February 2021. Storage of the Drug Substance / Drug Product The invention further provides methods of storing the ribociclib or pharmaceutically acceptable salt thereof, as well as methods of storing the pharmaceutical compositions comprising (i) ribociclib or a pharmaceutically acceptable salt thereof and (ii) one or more pharmaceutically acceptable excipients. These methods may be used to prevent, retard or reduce the formation of nitrosamines, in particular N-nitroso-ribociclib in free or salt form. PAT059729-WO-PCT03 Storage of the Drug Substance An aspect of the invention relates to a method of storing a composition comprising or consisting of ribociclib or a pharmaceutically acceptable salt thereof, wherein the method comprises storing the composition in the presence of a desiccant, e.g., storing the composition in a sealed container which also contains a desiccant, or storing the composition in a sealed pharmaceutical package which also contains a desiccant, optionally in a separate container. The method may further comprise testing the composition for the presence and / or amount of nitrosamines (such as the presence and / or total amount of N-nitroso-ribociclib in free or salt form). The method may comprise testing the composition for the presence and / or amount of nitrites. The desiccant may be used to prevent, retard or reduce the formation of nitrosamines (such as N-nitroso- ribociclib and / or salts thereof) in a composition comprising or consisting of ribociclib or a pharmaceutically acceptable salt thereof. For example, the composition comprising or consisting of ribociclib may be stored in the presence of a desiccant, e.g., the composition may be stored in a sealed container which also contains a desiccant, or the composition may be stored in a sealed pharmaceutical package which also contains a desiccant, optionally in a separate container. Thus, an aspect of the invention relates to the use of a desiccant for preventing, retarding or reducing the formation of nitrosamines (such as N-nitroso-ribociclib or salts thereof) in a composition comprising or consisting of ribociclib or a pharmaceutically acceptable salt thereof, wherein the use comprises storing the composition in the presence of the desiccant, e.g., storing the composition in a sealed container which also contains a desiccant, or storing the composition in a sealed pharmaceutical package which also contains a desiccant, optionally in a separate container. The desiccant may be selected from the following list: activated alumina, aerogel, benzophenone, bentonite clay, calcium chloride, calcium oxide, calcium sulphate, cobalt(II) chloride, copper(II) sulphate, lithium chloride, lithium bromide, magnesium chloride hexahydrate, magnesium sulphate, magnesium perchlorate, molecular sieve, phosphorus pentoxide, potassium carbonate, potassium hydroxide, rice, silica gel, sodium, sodium chlorate, sodium chloride, sodium hydroxide, sodium sulphate, sucrose, sulfuric acid, triethylene glycol, and zeolite. Preferably, the desiccant may be selected from silica gel, molecular sieve, calcium oxide, and calcium sulphate. More preferably, the desiccant may be silica gel. Examples of how the desiccant may be included in or incorporated into the sealed container or sealed pharmaceutical package are described elsewhere herein. Another aspect of the invention relates to a method of storing a composition comprising or consisting of ribociclib or a pharmaceutically acceptable salt thereof, wherein the method comprises storing the composition under an atmosphere in which the percentage of oxygen is less than 21% by volume. Thus, an aspect of the invention is the use of an atmosphere in which the percentage of oxygen is less than 21% by volume for preventing, retarding or reducing the formation of nitrosamines (such as N-nitroso-ribociclib in free or salt form) in a composition comprising or consisting of ribociclib or a pharmaceutically acceptable salt thereof, wherein PAT059729-WO-PCT03 75 the composition is stored under the atmosphere. The atmosphere may be an inert gas such as helium, nitrogen, argon, or neon. Preferably, the atmosphere is nitrogen. Once again, these methods, like any of the methods of storage that are described herein, may further comprise testing the composition comprising or consisting of ribociclib or a pharmaceutically acceptable salt thereof for the presence and / or amount of nitrosamines (such as the presence and / or total amount of N-nitroso-ribociclib in free or salt form). The method of testing for the presence and / or amount of nitrosamines (such as the presence and / or total amount of N-nitroso-ribociclib in free or salt form) as used in the methods of the invention may be the Griess test. Alternatively, the method of testing for the presence and / or total amount of nitrosamines (such as the presence and / or total amount of N-nitroso-ribociclib in free or salt form) as used in the methods of the invention may be high performance liquid chromatography (HPLC)- and / or gas chromatography (GC)-mass spectroscopy. Testing for the presence and / or amount of nitrosamines (such as the presence and / or total amount of N- nitroso-ribociclib in free or salt form) may have particular utility in the context of a method of evaluating the stability of a composition comprising ribociclib or a pharmaceutically acceptable salt thereof, such as a pharmaceutical composition comprising (i) ribociclib or a pharmaceutically acceptable salt thereof and (ii) one or more pharmaceutically acceptable excipients. Such a method of evaluating the stability of a composition comprising ribociclib or a pharmaceutically acceptable salt thereof provides a further aspect of the invention. In such methods, the impact during storage of the composition on the formation of nitrosamines, or at least on the formation of N-nitroso-ribociclib in free or salt form, of one or more parameters may be evaluated. Such parameters may be selected from (a) storage conditions such as temperature, humidity, atmosphere, the presence of a desiccant, and / or the duration of storage or (b) the presence of one or more additives or pharmaceutically acceptable excipients in the composition, e.g., excipients which have been selected for their low concentration of nitrites. Various parameters which have been shown herein to have an impact on the formation of nitrosamines (such as N-nitroso-ribociclib in free or salt form) in a composition comprising ribociclib or a pharmaceutically acceptable salt thereof are described elsewhere herein. The testing for the presence and / or amount of nitrosamines (such as the presence and / or total amount of N-nitroso-ribociclib in free or salt form) may occur at the start of the storage, at the end of the storage, or both at the start and at the end of the storage. The results of such a method of evaluating the stability of a composition comprising ribociclib or a pharmaceutically acceptable salt thereof may be submitted to a regulatory authority. Another aspect of the invention relates to a method of storing a composition comprising or consisting of ribociclib or a pharmaceutically acceptable salt thereof, wherein the method comprises storing the compositionat a temperature of less than 40 C, or less than 30 C, or less than 25 C, or less than 20 C, or between about 1to about 10 C. In some aspects, the composition is stored at about 2 to about 8 C. In some aspects, thecomposition is stored at about 4 to about 6 C. In some aspects, the composition is stored at about 5 C. In otheraspects, the composition is stored at about 20 C to about 25 C. The method may further comprise storing the PAT059729-WO-PCT03 76 composition under relative humidity conditions of less than 75%, less than 60%, or no more than 15%. The method may further comprise testing the composition for the presence and / or amount of nitrosamines, such as the presence and / or total amount of N-nitroso-ribociclib in free or salt form.The method may comprise storing the composition at a temperature of between about 1 to about 10 C (suchas at about 2 to about 8 C, at about 4 to about 6 C, or at about 5 C) or at room temperature (such as at about20 C to about 35 C, e.g., at about 20 C to about 25 C).Storage of the Drug Product Another aspect of the invention relates to a method of storing a composition comprising (i) ribociclib or a pharmaceutically acceptable salt thereof and (ii) one or more pharmaceutically acceptable excipients, whereinthe method comprises storing the composition at a temperature of about 1 to about 10 C. In some aspects,the composition is stored at about 2 to about 8 C. In some aspects, the composition is stored at about 4 toabout 6 C. In some aspects, the composition is stored at about 5 C. The method may further comprise testingthe composition for the presence and / or amount of nitrosamines, such as the presence and / or total amount of N-nitroso-ribociclib in free or salt form. The method may further comprise storing the composition under relative humidity conditions of less than 75%, or less than 60%, preferably wherein the relative humidity is no more than 15%.The method may comprise storing the composition at a temperature of between about 1 to about 10 C (suchas at about 2 to about 8 C, at about 4 to about 6 C, or at about 5 C).The method may comprise storing the composition at a first temperature, followed by storing the composition at a second temperature. For example, the composition may be stored at a first temperature when it, or any other composition that is present in the same container or with which it is packaged, is not in use, followed by storage at a second temperature once the composition, or the respective other composition, is in use (e.g., when packaging containing the drug product, such as a sealed pharmaceutical package containing a plurality of dosage forms, such as a plurality of orally administrable tablets, has been opened). The first temperaturemay be between about 1 to about 10 C (such as at about 2 to about 8 C, at about 4 to about 6 C, or at about5 C). The second temperature may be at room temperature (such as at about 20 C to about 25 C). Therefore,the composition may be stored at about 2 to about 8 C when it or said any other composition is not in use, andthen stored at about 20 C to about 25 C once it or the respective other composition is in use (i.e., when thepackaging containing the drug product has been opened). An alternative aspect of the invention relates to a method of storing a composition comprising (i) ribociclib or a pharmaceutically acceptable salt thereof and (ii) one or more pharmaceutically acceptable excipients,wherein the method comprises storing the composition at a temperature of about 20 C to about 25 C. The PAT059729-WO-PCT03 77 method may further comprise testing the composition for the presence and / or amount of nitrosamines, such as the presence and / or total amount of N-nitroso-ribociclib in free or salt form. The method may further comprise storing the composition under relative humidity conditions of less than 75%, or less than 60%, preferably wherein the relative humidity is no more than 15%. The composition comprising (i) ribociclib or a pharmaceutically acceptable salt thereof and (ii) one or more pharmaceutically acceptable excipients may be stored under an atmosphere in which the percentage of oxygen is less than 21% by volume. The atmosphere may be an inert gas such as helium, nitrogen, argon, or neon. Preferably, the atmosphere is nitrogen. The composition comprising (i) ribociclib or a pharmaceutically acceptable salt thereof and (ii) one or more pharmaceutically acceptable excipients may be stored in the presence of a desiccant, e.g., the composition may be stored in a sealed container which also contains a desiccant, or the composition may be stored in a sealed pharmaceutical package which also contains a desiccant, optionally in a separate container. The desiccant may be selected from the following list: activated alumina, aerogel, benzophenone, bentonite clay, calcium chloride, calcium oxide, calcium sulphate, cobalt(II) chloride, copper(II) sulphate, lithium chloride, lithium bromide, magnesium chloride hexahydrate, magnesium sulphate, magnesium perchlorate, molecular sieve, phosphorus pentoxide, potassium carbonate, potassium hydroxide, rice, silica gel, sodium, sodium chlorate, sodium chloride, sodium hydroxide, sodium sulphate, sucrose, sulfuric acid, triethylene glycol, and zeolite. Preferably, the desiccant may be selected from silica gel, molecular sieve, calcium oxide, and calcium sulphate. More preferably, the desiccant may be silica gel. Another aspect of the invention relates to a method of evaluating the storage stability of a composition comprising (i) ribociclib or a pharmaceutically acceptable salt thereof and (ii) one or more pharmaceutically acceptable excipients, wherein the method comprises storing the composition for a predetermined period of time under a predetermined set of conditions. The method may further comprise testing the composition for the presence and / or amount of nitrosamines, such as the presence and / or total amount of N-nitroso-ribociclib in free or salt form. The testing may occur at the start of the predetermined period of time, at the end of the predetermined period of time, or both at the start and end of the predetermined period of time. It may also occur at one or more intermediate time points during the predetermined period of time. The predetermined period of time may be 2 weeks, 1 month, 2 months, 3 months, 5 months, 6 months, 9 months, 12 months, 18 months, 24 months, or 36 months. The predetermined period of time may be 1 month, 2 months, 3 months, 5 months, or 6 months, for example 1 month, 3 months, or 6 months. The predetermined set of conditions may be (i) a temperature of 25oC, 30oC, 40oC, or 50oC and (ii) RH of 60%. Alternatively, the predetermined set of conditions may be (i) a temperature of 25oC, 30oC, 40oC, or 50oC and (ii) RH of 75%. The predetermined set of conditions may be 25oC / 60% RH, 30oC / 75% RH, 40oC / 75% RH, or 50oC / 75% RH, PAT059729-WO-PCT03 78 for example 30oC / 75% RH, 40oC / 75% RH or 50oC / 75% RH. For example, the predetermined period of time and set of conditions may be: (i) 2 weeks at 30oC / 75%; (ii) 1 month at 30oC / 75%; (iii) 3 months at 30oC / 75%; (iv) 6 months at 30oC / 75%; (v) 2 weeks at 40oC / 75%; (vi) 1 month at 40oC / 75%; (vii) 3 months at 40oC / 75%; (viii) 6 months at 40oC / 75%; (ix) 2 weeks at 50oC / 75%; (x) 1 month at 50oC / 75%; (xi) 3 months at 50oC / 75%; and / or (xii) 6 months at 50oC / 75%; The composition comprising (i) ribociclib or a pharmaceutically acceptable salt thereof and (ii) one or more pharmaceutically acceptable excipients may be present in a pharmaceutical product which further comprises a document providing instructions to a patient as to how to administer the composition. Another aspect of the invention relates to a method of storing over a period of time a composition comprising or consisting of ribociclib or a pharmaceutically acceptable salt thereof, wherein the total amount of N-nitroso- ribociclib in free or salt form in the composition at the start of the period of time is no more than a first threshold amount, and wherein the total amount of N-nitroso-ribociclib in free or salt form in the composition at the end of the period of time is no more than a second threshold amount, wherein the storing of the composition incorporates means to prevent, retard or reduce the formation of N-nitroso-ribociclib in free or salt form. The means to prevent, retard or reduce the formation of N-nitroso-ribociclib in free or salt form may comprise or consist of one or any combination of the following: a. storing the composition in a sealed container under an atmosphere in which the percentage of oxygen is less than 21% by volume. The atmosphere may be an inert gas such as helium, nitrogen, argon, or neon. Preferably, the atmosphere is nitrogen; b. storing the composition in a sealed container which also contains a desiccant, or storing the composition in a sealed pharmaceutical package which also contains a desiccant in a separate container. The desiccant may be selected from the following list: activated alumina, aerogel, benzophenone, bentonite clay, calcium chloride, calcium oxide, calcium sulphate, cobalt(II) chloride, copper(II) sulphate, lithium chloride, lithium bromide, magnesium chloride hexahydrate, PAT059729-WO-PCT03 79 magnesium sulphate, magnesium perchlorate, molecular sieve, phosphorus pentoxide, potassium carbonate, potassium hydroxide, rice, silica gel, sodium, sodium chlorate, sodium chloride, sodium hydroxide, sodium sulphate, sucrose, sulfuric acid, triethylene glycol, and zeolite. Preferably, the desiccant may be selected from silica gel, molecular sieve, calcium oxide, and calcium sulphate. More preferably, the desiccant may be silica gel; c. storing the composition under an atmosphere in which the relative humidity is less than 75 %, optionally wherein the relative humidity is less than 60 %, preferably wherein the relative humidity is no more than 15 %; d. storing the composition at a temperature of less than about 25 C. The composition may be storedat a temperature of between about 1 to about 10 C (such as at about 2 to about 8 C, at about 4 toabout 6 C, or at about 5 C) or it may be stored at room temperature (such as at about 20 C to lessthan about 25 C);e. storing the composition in a sealed container under an atmosphere in which the humidity is no more than 2.5 g / kg, optionally wherein the composition is provided as a plurality of oral dosage forms that are packaged within a blister pack such that each oral dosage form is individually packaged within a substantially moisture and / or gas impermeable blister; f. incorporating in the composition one or more pharmaceutically acceptable additives which prevent, retard or reduce the formation of N-nitroso-ribociclib in free or salt form, optionally wherein each of the one or more additives is selected from the group consisting of pH adjusters, antioxidants, radical scavenging agents, and peroxide-quenching agents. The period of time may be at least 1, at least 2, at least 3, at least 4, at least 5, at least 6, at least 7, at least 8, at least 9, at least 10, at least 11, at least 12, at least 13, at least 14, at least 15, at least 16, at least 17, at least 18, at least 24, at least 30, at least 36, at least 42, at least 48, at least 54 or at least 60 months, preferably wherein the period of time is at least 12 months, more preferably wherein the period of time is at least 18 months, most preferably wherein the period of time is at least 24 months, for example at least 36 months, at least 48 months, or at least 60 months. The first threshold amount may be about 5 ppm, for example about 4 ppm, about 3 ppm, about 2 ppm, or about 1 ppm. For example, the first threshold amount may be about 0.9 ppm, about 0.8 ppm, about 0.7 ppm, about 0.65 ppm, about 0.6 ppm, about 0.55 ppm, about 0.5 ppm, about 0.45 ppm, about 0.4 ppm, about 0.35 ppm, about 0.3 ppm, about 0.25 ppm, about 0.2 ppm, about 0.15 ppm, about 0.1 ppm, about 0.05 ppm, or about 0.025 ppm. Preferably, the first threshold amount may be about 0.7 ppm, for example about 0.6 ppm, or about 0.4 ppm. PAT059729-WO-PCT03 80 The second threshold amount may be about 5 ppm, for example about 4 ppm, about 3 ppm, about 2 ppm, or about 1 ppm. Preferably, the second threshold amount may be about 1 ppm. For example, the second threshold amount may be about 0.9 ppm, about 0.8 ppm, about 0.7 ppm, about 0.65 ppm, about 0.6 ppm, about 0.55 ppm, about 0.5 ppm, about 0.45 ppm, about 0.4 ppm, about 0.35 ppm, about 0.3 ppm, about 0.25 ppm, about 0.2 ppm, about 0.15 ppm, about 0.1 ppm, about 0.05 ppm, or about 0.025 ppm. The second threshold amount may be no more than 1.5 ppm greater than the first threshold amount, for example no more than 1, no more than 0.9, no more than 0.8, no more than 0.7, no more than 0.6, no more than 0.5 or no more than 0.4 ppm greater than the first threshold amount. The second threshold amount may no more than 200% of the first threshold amount, for example no more than 190, no more than 180, no more than 170, no more than 160, no more than 150, no more than 140, no more than 130, no more than 120 or no more than 110% of the first threshold amount. Optionally, the first and second threshold amounts are the same. In such methods involving storing or evaluating the stability of a composition comprising ribociclib or a pharmaceutically acceptable salt thereof, the composition may be a pharmaceutical composition as described herein. For example, the composition may comprise one or more pharmaceutically acceptable excipients, wherein the one or more pharmaceutically acceptable excipients may be as described herein. The composition may be an oral dosage form. For example, the composition may be a tablet. The composition may be part of a pharmaceutical product as described herein, such as a pharmaceutical product comprising a plurality of oral dosage forms. The composition may be part of a pharmaceutical product which further comprises one or more of: a. a document providing, either directly or via a link to an electronic database, instructions to a patient as to how to administer the composition; b. a document providing, either directly or via a link to an electronic database, instructions which specify how the composition should be stored; c. a document which, either directly or via a link to an electronic database, indicates that, provided that the composition is stored in accordance with specified instructions, the total amount of N- nitroso-ribociclib in free or salt form in the composition will be no more than the second threshold amount. The method may comprise a step of determining the total amount of N-nitroso-ribociclib in free or salt form in the composition. The step of determining the total amount of N-nitroso-ribociclib in free or salt form in the composition may be performed by a method which includes the Griess test and / or high performance liquid chromatography (HPLC)-mass spectroscopy and / or gas chromatography (GC)-mass spectroscopy, as described elsewhere herein. PAT059729-WO-PCT03 81 A related aspect of the invention relates to corresponding methods of storing over a period of time a composition comprising or consisting of ribociclib or a pharmaceutically acceptable salt thereof, wherein the total amount of nitrosamines in the composition at the start of the period of time is no more than the first threshold amount, and wherein the total amount of nitrosamines in the composition at the end of the period of time is no more than the second threshold amount, i.e., the references to N-nitroso-ribociclib in free or salt form should each be read as a reference to nitrosamines. Shelf Life Another aspect of the invention relates to a composition comprising ribociclib or a pharmaceutically acceptable salt thereof, wherein the composition has a shelf life of at least 1, at least 2, at least 3, at least 4, at least 5, at least 6, at least 7, at least 8, at least 9, at least 10, at least 11, at least 12, at least 13, at least 14, at least 15, at least 16, at least 17, at least 18, at least 24, at least 30, at least 36, at least 42, at least 48, at least 54 or atleast 60 months when stored at a temperature of no more than 40 C. Preferably the shelf life is at least 18months, and more preferably at least 24 months.The shelf life may be under storage at a temperature of about 2 to about 8 C, for example at a temperature ofabout 4 to about 6 C or at about 5 C. The shelf life may be under storage at a temperature of no more thanabout 30 C, optionally at a temperature of no more than about 25 C, for example at a temperature of no morethan about 20 C to about 25 C, such as a temperature of no more than about 20 C, no more than about 21 C,no more than about 22 C, no more than about 23 C, no more than about 24 C or no more than about 25 C.The shelf life may be at least 24 months, for example at least 36 months, at least 48 months, or at least 60months. The shelf life may be at least 12 months under storage at a temperature of about 2 to about 8 C, forexample at a temperature of about 4 to about 6 C or at about 5 C. For example, the shelf life may be at least18 months under storage of about 2 to about 8 C, for example at a temperature of about 4 to about 6 C or atabout 5 C. Alternatively, the shelf life may be at least 24 months under storage at a temperature of no morethan about 30 C, for example at least 36 months under storage at a temperature of no more than about 20 Cto about 25 C. Preferably, the shelf life is at least 18 months, more preferably at least 24 months, under storageat a temperature of no more than about 20 C to about 25 C.The shelf life storage conditions may differ depending on the stage of drug usage, for example depending on whether the drug product packaging has been opened and is in use, as described elsewhere herein. In one aspect, a first shelf life is provided for storage of the composition comprising ribociclib or a pharmaceutically acceptable salt thereof when it, or any other composition that is present in the same container or with which it is packaged, is not in use, followed by a second shelf life for storage of the composition when it, or the respective other composition, is in use. The first shelf life may be under storage at a temperature of about 2 toabout 8 C, for example at a temperature of about 4 to about 6 C or at about 5 C. The first shelf life may be atleast 10 months, e.g., at least 11, at least 12, at least 13, at least 14, at least 15, at least 16, at least 17, at least 18, at least 24, at least 30, at least 36, at least 42, at least 48, at least 54 or at least 60 months. The PAT059729-WO-PCT03 82second shelf life may be under storage at a temperature of no more than about 30 C, optionally at atemperature of no more than about 25 C, for example at a temperature of no more than about 20 C to about25 C. The second shelf life may be least 1 month, e.g., at least 2, at least 3, at least 4, at least 5, at least 6, atleast 7, at least 8, or at least 9 months. Preferably, the second shelf life is at least 2 months. In a preferredaspect, the first shelf life is at least 10 months under storage at a temperature of about 2 to about 8 C, and thesecond shelf life is at least 2 months under storage at a temperature of no more than about 20 C to about25 C. In preferred embodiments, the second shelf life is at least 18 months, and more preferably at least 24months, under storage at a temperature of 20 C to about 25 C.The shelf life may be the period of time in which the total amount of nitrosamines (such as N-nitroso-ribociclib in free or salt form) in the composition remains no more than about 5 ppm, for example no more than about 4 ppm, no more than about 3 ppm, no more than about 2 ppm, or no more than about 1 ppm. Preferably, the shelf life may be the period of time in which the total amount of nitrosamines (such as N-nitroso-ribociclib in free or salt form) in the composition remains no more than about 1 ppm. In some aspects, the shelf life may be the period of time in which the total amount of nitrosamines (such as N-nitroso-ribociclib in free or salt form) in the composition remains no more than about 0.9 ppm, no more than about 0.8 ppm, no more than about 0.7 ppm, no more than about 0.6 ppm, no more than about 0.5 ppm, no more than about 0.4 ppm, no more than about 0.3 ppm, no more than about 0.2 ppm, no more than about 0.1 ppm, no more than about 0.05 ppm, or no more than about 0.025 ppm. Preferably, the shelf life may be the period of time in which the total amount of nitrosamines (such as N-nitroso-ribociclib in free or salt form) in the composition remains no more than about 0.7 ppm, for example no more than 0.6 ppm. This period of time may be at least 1, at least 2, at least 3, at least 4, at least 5, at least 6, at least 7, at least 8, at least 9, at least 10, at least 11, at least 12, at least 13, at least 14, at least 15, at least 16, at least 17, at least 18, at least 24, at least 30, at least 36, at least 42, at least 48, at least 54 or at least 60 months. For example, the total amount of nitrosamines (such as N-nitroso- ribociclib in free or salt form) in the composition may remain no more than about 1 ppm for at least 9 months, for example no more than 0.7 ppm or no more than 0.6 ppm for at least 9 months. Preferably, the total amount of nitrosamines (such as N-nitroso-ribociclib in free or salt form) in the composition may remain no more than about 1 ppm for at least 9 months (for example no more than 0.7 ppm or no morethan 0.6 ppm for at least 9 months) when the composition is stored at a temperature of no more than 40 C, orno more than about 25 C, or between about 2 to about 8 C. In one aspect, the total amount of nitrosamines(such as N-nitroso-ribociclib in free or salt form) in the composition may remain no more than about 1 ppm (for example no more than 0.7 ppm or no more than 0.6 ppm) for at least 10 months when the composition isstored at a temperature of between about 2 to about 8 C. In another aspect, the total amount of nitrosamines(such as N-nitroso-ribociclib in free or salt form) in the composition may remain no more than about 1 ppm (for example no more than 0.7 ppm or no more than 0.6 ppm) for at least 2 months when the composition is storedat a temperature of between about 20 C to about 25 C. In a preferred aspect, the total amount of nitrosamines(such as N-nitroso-ribociclib in free or salt form) in the composition may remain no more than about 1 ppm (for PAT059729-WO-PCT03 83 example no more than 0.7 ppm or no more than 0.6 ppm) when stored for at least 10 months at a temperatureof between about 2 to about 8 C, followed by at least 2 months when stored at a temperature of between about20 C to about 25 C.In highly preferred embodiments, the total amount of nitrosamines (or at least the total amount of N-nitroso- ribociclib in free or salt form) in the composition remains no more than about 1 ppm for at least 18 months (for example no more than 0.7 ppm, or no more than 0.6 ppm for at least 18 months) when the composition isstored at a temperature of no more than about 25 C. In even more highly preferred embodiments, the totalamount of nitrosamines (or at least the total amount of N-nitroso-ribociclib in free or salt form) in the composition remains no more than about 1 ppm (for example no more than 0.7 ppm, or no more than 0.6 ppm)for at least 24 months when the composition is stored at a temperature of between about 20 to about 25 C.The shelf life may be the period of time in which the total amount of nitrosamines (such as N-nitroso-ribociclib in free or salt form) in the composition remains no more than an amount which would result in an amount of said nitrosamines (such as N-nitroso-ribociclib in free or salt form) that corresponds to an amount of 400 ng / day of nitrosamine free base (such as N-nitroso-ribociclib free base) being administered to the patient when the composition is administered according to an approved dosage regimen of ribociclib or pharmaceutically acceptable salt thereof. This period of time may be at least 1, at least 2, at least 3, at least 4, at least 5, at least 6, at least 7, at least 8, at least 9, at least 10, at least 11, at least 12, at least 13, at least 14, at least 15, at least 16, at least 17, at least 18, at least 24, at least 30, at least 36, at least 42, at least 48, at least 54 or at least 60 months, for example at least 9 months or at least 10 months, preferably at least 18 months, and more preferably at least 24 months. The shelf life may be the period of time in which the total amount of N-nitroso-ribociclib in free or salt form in the composition remains no more than about 5 ppm, relative to the total amount of ribociclib in free or salt form, for example no more than about 4 ppm, no more than about 3 ppm, no more than about 2 ppm, or no more than about 1 ppm, relative to the total amount of ribociclib in free or salt form. Preferably, the shelf life may be the period of time in which the total amount of N-nitroso-ribociclib in free or salt form in the composition remains no more than about 1 ppm, relative to the total amount of ribociclib in free or salt form. In some aspects, the shelf life may be the period of time in which the total amount of N-nitroso-ribociclib in free or salt form in the composition remains no more than about 0.9 ppm, no more than about 0.8 ppm, no more than about 0.7 ppm, no more than about 0.6 ppm, no more than about 0.5 ppm, no more than about 0.4 ppm, no more than about 0.3 ppm, no more than about 0.2 ppm, no more than about 0.1 ppm, no more than about 0.05 ppm, or no more than about 0.025 ppm, relative to the total amount of ribociclib in free or salt form. In a preferred aspect, the shelf life may be the period of time in which the total amount of N-nitroso-ribociclib in free or salt form in the composition remains no more than about 0.7 ppm, for example no more than 0.6 ppm, relative to the total amount of ribociclib in free or salt form. This period of time may be at least 1, at least 2, at least 3, at least 4, at least 5, at least 6, at least 7, at least 8, at least 9, at least 10, at least 11, at least 12, at PAT059729-WO-PCT03 84 least 13, at least 14, at least 15, at least 16, at least 17, at least 18, at least 24, at least 30, at least 36, at least 42, at least 48, at least 54 or at least 60 months. Preferably, this period of time is at least 18 months, more preferably at least 24 months. In one example, the total amount of N-nitroso-ribociclib in free or salt form in the composition may remain no more than about 1 ppm, relative to the total amount of ribociclib in free or salt form, for at least 9 months, e.g., for at least 10 months, preferably for at least 18 months, and more preferably for at least 24 months. In another example, the total amount of N-nitroso-ribociclib in free or salt form in the composition may remain no more than about 0.7 ppm, relative to the total amount of ribociclib in free or salt form, for at least 9 months, e.g., for at least 10 months, preferably for at least 18 months, and more preferably for at least 24 months. In a third example, the total amount of N-nitroso-ribociclib in free or salt form in the composition may remain no more than about 0.6 ppm, relative to the total amount of ribociclib in free or salt form, for at least 9 months, e.g., for at least 10 months, preferably for at least 18 months, and more preferably for at least 24 months. The shelf life may be the period of time in which the total amount of N-nitroso-ribociclib in free or salt form in the composition remains no more than an amount which would result in an amount of said N-nitroso-ribociclib in free or salt form that corresponds to an amount of 400 ng / day of N-nitroso-ribociclib free base being administered to the patient when the composition is administered according to an approved dosage regimen of ribociclib or pharmaceutically acceptable salt thereof. This period of time may be at least 1, at least 2, at least 3, at least 4, at least 5, at least 6, at least 7, at least 8, at least 9, at least 10, at least 11, at least 12, at least 13, at least 14, at least 15, at least 16, at least 17, at least 18, at least 24, at least 30, at least 36, at least 42, at least 48, at least 54 or at least 60 months, for example at least 9 months or at least 10 months, preferably at least 18 months, and more preferably at least 24 months. The invention also provides a composition comprising ribociclib or a pharmaceutically acceptable salt thereof, wherein the amount of nitrosamines (such as N-nitroso-ribociclib in free or salt form) in the composition is no more than about 5 ppm when measured after 9 months or 10 months, more preferably after 18 or 24 months, for example wherein the amount of nitrosamines (such as N-nitroso-ribociclib in free or salt form) in the composition is no more than about 4 ppm, no more than about 3 ppm, no more than about 2 ppm, or no more than about 1 ppm when measured after 9 months or 10 months, more preferably after 18 or 24 months. Preferably, the amount of nitrosamines (such as N-nitroso-ribociclib in free or salt form) in the composition is no more than about 1 ppm when measured after 9 months or 10 months, more preferably after 18 or 24 months. In some aspects, the amount of nitrosamines (such as N-nitroso-ribociclib in free or salt form) in the composition is no more than about 0.9 ppm, no more than about 0.8 ppm, no more than about 0.7 ppm, no more than about 0.6 ppm, no more than about 0.5 ppm, no more than about 0.4 ppm, no more than about 0.3 ppm, no more than about 0.2 ppm, no more than about 0.1 ppm, no more than about 0.05 ppm, or no more than about 0.025 ppm when measured after 9 or 10 months, more preferably after 18 or 24 months. In a preferred aspect, the amount of nitrosamines (such as N-nitroso-ribociclib in free or salt form) in the composition is no more than about 0.7 ppm, for example no more than about 0.6 ppm, when measured after PAT059729-WO-PCT03 85 9 or 10 months, more preferably after 18 or 24 months. For example, the measurement may be taken 9 months or 10 months, more preferably 18 months or 24 months, after the date of release of the composition. The invention also provides a composition comprising ribociclib or a pharmaceutically acceptable salt thereof, wherein the amount of nitrosamines (such as N-nitroso-ribociclib in free or salt form) in the composition when measured after 9 months or 10 months, more preferably after 18 or 24 months, is no more than an amount which would result in an amount of said nitrosamines (such as N-nitroso-ribociclib in free or salt form) that corresponds to an amount of 400 ng / day of nitrosamine free base (such as N-nitroso-ribociclib free base) being administered to the patient when the composition is administered according to an approved dosage regimen of ribociclib or pharmaceutically acceptable salt thereof. For example, the measurement may be taken 9 months or 10 months, more preferably 18 months or 24 months, after the date of release of the composition. The invention also provides a composition comprising ribociclib or a pharmaceutically acceptable salt thereof, wherein the total amount of N-nitroso-ribociclib in free or salt form in the composition is no more than about 5 ppm, relative to the total amount of ribociclib in free or salt form, when measured after 9 months or 10 months, more preferably after 18 or 24 months, for example wherein the total amount of N-nitroso-ribociclib in free or salt form in the composition is no more than about 4 ppm, no more than about 3 ppm, no more than about 2 ppm, or no more than about 1 ppm, relative to the total amount of ribociclib in free or salt form, when measured after 9 months or 10 months, more preferably after 18 or 24 months. Preferably, the total amount of N-nitroso- ribociclib in free or salt form in the composition is no more than about 1 ppm, relative to the total amount of ribociclib in free or salt form, when measured after 9 months or 10 months, more preferably after 18 or 24 months. In some aspects, the total amount of N-nitroso-ribociclib in free or salt form in the composition is no more than about 0.9 ppm, no more than about 0.8 ppm, no more than about 0.7 ppm, no more than about 0.6 ppm, no more than about 0.5 ppm, no more than about 0.4 ppm, no more than about 0.3 ppm, no more than 0.2 ppm, no more than about 0.1 ppm, no more than about 0.05 ppm, or no more than about 0.025 ppm, relative to the total amount of ribociclib in free or salt form, when measured after 9 months or 10 months, more preferably after 18 or 24 months. In a preferred aspect, the total amount of N-nitroso-ribociclib in free or salt form in the composition is no more than about 0.7 ppm, for example no more than about 0.6 ppm, relative to the total amount of ribociclib in free or salt form, when measured after 9 months or 10 months, more preferably after 18 or 24 months. For example, the measurement may be taken 9 months or 10 months, more preferably 18 months or 24 months, after the date of release of the composition. The invention also provides a composition comprising ribociclib or a pharmaceutically acceptable salt thereof, wherein the amount of N-nitroso-ribociclib in free or salt form in the composition when measured after 9 months or 10 months, more preferably after 18 or 24 months, is no more than an amount which would result in an amount of said N-nitroso-ribociclib in free or salt form that corresponds to an amount of 400 ng / day of N- nitroso-ribociclib free base being administered to the patient when the composition is administered according to an approved dosage regimen of ribociclib or pharmaceutically acceptable salt thereof. For example, the PAT059729-WO-PCT03 measurement may be taken 9 months or 10 months, more preferably 18 months or 24 months, after the date of release of the composition. The invention also provides a composition comprising ribociclib or a pharmaceutically acceptable salt thereof, wherein the amount of total nitrosamines, including both N-nitroso-ribociclib in free or salt form and other nitrosamines, in the composition is no more than about 5 ppm when measured after 9 months or 10 months, more preferably after 18 or 24 months, for example wherein the total amount of the amount of total nitrosamines, including both N-nitroso-ribociclib in free or salt form and other nitrosamines, in the composition is no more than about 4 ppm, no more than about 3 ppm, no more than about 2 ppm, or no more than about 1 ppm when measured after 9 months or 10 months, more preferably after 18 or 24 months. Preferably, the amount of total nitrosamines, including both N-nitroso-ribociclib in free or salt form and other nitrosamines, in the composition is no more than about 1 ppm when measured after 9 months or 10 months, more preferably after 18 or 24 months. In some aspects, the amount of total nitrosamines, including both N-nitroso-ribociclib in free or salt form and other nitrosamines, in the composition is no more than about 0.9 ppm, no more than about 0.8 ppm, no more than about 0.7 ppm, no more than about 0.6 ppm, no more than about 0.5 ppm, no more than about 0.4 ppm, no more than about 0.3 ppm, no more than about 0.2 ppm, no more than about 0.1 ppm, no more than about 0.05 ppm, or no more than about 0.025 ppm when measured after 9 months or 10 months, more preferably after 18 or 24 months. In a preferred aspect, the amount of total nitrosamines, including both N-nitroso-ribociclib in free or salt form and other nitrosamines, in the composition is no more than about 0.7 ppm, for example no more than about 0.6 ppm, when measured after 9 months or 10 months, more preferably after 18 or 24 months. For example, the measurement may be taken 9 months or 10 months, more preferably 18 months or 24 months, after the date of release of the composition. The invention also provides a composition comprising ribociclib or a pharmaceutically acceptable salt thereof, wherein the amount of total nitrosamines, including both N-nitroso-ribociclib in free or salt form and other nitrosamines, in the composition, when measured after 9 months or 10 months, more preferably after 18 or 24 months, is no more than an amount which would result in an amount of said total nitrosamines that corresponds to an amount of 400 ng / day of total nitrosamine free base being administered to the patient when the composition is administered according to an approved dosage regimen of ribociclib or pharmaceutically acceptable salt thereof. For example, the measurement may be taken 9 months or 10 months, more preferably 18 months or 24 months, after the date of release of the composition. The start of shelf life may be determined in accordance with EU guidance CPMP / QWP / 072 / 96 (transmitted to CPMP in June 1996 and coming into operation in December 2001), e.g., it is no later than the date on which the ribociclib or pharmaceutically acceptable salt thereof is first combined with an excipient. In particular, for a composition comprising ribociclib or a pharmaceutically acceptable salt thereof, the date of production of the composition may be taken as the date that the first step is performed involving combining the ribociclib or pharmaceutically acceptable salt thereof with other ingredients. For a composition consisting of ribociclib or a PAT059729-WO-PCT03 87 pharmaceutically acceptable salt thereof, the date of production of the composition may be taken as the date on which the ribociclib or pharmaceutically acceptable salt thereof is filled into a container for use as a medicinal product. The date of release of the composition may be taken as the start of shelf life. However, if the composition is released later than 30 days from the date of production, then the date of production, rather than the date of release, may be taken as the start of the shelf life. Manufacture of N-nitroso-ribociclib The invention further provides a method of producing N-nitroso-ribociclib or a salt thereof, wherein the method comprises reacting ribociclib or a salt thereof with nitrous acid or a derivative thereof so as to produce said compound. The derivative of nitrous acid may be a nitrite, for example sodium nitrite. The invention also provides a method of manufacturing a solution for use as a reference standard in a method of detecting an impurity in a composition comprising ribociclib or a pharmaceutically acceptable salt thereof. Preferably, the impurity is N-nitroso-ribociclib or a salt thereof. The method may comprise the steps of: (a) obtaining an amount of N-nitroso-ribociclib or a salt thereof; and (b) dissolving the N-nitroso-ribociclib or salt thereof in an amount of a solvent, thereby to produce a solution of said N-nitroso-ribociclib or salt thereof at a predetermined concentration. The method may further comprise the step of (c) diluting the solution in the solvent to provide one or more further solutions having different predetermined concentrations of said N-nitroso-ribociclib or salt thereof. A further aspect of the invention is a set of solutions comprising N-nitroso-ribociclib or a salt thereof at different concentrations. Compositions with reduced concentration of nitrites The invention further provides a composition comprising or consisting of ribociclib or a pharmaceutically acceptable salt thereof, wherein said composition is substantially free of nitrites. The total amount of nitrites in the composition may be no more than 5 ppm, for example no more than about 4 ppm, no more than about 3 ppm, no more than about 2 ppm, no more than about 1 ppm, no more than about 0.5 ppm, no more than about 0.4 ppm, no more than about 0.3 ppm, no more than about 0.25 ppm, or no more than about 0.2 ppm. Preferably, the total amount of nitrites in the composition is no more than 1 ppm. When crospovidone is used as an excipient in the composition, preferably, the nitrite contributed by the crospovidone is less than 0.1 ppm. When microcrystalline cellulose is used as an excipient in the composition, preferably, the nitrite contributed by the microcrystalline cellulose is less than 0.1 ppm. Thus, an aspect of the invention relates to a composition comprising or consisting of ribociclib or a pharmaceutically acceptable salt thereof, wherein the total amount of nitrites in the composition is no more than 1 ppm. For example, the total amount of nitrites in the composition may be no more than about 0.9 ppm, no more than about 0.8 ppm, no more than about 0.7 ppm, no more than about 0.6 ppm, no more than about 0.5 ppm, no more than about 0.4 ppm, no more than about 0.3 ppm, no more than about 0.2 ppm, no more than about 0.1 ppm, no more than about 0.05 PAT059729-WO-PCT03 88 ppm, or no more than about 0.025 ppm. Preferably, the total amount of nitrites in the composition may be no more than about 0.7 ppm, for example no more than about 0.6 ppm. The composition of ribociclib or a pharmaceutically acceptable salt thereof may be in the form of a solution. For example, the composition may be a solution of ribociclib or a pharmaceutically acceptable salt thereof in a solvent. The solvent may be or comprise isopropanol, n-propanol, methyl tert-butyl ether, ethyl acetate, isopropyl acetate, or ethanol. In some aspects, the solvent may be isopropanol. Alternatively, the one or more solvents may not be or may not comprise isopropanol. The solvent may comprise isopropanol and water, for example it may be or may comprise a solvent mixture of isopropanol and water with at least 10%, at least 20 vol%, at least 30 vol%, at least 40 vol%, at least 50 vol%, at least 60 vol%, and preferably at least 70 vol% isopropanol. The composition of the invention may be administered in the form of a tablet. Examples of suitable tablets and suitable methods for making the tablets are provided in WO 2016 / 166703 and in U.S. Patent No.10,799,506 which are incorporated by reference in their entirety. In particular, Example 3 of U.S. Patent No.10,799,506 describes coated tablets, and this example is incorporated by reference. The tablets may be coated with an immediate release coating material. Coating materials such as Opadry®, Opadry® 200, Opadry® amb II. Opadry®, Opadry® 200, Opadry® amb II, Opadry® fx™, Opadry® II, and Opalux® are all commercially available through Colorcon, Inc. Coating materials such as Opadry White, Opadry Red and Opadry Black are likewise all commercially available through Colorcon, Inc. In some embodiments in which the composition of the invention is in the form of a coated tablet, the tablet coating may comprise or consist of iron oxide black (E172), iron oxide red (E172), soya lecithin (E322), polyvinyl alcohol (partially hydrolysed), talc, titanium dioxide (E171), and / or xanthan gum. In some embodiments in which the composition of the invention is in the form of a coated tablet, the tablet coating may comprise or consist of about 0.5 wt% iron oxide black (E172), about 0.3 wt% iron oxide red (E172), about 2.0 wt% soya lecithin (E322), about 45.5 wt% polyvinyl alcohol (partially hydrolysed), about 20.0 wt% talc, about 31.3 wt% titanium dioxide (E171), and about 0.5 wt% xanthan gum, wherein the wt% are each defined relative to the weight of the tablet coating. Preferably, the tablet coating comprises or consists of about 0.47 wt% iron oxide black (E172), about 0.27 wt% iron oxide red (E172), about 2.00 wt% soya lecithin (E322), about 45.51 wt% polyvinyl alcohol (partially hydrolysed), about 20.00 wt% talc, about 31.26 wt% titanium dioxide (E171), and about 0.48 wt% xanthan gum, wherein the wt% are each defined relative to the weight of the tablet coating. In some embodiments in which the composition of the invention is in the form of a 200 mg ribociclib tablet which is a coated tablet, the tablet coating may comprise or consist of about 0.1 mg iron oxide black (E172), about 0.05 mg iron oxide red (E172), about 0.3 mg soya lecithin (E322), about 7.8 mg polyvinyl alcohol (partially hydrolysed), about 3.4 mg talc, about 5.4 mg titanium dioxide (E171), and about 0.1 mg xanthan gum. In some embodiments in which the composition of the invention is in the form of a 200 mg PAT059729-WO-PCT03 89 ribociclib tablet which is a coated tablet, the tablet coating may comprise or consist of about 0.08 mg iron oxide black (E172), about 0.05 mg iron oxide red (E172), about 0.34 mg soya lecithin (E322), about 7.83 mg polyvinyl alcohol (partially hydrolysed), about 3.44 mg talc, about 5.38 mg titanium dioxide (E171), and about 0.08 mg xanthan gum. In some embodiments in which the composition of the invention is in the form of a coated tablet, the total coating weight may be from about 1% to about 6%, preferably from about 2% to about 5%, more preferably from about 3% to about 4%, even more preferably from about 3.75% to about 3.95%, and most preferably about 3.84% by weight of the total coated tablet weight. In some embodiments in which the composition of the invention is in the form of a 200 mg ribociclib tablet which is a coated tablet, the total coated tablet weight may be about 447.20 mg and the total coating weight may be from about 15 mg to about 20 mg, preferably about 17.20 mg. In some embodiments in which the composition of the invention is in the form of a 200 mg ribociclib tablet which is a coated tablet, the tablet coating may comprise or consist of the following premix ingredients: Ingredient Quantity (mg) per 200 mg ribociclib tablet Basic coating premix white Polyvinyl alcohol (partially hydrolysed) 7.649 Titanium dioxide (E171) 5.377 Talc 3.361 Lecithin (soya) (E322) 0.336 Xanthan gum 0.081 Basic coating premix black Polyvinyl alcohol (partially hydrolysed) 0.113 Iron oxide black (E172) / ferrosoferric 0.080 oxide Talc 0.050 Lecithin (soya) (E322) 0.005 Xanthan gum 0.001 Basic coating premix red PAT059729-WO-PCT03 90 Polyvinyl alcohol (partially hydrolysed) 0.066 Iron oxide red (E172) 0.047 Talc 0.029Lecithin (soya) (E322) 0.003 Xanthan gum 0.001 The content of nitrites in the or each coating material, or in the coating as a whole, may be no more than about 2 ppm, no more than about 1 ppm, no more than about 0.5 ppm, no more than about 0.2 ppm, or no more than about 0.1 ppm. Palbociclib embodiments Another CDK4 / 6 inhibitor that has a similar structure to ribociclib and which is likewise used in the treatment of breast cancer is palbociclib. Palbociclib also contains a piperazine ring that is a potential target for nitrosamine formation. Thus, the findings presented herein in relation to ribociclib are expected to be applicable mutatis mutandis to palbociclib. As such, the disclosure herein of aspects, embodiments, clauses, claims and statements of invention that are presented in relation to ribociclib give rise to corresponding aspects, embodiments, clauses, claims and statements of invention in which ribociclib and N-nitroso-ribociclib are substituted for palbociclib and N-nitroso-palbociclib, respectively. Such aspects, embodiments, clauses, claims and statements of invention relating to palbociclib are within the scope of the present disclosure, including the present invention.

[0003] PAT059729-WO-PCT03 EXAMPLES The present examples summarize the investigations that were performed by the present inventors in order to identify the root cause of the formation of N-nitroso-ribociclib (“DMP433”) in the commercial process for manufacturing ribociclib succinate. The examples also describe the development and evaluation of measures that were aimed at minimizing the formation and content of nitrosamines, and in particular N- nitroso-ribociclib in free or salt form, in a preparation comprising ribociclib or a pharmaceutically acceptable salt thereof, such as a preparation of ribociclib succinate. Example 1 – Manufacturing Process The synthetic route and the manufacturing process for the synthesis of ribociclib succinate from the starting materials are presented below:

[0004] PAT059729-WO-PCT03

[0005] PAT059729-WO-PCT03

[0006] PAT059729-WO-PCT03 For the formation of the nitrosamine drug substance-related impurity (NDSRI) DMP433, besides the free secondary amine, a nitrite source is thought to be required. For this reason, the final two chemical steps in the above scheme, starting from compound B9, were the focus of an investigation: after cleavage of the Boc protecting group, a vulnerable secondary amine is generated. An examination of the synthesis scheme revealed no obvious source of nitrite. Example 2 – Root cause investigation The investigation into the root cause of the production of DMP433 focused on an evaluation of the manufacturing equipment, as well as the reagents, solvents and intermediates used in the final two manufacturing steps. In particular, their potential to cause the formation of DMP433 was examined. Manufacturing equipment For the manufacturing of ribociclib succinate, standard manufacturing equipment is used. In the salt formation step B10 to B12, one active carbon filter as well as two polishing filters are used. These filters were evaluated for the presence of nitrite. PAT059729-WO-PCT03 Carbon filter: The carbon filter in step B12 is used to remove any residual Pd. Pd is used in step B3 and to avoid a coloration of the isolated drug substance, ribociclib succinate. The carbon filter material was tested for the presence of nitrite. In all investigated samples, the amount of nitrite found was found to be < 1ppm. Additional experiments were performed in which the reaction from B10 to B12 was performed using different carbon filter parts, and the formation of DMP433 was monitored (two different carbon filterers from Pall and 3M were tested; Experiments “LEE011-cusakal1-050” and “LEE011-cusakal1-048”). In parallel, a control experiment without the use of carbon filter parts was also performed (Experiment “LEE011-cusakal1-049”). Since there was no significant difference between the amounts of DMP433 formed in the control experiment and in the experiments with the carbon filters, it was concluded that carbon filters do not contribute significantly to the formation of DMP433. Conclusion: due to the very low amount of nitrite on the active carbon filter, the filter is not regarded as a significant contributor to DMP433 formation. The investigated filters (3M, Pall) and the results of the testing for the presence of nitrites are presented in the following table: Nitrite found in active carbon filter Sample - batch No.Content of Nitrite inActivated carbon filter Production site22162A061 (3M) < 1 ppm Raybow 922160A012(Pall) < 1 ppm Raybow 922162A046(3M) < 1 ppm Raybow 2-ABD / 018 < 1 ppm Mengeš Polishing filter: Different types of polishing filters are used in the commercial manufacturing process. It was evaluated if there is a correlation between the type of polishing filter used and the amount of DMP433 that is found in the drug substance (“DS”). The results are presented in the following table: DMP433 found when different polishing filters are used Description Batch No. Vendor DMP433 (ppm) 1st pre.val.batch B692472 Hangzhou Cobetter Filtration 0,364 1st.val.batch B695104 EMD Millipore Corporation 76,702 2nd.val.batch B695105 EMD Millipore Corporation 71,498 3rd.val.batch B695106 Hangzhou Cobetter Filtration 0,811 PAT059729-WO-PCT03 96 5th post val. Batch B696587 Hangzhou Cobetter Filtration 0,383 6th post val. Batch B696588 Hangzhou Cobetter Filtration 0,537 7th post val. Batch B696589 Hangzhou Cobetter Filtration 0,363 8th post val. Batch B696590 EMD Millipore Corporation 58,916 9th post val. Batch B698293 EMD Millipore Corporation 59,598 10th post val. Batch B698294 EMD Millipore Corporation 95,528 11th post val. Batch B698295 EMD Millipore Corporation 86,595 12th post val. Batch B698296 EMD Millipore Corporation 87,001 13th post val. Batch B698297 Hangzhou Cobetter Filtration 1,211 14th post val. Batch B698298 Pall Ilfracombe 0,694 15th post val. Batch B699003 Pall Ilfracombe 0,705 A clear correlation between use of the EMD Millipore filter and high levels of DMP433 in the B12 step were observed. In the laboratory, tests were performed to confirm these high DMP433 values: individual parts of the dismantled filter including the housing, the membrane and the O-ring were added to the reaction mixture. A clear correlation between the filter membrane and the formation of DMP433 was demonstrated. Results of the laboratory use tests are shown in the following table: DMP433 found when testing parts of the EMD Millipore filter No. Experiments DMP433 [ppm] Nitrite [ppm] Comment LEE-B10 1 LEE011- 3949,394 app.1,24 w. Millipore filter Batch: cusakal1-019 (AS&T LJ LC-MS / MS) (QLS LJ LC-FLD / DAN) (Mengeš) B685591* I32942112W 2 LEE011- 2,105 LJ app.0,40 ppm Control experiment cusakal1-020 (AS&T LJ LC-MS / MS) (QLS LJ LC-FLD / DAN) I32942212W 3 LEE011- 1,682 LJ app.0,26 ppm w. Cobetter filter cusakal1-021 (AS&T LJ LC-MS / MS) (QLS LJ LC-FLD / DAN) (Mengeš) I32943312W 4 LEE011- 1,687 LJ app.0,32 ppm Control experiment cusakal1-022 (AS&T LJ LC-MS / MS) (QLS LJ LC-FLD / DAN) I32943412W 5 LEE011- 2,823 app.0,3 ppm w. Pall Fluorodyne II cusakal1-030 (AS&T LJ LC-MS / MS) (QLS LJ LC-FLD / DAN) filter (Mengeš) I72904501A 6 LEE011- 1,755 app.0,3 ppm w.3M Betafine filter cusakal1-031 (AS&T LJ LC-MS / MS) (QLS LJ LC-FLD / DAN) cartridge (Raybow) I72904601A 7 LEE011- 1,487 app.0,3 ppm w. Amazon Filter cusakal1-032 (AS&T LJ LC-MS / MS) (QLS LJ LC-FLD / DAN) (Raybow) I72904701A 8 LEE011- 1,272 app.0,3 ppm w.3M Life ASSURE cusakal1-033 (AS&T LJ LC-MS / MS) (QLS LJ LC-FLD / DAN) PFS Series Filter I72904801A Cartridge, Lot: M33316-002 (Raybow) 9 LEE011- 1,789 app.0,2 ppm w.3M LifeASSURE Batch: cusakal1-034 (AS&T LJ LC-MS / MS) (QLS LJ LC-FLD / DAN) PFS Series Filter B705468** I72903401A Cartridge, Lot: M28621004 (Raybow) 10 LEE011- 1,661 app.0,2 ppm Control experiment cusakal1-035 (AS&T LJ LC-MS / MS) (QLS LJ LC-FLD / DAN) I72903501A 11 LEE011- 2,100 app.0,3 ppm w. Advanced cusakal1-036 (AS&T LJ LC-MS / MS) (QLS LJ LC-FLD / DAN) Microdevices PVT. Ltd. I72903601A (Divis) PAT059729-WO-PCT03 97 12 LEE011- 1,932 app.0,3 ppm w. Divi´s Laboratories cusakal1-037 (AS&T LJ LC-MS / MS) (QLS LJ LC-FLD / DAN) Ltd. Membrane multi I72903701A filament Defender (Divis) 13 LEE011- 0,876 app.0,2 ppm w.3M carbon filter Batch: cusakal1-048 (AS&T LJ LC-MS / MS) (QLS LJ LC-FLD / DAN) (Mengeš) B705468** I72908502A 14 LEE011- 0,530 app.0,6 ppm w. Pall carbon filter cusakan1-050 (AS&T LJ LC-MS / MS) (QLS LJ LC-FLD / DAN) (Supradisc) (Mengeš) I72909402A 15 LEE011- 0,399 app.0,4 ppm Control experiment cusakan1-049 (AS&T LJ LC-MS / MS) (QLS LJ LC-FLD / DAN) I72908602A *LEE011-B10 SM (B685591): DMP4330,008 ppm; nitrite 1,4 ppm. **LEE011-B10 SM (B705468): DMP4330,03 ppm; nitrite < 0,1 ppm. Upon request, EMD Millipore confirmed that their filter membrane contains nitrocellulose, which is a significant nitrite source in the process. The Hangzhou Cobetter filter Pall Ilfracombe, 3M and Amazon filters were also investigated, but did not show an impact on the amount of DMP433 that is formed in the process. Conclusion: the EMD Millipore filter has been identified as a significant source of nitrite, which in combination with LEE011 B10 results in the formation of high amounts of DMP433. The stainless steel 316L (SS316L) filter was tested at two sites. It was confirmed in both experiments that no corrosion occurred (no metal ions in the sample) when succinic acid was contacted with the stainless steel. Thus, it was confirmed that there was no metal release with the metal filter construction. Raw materials used in the synthesis of ribociclib succinate Manufacturing of Ribocliclib free base (LEE011 B10) The Boc protecting group is cleaved under acidic conditions by HCl. In cases where nitrite is present, the reaction conditions would be optimal to form the NDSRI DMP433. Potassium carbonate was identified as a potential source of nitrite. Potassium carbonate Several batches of potassium carbonate were investigated with respect to their nitrite content. The results of this investigation are provided in the following table: Nitrite content of potassium carbonate batches Vendor / User Code Nitrite (ppm) Testing site Raybow 801720A109 13 Solvias Raybow 801720A107 14 Solvias Raybow 801720A108 13 Solvias Menges 32384211 21 Solvias Menges 32504795 26 Solvias Kronox SEZ-ACG / 001 1,9 QLS Ljubljana Kronox SEZ-ACJ / 003 1,0 QLS Ljubljana PAT059729-WO-PCT03 98 Kronox DSN-ACK / 004 0,9 QLS LjubljanaKronox DSN-ACG / 003 2,5 QLS LjubljanaAndrasugar 20231220 4,6 QLS LjubljanaAndrasugar 20231219 1,8 QLS LjubljanaAndrasugar 20231218 1,7 QLS LjubljanaMenges * 32384211 24,5 QLS LjubljanaThe data show that there is a significant range of nitrite levels found in potassium carbonate. However, a major impact of the content of nitrite in potassium carbonate on the formation of DMP433 in LEE011 B10 could not be demonstrated, as shown in the following table: Nitrite content in potassium carbonate vs. DMP433 in B10 batches on commercial scale No. In use Nitrite level in Potassium Amount Nitrite DMP433 number Potassium carbonate carbonate vendor (ppm) (ppm) (ppm) in B10 1 LEE011-B10 0,6 Sinopharm ~2 g 0,5 0,09 24001 Chemical Reagent Co., Ltd 2 LEE011-B10 0,6 Sinopharm ~2 g 0,1 0,05 24002 Chemical Reagent Co., Ltd 3 LEE011-B10 23 Zhejiang Dayang ~2 g 0,1 0,05 24003 Biotech Group Co., Ltd Conclusion: potassium carbonate did not appear to be a significant contributor of nitrite into the process. Further experiments were carried out at a laboratory scale.2 x 30g experiments (with Sinopharm as the supplier of potassium carbonate), up to B10, were completed, including a 1 x 30g experiment with another supplier for comparison. The batches of potassium carbonate were investigated with respect to their nitrite content. The formation of DMP433 in LEE011 B10 was also investigated. The results of this investigation are provided in the following table: LEE011-B10 Batch Potassium carbonate source / Nitrite Nitrite DMP433 (LOQ:30 number content(ppm) (LOQ:0.1ppm) ppb) 805193A095 Dayang(801720A111) / 29.0ppm <0.1 (0.08) 55.8ppb ppm 805193A096 <0.1 (0.05)70.5ppb ppm 805193A097 <0.1(0.07)73.9ppb ppm 805193A098 Sinopharm(923048A002) / 4.8ppm <0.1(0.07) 78.8ppb ppm The data shows that the content of nitrite in potassium carbonate does not play the most important role in the formation of DMP433. Sinopharm supplied potassium carbonate with a lower amount of nitrite (4.8 ppm) compared to Raybow. The conclusions from the laboratory scale have been confirmed on a production scale. Despite the low, or no, impact of the nitrite content in potassium carbonate on the B10 quality, it is PAT059729-WO-PCT03 99 proposed to use potassium carbonate with a low nitrite content, such as the potassium carbonate from a supplier such as Sinopharm and / or Andra Sugar. Further experiments were carried out to identify potassium carbonate sources with low nitrite. Potassium carbonate from AndraSugar (4 batches), with improved sample preparation, resulted at around 1 ppm. Evonik (2x200g) were tested and the results were high. Kronox (India) samples were tested and are low on nitrites. Manufacturing of Ribociclib succinate (LEE011 B12) Due to the nature of succinic acid, the salt formation is performed under acidic conditions, so there is a possibility that any nitrite that is present in that step of the process will lead to the formation of DMP433. Ribociclib base (LEE011 B10), succinic acid (LEE011 B11) and i-propanol were investigated as potential sources of nitrite. Ribociclib base Batches of ribociclib base (LEE011 B10) were tested for the presence of nitrites by ion chromatography (LOQ app.3 ppm, LOD app.1 ppm) and of DMP433 (LOQ app.0.0625 ppm). The results are presented in the following table: Nitrite content in ribociclib base (LEE011 B10) N DMP433 [ppm] Sample Batchitrite [ppm]LOD (1 ppm)LOQ (0.0625 ppm) LEE011-B10, Raybow805193A074 < LOD < LOQ* (0.029)LEE011-B10, Raybow923037A005 < LOD < LOQ* (0.048)LEE011-B10, Raybow923037A002 < LOD < LOQ* (0.047)LEE011-B10, Raybow805193A073 < LOD < LOQ* (0.030)LEE011-B10, Raybow805193A072 < LOD < LOQ* (0.060)LEE011-B10, Raybow923037A005 < LOD < LOQ* (0.048)LEE011-B10, MengešB687416 < LOD -LEE011-B10, MengešB685591 < LOD -LEE011-B10, MengešB687418 < LOD -LEE011-B10, MengešB689736 < LOD -LEE011-B10, MengešB704193 - < LOQ* (0.006)LEE011-B10, MengešB704194 - < LOQ* (0.005)LEE011-B10, MengešB704196 - < LOQ* (0.019)LEE011-B10, MengešB705465 - < LOQ* (0.037)LEE011-B10, MengešB0705466 - < LOQ* (0.043)LEE011-B10, MengešB0705467 - < LOQ* (0.035)LEE011-B10, MengešB0705468 - < LOQ* (0.030)*All of the tested DMP433 results in ribociclib base (B10) were below LOQ < 0.0625 ppm. Results in brackets represent an extrapolation and are only an estimate of actual values. PAT059729-WO-PCT03 100 Additional batches of ribociclib base (LEE011 B10 (IP-1)) were tested for the presence of nitrites and DMP433. The results are presented in the following table: DMP433 [ppb] Nitrite [ppm] Sample Batch LOD (1 ppm) LEE011-B10 (IP-1), Raybow805193A077 51 < LODLEE011-B10 (IP-1), Raybow805193A078 78 < LODLEE011-B10 (IP-1), MengešB704193 57 < LODLEE011-B10 (IP-1), MengešB705468 130 < LODSuccinic acid Several commercial batches of succinic acid were tested for their nitrite content. In all cases only very low nitrite content was found. The results are presented...

Claims

PAT059729-WO-PCT03 Claims 1. A pharmaceutical product comprising a plurality of oral dosage forms, wherein each of the oral dosage forms is a tablet, and wherein said oral dosage forms comprise a composition comprising: (i) ribociclib or a pharmaceutically acceptable salt thereof, and (ii) one or more pharmaceutically acceptable excipients, wherein the total amount of N-nitroso-ribociclib in free or salt form in each of the oral dosage forms is no more than 1 ppm, relative to the total amount of ribociclib in free or salt form, preferably wherein the total amount of N-nitroso-ribociclib in free or salt form in each of the oral dosage forms is no more than 0.7 ppm, more preferably no more than 0.6 ppm, relative to the total amount of ribociclib in free or salt form.

2. The pharmaceutical product of claim 1, wherein the oral dosage forms are for use in the treatment of early breast cancer, preferably wherein the breast cancer is hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancer.

3. The pharmaceutical product of claim 1 or the pharmaceutical product for use of claim 2, wherein the product comprises at least 5, at least 10, at least 15, at least 20, at least 25, at least 30, at least 35, at least 40, at least 45, at least 50 or at least 60 of said oral dosage forms, such as 7, 14, 21, 28, 35, 42, 49, 56, 63 or 70 of said oral dosage forms.

4. The pharmaceutical product of any one of claims 1 or 3, or the pharmaceutical product for use of any one of claims 2 or 3, wherein each of the one or more pharmaceutically acceptable excipients has a content of nitrites of less than 0.5 ppm, less than 0.4 ppm, less than 0.3 ppm, less than 0.2 ppm, or less than 0.1 ppm, relative to the amount of the respective excipient; optionally wherein the one or more pharmaceutically acceptable excipients is more than one excipient and the combined excipients have a total content of nitrites of less than 0.5 ppm, less than 0.4 ppm, less than 0.3 ppm, less than 0.2 ppm, or less than 0.1 ppm, relative to the combined amount of the excipients.

5. The pharmaceutical product of any one of claims 1 or 3 to 4, or the pharmaceutical product for use of any one of claims 2 to 4, wherein the one or more pharmaceutically acceptable excipients are selected from the group consisting of magnesium stearate, microcrystalline cellulose, crospovidone, hydroxypropyl cellulose, and silica; optionally wherein the one or more pharmaceutically acceptable excipients comprises one or both of microcrystalline cellulose and crospovidone and (a) the content of nitrites in the microcrystalline cellulose is no more than 100 ppb and / or (b) the content of nitrites in the crospovidone is no more than 100 ppb.

6. The pharmaceutical product of any one of claims 1 or 3 to 5, or the pharmaceutical product for use of any one of claims 2 to 5, wherein each of the oral dosage forms comprises ribociclib succinate.

7. The pharmaceutical product of any one of claims 1 or 3 to 6, or the pharmaceutical product for use of any one of claims 2 to 6, wherein the total amount of ribociclib or pharmaceutically acceptable salt thereof in each of the oral dosage forms provides the same amount of ribociclib as 200 mg of ribociclib free base.PAT059729-WO-PCT03 8. The pharmaceutical product of any one of claims 1 or 3 to 7, or the pharmaceutical product for use of any one of claims 2 to 7, wherein the water activity value of each of the oral dosage forms is less than 0.08, preferably no more than 0.06, and more preferably no more than 0.

05.

9. The pharmaceutical product of any one of claims 1 or 3 to 8, or the pharmaceutical product for use of any one of claims 2 to 8, further comprising means to prevent, retard or reduce the formation of N-nitroso- ribociclib in free or salt form in the plurality of oral dosage forms; optionally wherein said means are one or any combination of the following: a. the oral dosage forms are each individually or together present in a sealed container under an atmosphere in which the percentage of oxygen is less than 21% by volume, optionally wherein the atmosphere is nitrogen; b. the oral dosage forms are each individually or together present in a sealed container which also contains a desiccant, or the oral dosage forms are together present in a sealed pharmaceutical package which also contains a desiccant in a separate container; c. the oral dosage forms each further comprise a pharmaceutically acceptable additive which prevents, retards or reduces the formation of N-nitroso-ribociclib in free or salt form, optionally wherein the pharmaceutically acceptable additive is selected from the group consisting of pH adjusters, antioxidants, radical scavenging agents, and peroxide-quenching agents.

10. The pharmaceutical product of any one of claims 1 or 3 to 9, or the pharmaceutical product for use of any one of claims 2 to 9, wherein the oral dosage forms are each individually or together present in a sealed container, optionally wherein the oral dosage forms are packaged within a blister pack such that each oral dosage form is individually packaged within a substantially moisture and / or gas impermeable blister, preferably wherein the humidity of the atmosphere within each blister is no more than 2.5 g / kg.

11. The pharmaceutical product of any one of claims 1 or 3 to 10, or the pharmaceutical product for use of any one of claims 2 to 10, wherein said oral dosage forms have a shelf life of at least 1, at least 2, at least 3, at least 4, at least 5, at least 6, at least 7, at least 8, at least 9, at least 10, at least 11, at least 12, at least 13, at least 14, at least 15, at least 16, at least 17, at least 18, at least 24, at least 30, at least 36, at least 42,at least 48, at least 54 or at least 60 months when stored at a temperature of 2 to 8 C, a temperature of 20 to25 C, a temperature of no more than 25 C, or a temperature of no more than 40 C; optionally wherein:a. said oral dosage forms have a shelf life of at least 12, at least 18, at least 24, at least 30, at least 36, at least 42, at least 48, at least 54 or at least 60 months when stored at a temperature of 2 to 8 C;and / orPAT059729-WO-PCT03 b. said oral dosage forms have a shelf life of at least 1, at least 2, at least 3, at least 4, at least 5, at least 6, at least 7, at least 8, at least 9 or at least 10 months when stored at a temperature of 20 to 25 C, preferably wherein the said oral dosage forms have a shelf life of at least 18 months, andmore preferably at least 24 months, when stored at a temperature of 20 to 25 C; and / orc. the shelf life is the period of time in which the total amount of N-nitroso-ribociclib in free or salt form in each of the oral dosage forms remains no more than 1 ppm, preferably no more than 0.7 ppm, more preferably no more than 0.6 ppm, relative to the total amount of ribociclib in free or salt form.

12. The pharmaceutical product of any one of claims 1 or 3 to 11, or the pharmaceutical product for use of any one of claims 2 to 11, wherein said pharmaceutical product comprises a document which either directly or via a link to an electronic database specifies how the pharmaceutical product should be stored, wherein if the pharmaceutical product is stored in accordance with the instructions, then the total amount of N-nitroso- ribociclib in free or salt form in each of the oral dosage forms will be no more than 1 ppm, relative to the total amount of ribociclib in free or salt form, preferably wherein the total amount of N-nitroso-ribociclib in free or salt form in each of the oral dosage forms is or will be no more than 0.7 ppm, more preferably no more than 0.6 ppm, relative to the total amount of ribociclib in free or salt form.

13. A method of storing over a period of time a composition comprising or consisting of ribociclib or a pharmaceutically acceptable salt thereof, wherein the total amount of N-nitroso-ribociclib in free or salt form in the composition at the start of the period of time is no more than a first threshold amount, and wherein the total amount of N-nitroso-ribociclib in free or salt form in the composition at the end of the period of time is no more than a second threshold amount, wherein the storing of the composition incorporates means to prevent, retard or reduce the formation of N-nitroso-ribociclib in free or salt form; optionally wherein the means to prevent, retard or reduce the formation of N-nitroso-ribociclib in free or salt form comprises or consists of one or any combination of the following: a. storing the composition in a sealed container under an atmosphere in which the percentage of oxygen is less than 21% by volume, optionally wherein the atmosphere is nitrogen; b. storing the composition in a sealed container which also contains a desiccant, or storing the composition in a sealed pharmaceutical package which also contains a desiccant in a separate container; c. storing the composition under an atmosphere in which the relative humidity is less than 75 %, optionally wherein the relative humidity is less than 60 %, and preferably wherein the relative humidity is no more than 15 %; d. storing the composition at a temperature of less than 25 C, optionally wherein the temperature is 2 to8 C;PAT059729-WO-PCT03 e. storing the composition in a sealed container under an atmosphere in which the humidity is no more than 2.5 g / kg, optionally wherein the composition is divided into a plurality of oral dosage forms that are packaged within a blister pack such that each oral dosage form is individually packaged within a substantially moisture and / or gas impermeable blister; f. incorporating in the composition one or more pharmaceutically acceptable additives which prevent, retard or reduce the formation of N-nitroso-ribociclib in free or salt form, optionally wherein each of the one or more additives is selected from the group consisting of pH adjusters, antioxidants, radical scavenging agents, and peroxide-quenching agents.

14. The method of claim 13, wherein: a. the period of time is at least 1, at least 2, at least 3, at least 4, at least 5, at least 6, at least 7, at least 8, at least 9, at least 10, at least 11, at least 12, at least 13, at least 14, at least 15, at least 16, at least 17, at least 18, at least 24, at least 30, at least 36, at least 42, at least 48, at least 54 or at least 60 months, preferably wherein the period of time is at least 12 months, more preferably wherein the period of time is at least 18 months, most preferably wherein the period of time is at least 24 months, for example at least 36 months, 48 months, or 60 months; and / or b. the first threshold amount is 0.6 ppm or 0.7 ppm, relative to the total amount of ribociclib in free or salt form and / or the second threshold amount is 1 ppm, relative to the total amount of ribociclib in free or salt form; and / or c. the composition is a pharmaceutical composition comprising one or more pharmaceutically acceptable excipients, optionally wherein the composition comprises one or both of microcrystalline cellulose and crospovidone; and / or d. the composition is an oral dosage form, optionally wherein the oral dosage form is a tablet or is part of a pharmaceutical product as defined in any one of claims 1 to 12; and / or e. the composition is part of a pharmaceutical product which further comprises one or more of: i. a document providing, either directly or via a link to an electronic database, instructions to a patient as to how to administer the composition; ii. a document providing, either directly or via a link to an electronic database, instructions which specify how the composition should be stored;PAT059729-WO-PCT03 iii. a document which, either directly or via a link to an electronic database, indicates that, provided that the composition is stored in accordance with specified instructions, the total amount of N-nitroso-ribociclib in free or salt form in the composition will be no more than the second threshold amount; and / or f. the method comprises a step of determining the total amount of N-nitroso-ribociclib in free or salt form in the composition, optionally wherein the step of determining is performed by a method which includes the Griess test and / or high performance liquid chromatography (HPLC)-mass spectroscopy and / or gas chromatography (GC)-mass spectroscopy.

15. A method of preparing ribociclib or a pharmaceutically acceptable salt thereof with an acid, wherein the method comprises the use of one or more solvents for dissolving ribociclib and / or said acid in order to obtain a solution, and wherein the method comprises one or any combination of the following: a. distilling the one or more solvents to reduce their content of nitrites, prior to said use; b. passing the one or more solvents through an ion exchange resin which is capable of adsorbing nitrites, prior to said use, preferably wherein the ion exchange resin is selected from the group consisting of an activated charcoal resin, a silica gel resin, a celite resin, or an aluminium oxide resin; c. filtering the or each solution obtained with a filter that does not comprise a nitrocellulose membrane, preferably wherein the or each filter is a metal filter or a stainless steel filter, optionally wherein the mesh size of the filter is 0.5 m; optionally wherein the method comprises: (a) distilling the one or more solvents to reduce their content of nitrites; and (b) passing the one or more distilled solvents through an ion exchange resin which is capable of adsorbing nitrites.

16. The method of claim 15, wherein the method comprises: (a) obtaining one or more solvents, optionally wherein the one or more solvents are contained in a sealed container under an atmosphere in which the percentage of oxygen is less than 21% by volume, preferably wherein the atmosphere is nitrogen; (b) distilling the one or more solvents to reduce their content of nitrites; and (c) using the one or more distilled solvents to dissolve ribociclib and / or said acid.

17. The method of claim 15 or claim 16, wherein: a. at least one or each of the one or more solvents is or comprises isopropanol, optionally wherein the distillation of the isopropanol is over ascorbic acid; and / orPAT059729-WO-PCT03 b. the total amount of nitrites in each of the one or more solvents, following the distillation, is no more than 5 ppb, preferably no more than 3.5 ppb, and more preferably no more than 1 ppb, relative to the amount of the respective solvent, optionally wherein the one or more solvents is more than one solvent and the combined total amount of nitrites in the solvents is no more than 5 ppb, preferably no more than 3.5 ppb, and more preferably no more than 1 ppb, relative to the combined amount of the solvents; and / or c. at least one or each of the one or more solvents is or comprises isopropanol and the isopropanol is or becomes substantially free of isopropyl nitrite.

18. A method of preparing the pharmaceutical product of any one of claims 1 to 12, wherein the method comprises one or any combination of the following: a. sealing the oral dosage forms individually or together in a container under an atmosphere in which the percentage of oxygen is less than 21% by volume, optionally wherein the atmosphere is nitrogen; b. sealing the oral dosage forms individually or together in a container which also contains a desiccant, or sealing the oral dosage forms together in a pharmaceutical package which also contains a desiccant in a separate container; c. incorporating in each of the oral dosage forms one or more pharmaceutically acceptable additives which prevent, retard or reduce the formation of N-nitroso-ribociclib in free or salt form, optionally wherein each of the one or more additives is selected from the group consisting of pH adjusters, antioxidants, radical scavenging agents, and peroxide-quenching agents; d. sealing the oral dosage forms individually or together in a container under an atmosphere in which the humidity is no more than 2.5 g / kg, optionally wherein the method comprises sealing the oral dosage forms within a blister pack such that each oral dosage form is individually sealed within a substantially moisture and / or gas impermeable blister.

19. Use of a reagent and / or an intermediate to prepare ribociclib or a pharmaceutically acceptable salt thereof, wherein: a. the reagent is potassium carbonate, and the amount of nitrites in the potassium carbonate is no more than 5 ppm; and / or b. the intermediate is ribociclib free base, and the amount of nitrites in the ribociclib free base is no more than 5 ppm; and / orPAT059729-WO-PCT03 c. the reagent is an organic or inorganic acid, and the amount of nitrites in the organic or inorganic acid is no more than 5 ppm, optionally wherein the reagent is succinic acid; and / or d. the reagent is one or more solvents, and the total amount of nitrites in each of the one or more solvents is no more than about 5 ppb, optionally wherein the one or more solvents is or comprises isopropanol and / or optionally wherein the one or more solvents are distilled.

20. Use of one or more pharmaceutically acceptable excipients to prepare a pharmaceutical composition comprising: (i) ribociclib or a pharmaceutically acceptable salt thereof; and (ii) one or more pharmaceutically acceptable excipients, wherein: a. the one or more pharmaceutically acceptable excipients is or comprises magnesium stearate, and the content of nitrites in the magnesium stearate is no more than 5 ppm; and / or b. the one or more pharmaceutically acceptable excipients is or comprises microcrystalline cellulose, and the content of nitrites in the microcrystalline cellulose is no more than 100 ppb; and / or c. the one or more pharmaceutically acceptable excipients is or comprises crospovidone, and the content of nitrites in the crospovidone is less than 100 ppb; and / or d. the one or more pharmaceutically acceptable excipients is or comprises hydroxypropyl cellulose, and the content of nitrites in the hydroxypropyl cellulose is no more than 500 ppb; and / or e. the one or more pharmaceutically acceptable excipients is or comprises silica, and the content of nitrites in the silica is no more than 500 ppb.

21. Use of a desiccant for preventing, retarding or reducing the formation of N-nitroso-ribociclib in free or salt form in a composition comprising or consisting of ribociclib or a pharmaceutically acceptable salt thereof, wherein the use comprises storing the composition in the presence of the desiccant.

22. A process for preparing a pharmaceutical product comprising a composition that comprises: (i) ribociclib or a pharmaceutically acceptable salt thereof; and (ii) one or more pharmaceutically acceptable excipients, the process comprising: a. obtaining a batch of ribociclib or of a pharmaceutically acceptable salt thereof; b. determining the total amount of N-nitroso-ribociclib in free or salt form in a sample of said batch; andPAT059729-WO-PCT03 c. preparing the pharmaceutical product from the batch only if the sample of the batch is determined to have a total amount of N-nitroso-ribociclib in free or salt form of no more than 1 ppm, preferably no more than 0.7 ppm, more preferably no more than 0.6 ppm, relative to the total amount of ribociclib in free or salt form, optionally wherein the pharmaceutical product is a pharmaceutical product as defined in any one of claims 1 to 12, and / or optionally wherein the step of determining the total amount of N-nitroso-ribociclib in free or salt form is performed by a method which includes the Griess test and / or high performance liquid chromatography (HPLC)-mass spectroscopy and / or gas chromatography (GC)-mass spectroscopy.

23. A process for preparing a pharmaceutical product comprising a composition that comprises: (i) ribociclib or a pharmaceutically acceptable salt thereof; and (ii) one or more pharmaceutically acceptable excipients, the process comprising: a. preparing a first batch of a composition comprising or consisting of ribociclib or a pharmaceutically acceptable salt thereof; b. determining the total amount of N-nitroso-ribociclib in free or salt form in a sample of said first batch; c. discarding the first batch if the first batch is determined to have a total amount of N-nitroso- ribociclib in free or salt form of more than 1 ppm, preferably more than 0.7 ppm, more preferably more than 0.6 ppm, relative to the total amount of ribociclib in free or salt form; and d. preparing a second batch of a composition comprising or consisting of ribociclib or a pharmaceutically acceptable salt thereof; wherein the reagents and / or conditions that are used in step d are adjusted relative to the reagents and / or conditions that are used in step a so as to prevent, retard or reduce the formation of N-nitroso-ribociclib in free or salt form, and optionally wherein the step of determining the total amount of N-nitroso-ribociclib in free or salt form is performed by a method which includes the Griess test and / or high performance liquid chromatography (HPLC)-mass spectroscopy and / or gas chromatography (GC)-mass spectroscopy.

24. The process of claim 23, wherein the reagents and / or conditions that are adjusted in the process include any one or any combination of the following: a. the ribociclib or pharmaceutically acceptable salt thereof, optionally wherein the pharmaceutically acceptable salt is ribociclib succinate; b. the one or more pharmaceutically acceptable excipients, optionally wherein the one or more pharmaceutically acceptable excipients are selected from the group consisting of magnesium stearate, microcrystalline cellulose, crospovidone, hydroxypropyl cellulose, and silica; andPAT059729-WO-PCT03 c. one or more solvents that are used in preparing the composition, optionally wherein the one or more solvents is or comprises isopropanol.

25. A method of preparing a pharmaceutical product comprising a plurality of oral dosage forms, wherein each of the oral dosage forms is a tablet, and wherein said oral dosage forms comprise a composition comprising: (i) ribociclib or a pharmaceutically acceptable salt thereof; and (ii) one or more pharmaceutically acceptable excipients, wherein the method comprises: (a) providing the composition; (b) compressing the composition into tablets; (c) applying a film coating to the tablets; and (d) drying the tablets until the water activity value of the tablets is less than 0.08, preferably no more than 0.06, and more preferably no more than 0.05.

26. The method of claim 25, wherein the step of drying the tablets is conducted at a temperature of 25 Cto 50 C, preferably at a temperature of 28 C to 32 C, and more preferably at a temperature of about 30 C,optionally wherein the step of drying the tablets is conducted at the said temperature for a time period of at least 44 hours, at least 48 hours, at least 52 hours, at least 56 hours, at least 60 hours, at least 64 hours, at least 68 hours, or at least 72 hours, preferably wherein the step of drying the tablets is conducted at the said temperature for a time period of at least 56 hours.

27. The method of claim 25 or 26, wherein the step of drying the tablets is conducted by flowing an atmosphere over the tablets, wherein the humidity of the atmosphere is no more than 0.5 g / kg, preferably no more than 0.1 g / kg, and more preferably no more than 0.01 g / kg, optionally wherein the flow rate of the atmosphere is 28 to 30 m3 / h.

28. The method of claim 27, wherein the atmosphere is air, optionally wherein prior to being flowed over the tablets, the air is treated to reduce its content of NOx species.

29. The method of any one of claims 25 to 28, wherein both before and after the step of drying the tablets, the total amount of N-nitroso-ribociclib in free or salt form in each of the tablets is no more than 0.7 ppm, and preferably no more than 0.6 ppm, relative to the total amount of ribociclib in free or salt form.

30. The method of any one of claims 25 to 29, wherein the pharmaceutical product is a pharmaceutical product as defined in any one of claims 1 to 12.

31. A tablet comprising (i) ribociclib or a pharmaceutically acceptable salt thereof; and (ii) one or more pharmaceutically acceptable excipients, wherein: (1) the total amount of nitrosamines in the tablet, or at least the total amount of N-nitroso-ribociclib in free or salt form in the tablet, is no more than 1 ppm, preferably no more than 0.7 ppm, and more preferably no more than 0.6 ppm, relative to the total amount of ribociclib in free or salt form; (2) the tablet has a water activity value of less than 0.08, preferably no more than 0.06, and more preferably no more than 0.05; and (3) the total amount of ribociclib or pharmaceutically acceptable salt thereof in the tablet provides the same amount of ribociclib as 50 mg, 100 mg or 200 mg of ribociclib freePAT059729-WO-PCT03 base, preferably wherein the total amount of ribociclib or pharmaceutically acceptable salt thereof in the tablet provides the same amount of ribociclib as 200 mg of ribociclib free base.

32. The tablet of claim 31, wherein the tablet has a content of nitrites of no more than 5 ppm, no more than 4 ppm, no more than 3 ppm, no more than 2 ppm, no more than 1 ppm, or no more than 0.5 ppm, preferably wherein the tablet has a content of nitrites of no more than 0.4 ppm, no more than 0.3 ppm, no more than 0.2 ppm, no more than 0.1 ppm, no more than 0.05 ppm, or no more than 0.025 ppm.

33. The tablet of claim 31 or 32, wherein the combined excipients have a total content of nitrites of no more than 5 ppm, no more than 4 ppm, no more than 3 ppm, no more than 2 ppm, no more than 1 ppm, or less than 0.5 ppm, relative to the combined amount of the excipients, preferably wherein the combined excipients have a total content of nitrites of less than 0.4 ppm, less than 0.3 ppm, less than 0.2 ppm, or less than 0.1 ppm, relative to the combined amount of the excipients, and more preferably wherein the combined excipients have a total content of nitrites of less than 0.1 ppm, relative to the combined amount of the excipients.

34. The tablet of any one of claims 31 to 33, wherein the one or more pharmaceutically acceptable excipients are selected from the group consisting of magnesium stearate, microcrystalline cellulose, crospovidone, hydroxypropyl cellulose, and silica; optionally wherein the one or more pharmaceutically acceptable excipients comprises one or preferably both of microcrystalline cellulose and crospovidone and (a) the content of nitrites in the microcrystalline cellulose is no more than 100 ppb and / or (b) the content of nitrites in the crospovidone is no more than 100 ppb.

35. The tablet of claim 34, wherein the tablet comprises each of magnesium stearate, microcrystalline cellulose, crospovidone, hydroxypropyl cellulose, and silica, and wherein: (a) the content of nitrites in the microcrystalline cellulose is no more than 100 ppb; (b) the content of nitrites in the crospovidone is no more than 100 ppb; and (c) the tablet has a film coating, preferably a moisture barrier film coating.

36. The tablet of any one of claims 31 to 35, wherein the tablet is contained within a blister of a blister pack, wherein the blister is substantially moisture and / or gas impermeable, preferably wherein the blister pack is an alu-alu blister pack.

37. The tablet of any one of claims 31 to 36, wherein the tablet is for use in the treatment of early breast cancer, preferably wherein the breast cancer is hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancer.

38. A tablet comprising (i) ribociclib or a pharmaceutically acceptable salt thereof; and (ii) one or more pharmaceutically acceptable excipients, wherein the tablet has a water activity value of less than 0.08, preferably no more than 0.06, and more preferably no more than 0.05, optionally wherein the tablet has one or more of the additional requirements that are specified in claims 31 to 37.

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