Methods for assessing suitability of pharmaceutical containers for lipid-based carrier systems

Abstract

The present invention relates to a method for assessing the suitability of pharmaceutical containers for lipid-based carrier systems. Lipid-based carrier systems are sensitive pharmaceutical vehicles that require pharmaceutical containers that meet required standards for storage and transport.

Description

[Technical field]

[0001] The present invention relates to a method for assessing the suitability of pharmaceutical containers for lipid-based carrier systems. Lipid-based carrier systems are sensitive pharmaceutical vehicles that require pharmaceutical containers that meet desired criteria for storage and transportation.

[0002] background Lipid-based carrier systems, such as lipid nanoparticles (LNPs), are state-of-the-art drug delivery vehicles used for pharma- ceutical active and sensitive components, such as mRNA.

[0003] The LNPs used in the mRNA vaccine against SarS-CoV-2 are based on four chemically distinct lipids: phospholipids, cholesterol, PEG-modified lipids, and cationic lipids. Cationic lipids bind to mRNA due to their opposite molecular charge. mRNA vaccines are chemically sensitive and require high requirements for their storage conditions, e.g., temperatures well below -20°C to preserve the drug.

[0004] Therefore, high demands are placed on the container for storing and transporting mRNA vaccines.One particular problem associated with mRNA vaccines is that the adhesion of supramolecular structures to the container wall and possible inactivation have been observed.In this context, the challenge remains to evaluate pharmaceutical containers for suitability for lipid-based carrier systems in terms of storage and transport.

[0005] There are many pharmaceutical containers on the market, most of which are glass-based, but also polymer-based. Pharmaceutical containers may be coated to modify their surface properties, especially with regard to adhesion properties.

[0006] However, a method for assessing the suitability of pharmaceutical containers for lipid-based carrier systems has yet to be achieved.

[0007] Summary of the Invention In a first aspect, the present invention provides a method for assessing the suitability of a pharmaceutical container for a lipid-based carrier system, comprising the steps of: - providing a pharmaceutical container having an interior surface and an exterior surface, at least a portion of the interior surface being coated with a coating; - incubating the container with a lipid-based carrier system; - acquiring ToF-SIMS data from the interior surface of the vessel; - selecting between 10 and 1000 signals from the ToF-SIMS data; - performing a multivariate spectral resolution (MCR) analysis on selected signals from the ToF-SIMS data to obtain one or more factors; - obtaining a score corresponding to one or more factors from the MCR analysis; and - evaluating at least one score of one or more factors by comparison with a reference score; The present invention relates to a method comprising the steps of:

[0008] The method according to the invention advantageously allows to collect relevant information in the form of ToF-SIMS data from the inner surface of the container previously subjected to a typical treatment, i.e. incubation of the container with a lipid-based carrier system. The ToF-SIMS data provides a wealth of information regarding the relevant molecular (ionic) species found in the coating and / or on the container. The method advantageously allows to reduce this complex information set by MCR (multivariate spectral resolution) analysis on the ToF-SIMS data with one or more factors representative of the relevant compound classes found in the coating and / or on the container. The method provides a single score value for each chosen factor, which can be easily compared to a reference condition.

[0009] The evaluation of the score of one or more factors by comparison with a reference drug container or reference conditions makes the method versatile, i.e. an experimental reference frame suitable for the drug container can be chosen, for example a coated container can be compared with a non-coated one. Furthermore, the method allows the freedom to choose a mathematical evaluation, for example by assessing a difference or quotient value. Also, the threshold value may vary depending on a certain application and the requirements set by the authorities.

[0010] In a related aspect, the invention provides a method for evaluating the suitability of a pharmaceutical container for a lipid-based carrier system, comprising the steps of: - providing a pharmaceutical container having an interior surface and an exterior surface, at least a portion of the interior surface being coated with a coating; - incubating the container with a lipid-based carrier system; - acquiring ToF-SIMS data from the interior surface of the vessel; - selecting between 10 and 1000 signals from the ToF-SIMS data; - performing a multivariate spectral resolution (MCR) analysis on the ToF-SIMS data to obtain one or more factors; - selecting one or more factors, including lipid factor 1; - obtaining a score corresponding to lipid factor 1 from the MCR analysis; - dividing the lipid factor 1 score by the similarity score of the reference drug container to obtain a lipid factor 1 quotient; and - assessing the suitability of the pharmaceutical container for a lipid-based carrier system based on the criterion that the lipid factor 1 quotient is less than 0.67 or less than 0.5. The present invention relates to a method comprising the steps of:

[0011] In a related aspect, the invention provides a method for evaluating the suitability of a pharmaceutical container for a lipid-based carrier system, comprising the steps of: - providing a pharmaceutical container having an interior surface and an exterior surface, at least a portion of the interior surface being coated with a coating; - incubating the container with a lipid-based carrier system; - acquiring ToF-SIMS data from the interior surface of the vessel; - selecting between 10 and 1000 signals from the ToF-SIMS data; - performing a multivariate spectral resolution (MCR) analysis on the ToF-SIMS data to obtain one or more factors; - selecting one or more agents comprising a silicon-organic agent 1; - obtaining a score corresponding to silicon-organic factor 1 from the MCR analysis; - dividing the silicon-organic factor 1 score by the similarity score of the reference drug container to obtain a silicon-organic factor 1 quotient; and - evaluating the suitability of the pharmaceutical container for a lipid-based carrier system based on the criterion that the silicon-organic factor 1 quotient is greater than 2.0; The present invention relates to a method comprising the steps of:

[0012] In a related aspect, the invention provides a method for evaluating the suitability of a pharmaceutical container for a lipid-based carrier system, comprising the steps of: - providing a pharmaceutical container having an interior surface and an exterior surface, at least a portion of the interior surface being coated with a coating; - incubating the container with a lipid-based carrier system; - acquiring ToF-SIMS data from the interior surface of the vessel; - selecting between 10 and 1000 signals from the ToF-SIMS data; - performing a multivariate spectral resolution (MCR) analysis on the ToF-SIMS data to obtain one or more factors; - obtaining a score corresponding to organic factor 1 from the MCR analysis; - dividing the organic factor 1 score by the similarity score of the reference drug container to obtain an organic factor 1 quotient; and - evaluating the suitability of the pharmaceutical container for a lipid-based carrier system based on the criterion that the organic factor 1 quotient is greater than 0.2; The present invention relates to a method comprising the steps of:

[0013] Detailed Description In a first aspect, the present invention provides a method for assessing the suitability of a pharmaceutical container for a lipid-based carrier system, comprising the steps of: - providing a pharmaceutical container having an interior surface and an exterior surface, at least a portion of the interior surface being coated with a coating; - incubating the container with a lipid-based carrier system; - acquiring ToF-SIMS data from the interior surface of the vessel; - selecting between 10 and 1000 signals from the ToF-SIMS data; - performing a multivariate spectral resolution (MCR) analysis on selected signals from the ToF-SIMS data to obtain one or more factors; - obtaining a score corresponding to one or more factors from the MCR analysis; and - evaluating at least one score of one or more factors by comparison with a reference score; The present invention relates to a method comprising the steps of:

[0014] The acquired ToF-SIMS data reveals signals of numerous molecular (ionic) species originating from the container and / or coating, e.g. glass or polymer substrates, siloxanes, phospholipids, other lipids, buffer components, as well as non-specific organic molecules and inorganic salts. The high-dimensional data space created by the secondary ions, treated as individual variables, is then replaced by new variables, so-called factors. The position of a factor in the high-dimensional data space is represented by a loading. Applying MCR (multivariate spectral decomposition) analysis to the loadings on one or more of the (specific) factors results in a score.

[0015] Those skilled in the art know that ToF-SIMS provides the mass of molecular fragments detected by the instrument.Then, using analytical tools and / or suitable libraries, the obtained mass is assigned to or interpreted as a specific molecular (ion) species.Figures 5A and 5B show a list of related molecular fragments that can be assigned to a specific mass obtained by using ToF-SIMS method when applied to the pharmaceutical container of the present invention.

[0016] In an embodiment, the method comprises selecting 10-1000 signals from the ToF-SIMS data, or 20-800 signals, or 50-500 signals, or 100-200 signals. Those skilled in the art will know how to select relevant molecular (ion) species from the ToF-SIMS data depending on the vessel being investigated. In an embodiment, the method comprises selecting 10 or more signals, or 20 or more signals, or 50 or more signals, or 100 or more signals. In an embodiment, the method comprises selecting no more than 1000 signals, no more than 800 signals, no more than 500 signals, or no more than 200 signals.

[0017] In one embodiment, the method includes selecting one or more factors, e.g., 3-8 factors, 3 factors, 4 factors, 5 factors, or 3-5 factors, where the factors are selected from 1 lipid factor, 1 silicon-organic factor, 1 silicon-inorganic factor, and 1 organic factor.

[0018] In one embodiment, the pharmaceutical container is a syringe, cartridge, ampoule or glass vial, and the pharmaceutical container is a glass container or a polymeric container.

[0019] In one embodiment, the step of incubating the container with the lipid-based carrier system comprises: - filling the container with a reference composition comprising a lipid-based carrier system; - storing the filled containers; - Emptying, cleaning and drying the containers Includes.

[0020] In one embodiment of the method, - storing the filled container for at least 3 hours or at least 6 hours; - storing filled containers at a temperature below 10°C, and / or - Store filled containers at temperatures below -10°C or below -50°C.

[0021] In one embodiment of the method, before filling the container with the reference composition, the container is washed, preferably with water.

[0022] In one embodiment of the method, the reference composition comprises: - a lipid-based carrier system such as LNP, water and optionally a buffer, or - containing or being a Comirnaty® vaccine preparation (license number EU / 1 / 20 / 1528);

[0023] In one embodiment, the step of incubating the container with the lipid-based carrier system comprises: - filling the container with the reference LNP composition, freezing it to -80°C, incubating it at -80°C for 12 hours, and then thawing it to 5°C within 12 hours; or - washing the container with ultrapure water (corresponding to purity 1, DIN ISO 3696, ≦0.1 μS / cm at 25° C.), drying under laminar flow conditions, filling the container with the reference LNP composition, freezing it to −80° C., incubating it at −80° C. for 12 hours and then thawing it to 5° C. within 12 hours; Including, The reference LNP composition is the Comirnaty vaccine (license number EU / 1 / 20 / 1528), or The reference LNP composition had a saccharide content of 10% by weight and the following concentrations: [Table 1] Containing 7.2 mg / mL of (4-hydroxybutyl)azanediyl)bis(hexane-6,1-diyl)bis(2-hexyldecanoate), 0.83 mg / mL of 2[(polyethylene glycol)-2000]-N,N-ditetradecylacetamide, 1.5 mg / mL of 1,2-distearoyl-sn-glycero-3-phosphocholine, and 3.3 mg / mL of cholesterol in phosphate buffered saline (PBS) (pH 7.4).

[0024] The incubation step with the lipid-based carrier system may be different for glass and polymer vessels and is carried out under well-defined conditions to establish reproducibility and comparison of the vessels with a reference vessel.

[0025] In one embodiment, the reference LNP composition is the Comirnaty vaccine (license number EU / 1 / 20 / 1528); or In one embodiment, the reference LNP composition has a saccharide content of 10% by weight and the following concentrations: [Table 2] Containing 7.2 mg / mL of (4-hydroxybutyl)azanediyl)bis(hexane-6,1-diyl)bis(2-hexyldecanoate), 0.83 mg / mL of 2[(polyethylene glycol)-2000]-N,N-ditetradecylacetamide, 1.5 mg / mL of 1,2-distearoyl-sn-glycero-3-phosphocholine, and 3.3 mg / mL of cholesterol in phosphate buffered saline (PBS) (pH 7.4).

[0026] In one embodiment, the one or more agents further comprise a silicon-organic agent 1, a silicon-inorganic agent 1, and an organic agent 1.

[0027] In one embodiment, in performing MCR analysis on ToF-SIMS data, each factor has a factor-specific MCR loading that indicates the conceptual components in n-dimensional composition space that can be attributed to each of one or more factors, and the factor-specific MCR loading characterizes one or more factors by listing the ions / masses that contribute to the definition of said factor.

[0028] The one or more factors can be selected from lipid factor 1, silicon-organic factor 1, silicon-inorganic factor 1 and organic factor 1, each of the factors having a factor-specific MCR loading that indicates the conceptual component in the n-dimensional composition space that can be attributed to the one or more factors, and the factor-specific MCR loading characterizes the one or more factors by listing the ions that contribute to the definition of the factor.The conceptual component represents a compound class, such as lipid, siloxane and glass typical silicon species.Therefore, the conceptual component is not present in the coating or on the container.

[0029] In one embodiment, lipid factor 1 is characterized in its factor-specific MCR loading by the following ions: fatty acid ions; [C n H 2n-1 O2] - [wherein n is 10, 12, 14, 16, or 18]; [C n H 2n-3 O2] - [wherein n is 10, 12, 14, 16, or 18]; [C n H 2n-5 O2] - [where n is 16 or 18]; phosphatidylcholine ion; [(CH) n H2O4P] - [where n=0, 1, 2 or 3].

[0030] In one embodiment, silicon-organic agent 1 contains the following ions in its agent-specific MCR loading: silane species, silicon-carbon species, formula [OSiR1R2] n -wherein R1 and R2 are independently selected from methyl, ethyl, and propyl, and n is any integer from 2 to 10.

[0031] In one embodiment, the silicon-inorganic agent 1 comprises one or more of the following ions in its agent-specific MCR loading: silicon species; aluminum and / or boron species; halogen species.

[0032] In one embodiment, lipid factor 1 has the following ions in its factor-specific MCR loading: [C 10 H 17 O2] - , [C 10 H 19 O2] - , [C 12 H 21 O2] - , [C 16 H 29 O2] - , [C 16 H 31 O2] - , [C 16 H 32 O2] - , [C 18 H 31 O2] - , [C 18 H 33 O2] - , [C 18 H 35 O2] - , [PO3] - , [PH2O4] - , [CH3O4P] - , [C2H4O4P] - Contains one or more of the following:

[0033] In one embodiment, silicon-organic agent 1 contains the following ions in its agent-specific MCR loading: [SiC] - [SiCHO] - , [SiCH3O2] - , [SiC2H5O] - , [Si2CHO2] - , [SiC3H9O] -, [Si2CH 15 O2] - , [Si3CH 15 O4] - Contains one or more of the following:

[0034] In one embodiment, the silicon-inorganic factor 1 has the following ions in its factor-specific MCR loading: OH - , Al - , Si - , P - , Cl - , NaO - , AlO - , BO2 - , SiHO - , AlO2 - , SiO2 - , SiH5O2 - , Si3H3O2 - , Si2HO5 - Contains one or more of the following:

[0035] In one embodiment, lipid factor 1 has the following ions in its factor-specific MCR loading: [C 10 H 19 O2] - , [C 12 H 21 O2] - , [C 16 H 29 O2] - , [C 16 H 31 O2] - , and [C 18 H 35 O2] - Includes at least five of the following:

[0036] In one embodiment, silicon-organic agent 1 has the following ion in its agent-specific MCR loading: [SiCHO] - , [SiCH3O2] - , [SiC2H5O] - , [SiC3H9O] - and [Si2C5H 15 O2] - Includes at least five of the following:

[0037] In one embodiment, the silicon-inorganic factor 1 contains the following ions in its factor-specific MCR loading: OH - , Si - , SiO2 - , SiH5O2 - and Si3H3O2 - Includes at least five of the following:

[0038] In the method, the step of evaluating the scores of one or more factors by comparison with a reference score comprises: - obtaining a reference score from a reference container; and / or - obtaining reference values ​​for said scores, for example from the literature Contains one or more of the following:

[0039] As used herein, a "reference container" may be an uncoated container. The reference container may be of the same dimensions and material and bulk composition as the pharmaceutical container. For example, the pharmaceutical container may be coated, whereas the reference container may be uncoated.

[0040] In one embodiment of the method, the step of evaluating the scores of one or more factors by comparison to a reference score comprises: - comparing the score of the pharmaceutical container, e.g. the lipid factor 1 score, to a reference score; - assessing whether the difference between the score of the pharmaceutical container, e.g. the lipid factor 1 score, and a reference score, e.g. the lipid factor 1 reference score, is below or above a pre-defined threshold, and / or - assessing whether the quotient of the score of the drug container, e.g. the lipid factor 1 score, and the reference score, e.g. the lipid factor 1 reference score, is below or above a pre-defined threshold value. Contains one or more of the following:

[0041] In one embodiment of the method, the evaluation results in a positive or negative answer indicating suitability or disapproval, respectively.

[0042] In one embodiment of the method, the comparison to the reference pharmaceutical container comprises: - providing a reference container having an interior surface and an exterior surface, at least a portion of the interior surface being covered with a coating, the reference container having the same dimensions and the same composition as the pharmaceutical container; - incubating the reference vessel with a lipid-based carrier system; - acquiring ToF-SIMS data from an inner surface of the reference vessel; - selecting between 10 and 1000 signals from the ToF-SIMS data; - performing a multivariate spectral resolution (MCR) analysis on the ToF-SIMS data to obtain one or more factors; - obtaining a score corresponding to one or more factors from the MCR analysis; and - assessing whether the difference between the score of one or more factors of the drug container and the score of one or more factors of a reference drug container is below or above a pre-defined threshold; or - assessing whether a quotient of the score of one or more factors of the drug container and the score of one or more factors of a reference drug container is below or above a pre-defined threshold value. Includes.

[0043] Related Aspects Advantageously, the method according to the invention can be adapted to select relevant individual factors, such as lipid factor 1, silicon-organic factor 1, silicon-inorganic factor 1 and organic factor 1. The ToF-SIMS data acquired from the inner surface of the container covers a large number of molecular (ion) species / masses, most of which belong to at least one well-defined compound group covered by the factors. The ToF-SIMS data can be subjected to MCR (multivariate spectral decomposition) analysis on the ToF-SIMS data with the selected factors, allowing direct comparison of the pharmaceutical container with the reference pharmaceutical container by corresponding scores.

[0044] It is advantageous to directly compare the scores of the container and the reference container by computational calculation and subsequent evaluation of the computational results, which can be performed for individual factors, but can also be used for combinations of several individual factors.

[0045] In a related aspect, the invention provides a method for evaluating the suitability of a pharmaceutical container for a lipid-based carrier system, comprising the steps of: - providing a pharmaceutical container having an interior surface and an exterior surface, at least a portion of the interior surface being coated with a coating; - incubating the container with a lipid-based carrier system; - acquiring ToF-SIMS data from the interior surface of the vessel; - selecting between 10 and 1000 signals from the ToF-SIMS data; - performing a factor-based MCR (multivariate spectral resolution) analysis on the ToF-SIMS data; - selecting one or more factors, including lipid factor 1; - obtaining scores corresponding to the factors from the MCR analysis; - dividing the factor score by the similarity score of the reference drug container to obtain a lipid factor 1 quotient; and - assessing the suitability of the pharmaceutical container for a lipid-based carrier system based on a criterion of whether the lipid factor 1 quotient is less than 0.5. The present invention relates to a method comprising the steps of:

[0046] In a related aspect, the invention provides a method for evaluating the suitability of a pharmaceutical container for a lipid-based carrier system, comprising the steps of: - providing a pharmaceutical container having an interior surface and an exterior surface, at least a portion of the interior surface being coated with a coating; - incubating the container with a lipid-based carrier system; - acquiring ToF-SIMS data from the interior surface of the vessel; - selecting between 10 and 1000 signals from the ToF-SIMS data; - performing a factor-based MCR (multivariate spectral resolution) analysis on the ToF-SIMS data; - selecting one or more agents comprising a silicon-organic agent 1; - obtaining scores corresponding to the factors from the MCR analysis; - dividing the factor score by the similarity score of the reference drug container to obtain a silicon-organic factor 1 quotient; and - assessing the suitability of the pharmaceutical container for the lipid-based carrier system based on the criterion that the silicon-organic factor 1 quotient is greater than 2.0. The present invention relates to a method comprising the steps of:

[0047] In a related aspect, the invention provides a method for evaluating the suitability of a pharmaceutical container for a lipid-based carrier system, comprising the steps of: - providing a pharmaceutical container having an interior surface and an exterior surface, at least a portion of the interior surface being coated with a coating; - incubating the container with a lipid-based carrier system; - acquiring ToF-SIMS data from the interior surface of the vessel; - selecting between 10 and 1000 signals from the ToF-SIMS data; - performing a factor-based MCR (multivariate spectral resolution) analysis on the ToF-SIMS data; - selecting one or more agents, including an organic agent 1; - obtaining scores corresponding to the factors from the MCR analysis; - dividing the factor score by the similarity score of the reference drug container to obtain an organic factor 1 quotient; and - assessing the suitability of the pharmaceutical container for the lipid-based carrier system based on the criterion that the organic factor 1 quotient is greater than 0.2. The present invention relates to a method comprising the steps of:

[0048] In one embodiment of the method, the suitability of the pharmaceutical container is determined by: - assessing the suitability of the pharmaceutical container for a lipid-based carrier system based on the criterion that the lipid factor 1 quotient is less than 0.5; and - To assess the suitability of drug containers for lipid-based carrier systems based on the criterion of whether the silicon-organic factor 1 quotient is greater than 2.0 is evaluated based on.

[0049] Drug containers with a low lipid factor 1 quotient and a high silicon-organic factor 1 quotient can be considered very suitable for lipid-based carrier systems, as the results show little adsorption of the lipid-based carrier and its individual components, and existing coatings of the drug container remain intact. An intact coating of the drug can be demonstrated by silicon-organic species such as siloxanes, which are intended to prevent the lipid-based carrier from adsorbing to glass.

[0050] In one embodiment of the method, the suitability of the pharmaceutical container is determined by: - assessing the suitability of the pharmaceutical container for a lipid-based carrier system based on the criterion that the lipid factor 1 quotient is less than 0.5; and - To assess the suitability of drug containers for lipid-based carrier systems based on the criterion that the organic factor 1 quotient is greater than 0.2 is evaluated based on.

[0051] Similarly, a pharmaceutical container with a low lipid factor 1 quotient and a high organic factor 1 quotient can be considered highly suitable for a lipid-based carrier system, as the results show little adsorption of the lipid-based carrier and its individual components, and the pharmaceutical polymer container remains intact. An intact polymer container can be demonstrated by organic species emanating from the polymer itself.

[0052] container The following disclosure relates to pharmaceutical containers and / or reference containers.

[0053] In one embodiment, the container is a glass container or a polymeric container.

[0054] In one embodiment, the container comprises a cyclic olefin copolymer.In one embodiment, the container comprises a cyclic olefin polymer.

[0055] In one embodiment, the container has the following characteristics: - Wall thickness of 0.50-10.0mm or 1.00-4.00mm, and / or - the volume of the container is from 0.1 ml to 1000 ml, from 0.5 ml to 500 ml, from 1 ml to 250 ml, from 2 ml to 30 ml, from 2 ml to 15 ml, or from about 1 ml, 2 ml, 3 ml, 4 ml, 5 ml, 6 ml, 7 ml, 8 ml, 9 ml, 10 ml, 11 ml, 12 ml, 13 ml, 14 ml or 15 ml, optionally from 5 ml to 15 ml has one or more of the following.

[0056] In one embodiment, the container has a wall thickness of 0.50 mm or more, 1.00 mm or more, or 2.0 mm or more. In one embodiment, the container has a wall thickness of 10.0 mm or less, or 7.00 mm or less, or 4.0 mm or less.

[0057] In one embodiment, the container is a syringe, cartridge, ampoule or vial.

[0058] Glass composition The following disclosure relates to pharmaceutical containers and / or reference containers.

[0059] In one embodiment, the container has a glass composition comprising 50-90 wt. % SiO2 and 3-25 wt. % B2O3.

[0060] In one embodiment, the container has a glass composition comprising an aluminosilicate, optionally comprising 55-75 wt. % SiO2 and 11.0-25.0 wt. % Al2O3.

[0061] In one embodiment, the container has a glass composition comprising 70-81 wt.% SiO2, 1-10 wt.% Al2O3, 6-14 wt.% B2O3, 3-10 wt.% Na2O, 0-3 wt.% K2O, 0-1 wt.% Li2O, 0-3 wt.% MgO, 0-3 wt.% CaO, and 0-5 wt.% BaO.

[0062] In one embodiment, the container has a glass composition comprising 72-82 wt.% SiO2, 5-8 wt.% Al2O3, 3-6 wt.% B2O3, 2-6 wt.% Na2O, 3-9 wt.% K2O, 0-1 wt.% Li2O, 0-1 wt.% MgO, and 0-1 wt.% CaO.

[0063] In one embodiment, the container has a glass composition including 60-78 wt.% SiO2, 7-15 wt.% B2O3, 0-4 wt.% Na2O, 3-12 wt.% K2O, 0-2 wt.% Li2O, 0-2 wt.% MgO, 0-2 wt.% CaO, 0-3 wt.% BaO, and 4-9 wt.% ZrO2.

[0064] In one embodiment, the container has a glass composition including 50-70 wt.% SiO2, 10-26 wt.% Al2O3, 1-14 wt.% B2O3, 0-15 wt.% MgO, 2-12 wt.% CaO, 0-10 wt.% BaO, 0-2 wt.% SrO, 0-8 wt.% ZnO, and 0-2 wt.% ZrO2.

[0065] In one embodiment, the container has a glass composition including 55-70 wt.% SiO2, 11-25 wt.% Al2O3, 0-10 wt.% MgO, 1-20 wt.% CaO, 0-10 wt.% BaO, 0-8.5 wt.% SrO, 0-5 wt.% ZnO, 0-5 wt.% ZrO2, and 0-5 wt.% TiO2.

[0066] In one embodiment, the container has a glass composition comprising 65-72 wt. % SiO2, 11-17 wt. % Al2O3, 0.1-8 wt. % Na2O, 0-8 wt. % K2O, 3-8 wt. % MgO, 4-12 wt. % CaO, and 0-10 wt. % ZnO.

[0067] In one embodiment, the container has a glass composition including 64-78 wt.% SiO2, 4-14 wt.% Al2O3, 0-4 wt.% B2O3, 6-14 wt.% Na2O, 0-3 wt.% K2O, 0-10 wt.% MgO, 0-15 wt.% CaO, 0-2 wt.% ZrO2, and 0-2 wt.% TiO2.

[0068] Further embodiments In one embodiment, the method comprises: - providing a pharmaceutical container; and - applying the results of the method for evaluating the suitability of a pharmaceutical container for a lipid-based carrier system. Includes.

[0069] In one embodiment, the method comprises: - providing a pharmaceutical container and a reference container; and - applying the results of the method for evaluating the suitability of a pharmaceutical container for a lipid-based carrier system. Includes.

[0070] In one embodiment, the method comprises: - providing a pharmaceutical container and a reference container; and - applying the results of the method for evaluating the suitability of a pharmaceutical container for a lipid-based carrier system to determine the suitability of the pharmaceutical container for a lipid-based carrier system. Includes.

[0071] In one embodiment, the method comprises: - providing a pharmaceutical container and a reference container; and - determining the suitability of the pharmaceutical container for a lipid-based carrier system using the results of the method for evaluating the suitability of the pharmaceutical container for a lipid-based carrier system. Includes.

[0072] One embodiment of the present disclosure comprises: - evaluating the suitability of the coated container for the storage of pharmaceutical products, preferably lipid-based carrier systems, using the results of the evaluation obtainable by the method according to the present disclosure, and / or - evaluating the adhesion of the lipid-based carrier system or parts thereof to the coated container, preferably the coated pharmaceutical container, using the results of the evaluation obtainable by the method according to the present disclosure; and / or - connecting and / or coupling the results of the evaluation obtainable by the method according to the present disclosure to the coated container, preferably the coated pharmaceutical container. The present invention relates to a method comprising the steps of:

[0073] A further method of the present disclosure comprises: - manufacturing the first and second coated vessels by the same manufacturing method; - evaluating the first coated container by a method according to the present disclosure to obtain a result of the evaluation of the first coated container; and - applying and / or using the results of the evaluation of the first coated container to determine the suitability of the second coated container for storage of a pharmaceutical composition, preferably for storage in the second container, and / or using the results of the evaluation for quality control of the first and / or second container, and / or - applying and / or using the results of the evaluation of the first coated container to determine the suitability of the second coated container for storage of the lipid-based carrier system, preferably for storage in the second container. Includes.

[0074] One aspect of the present disclosure relates to the use of the results of the evaluation obtainable by the method according to the present disclosure for evaluating the suitability of a coated container, preferably a coated pharmaceutical container, for the storage of a pharmaceutical composition, preferably a pharmaceutical composition comprising a lipid-based carrier system, and / or for the quality control of the manufacture of the coated container.

[0075] Another embodiment is a pharmaceutical container bearing, for example on a label, one or more results of a method according to the present disclosure, optionally comprising: - indication of the suitability of the container for the storage of lipid-based carrier systems, - MCR factors and / or scores, - after evaluation according to any one of claims 1 to 31, - Score for lipid factor 1, silicon-organic factor 1, silicon-inorganic factor 1 and / or organic factor 1 The present invention relates to a pharmaceutical container.

[0076] The present disclosure relates to i) a coated vessel, e.g., a coated vessel according to the present disclosure, and ii) A data sheet or storage medium containing the results of the evaluation obtainable by the method according to the present disclosure. The present invention also relates to a kit comprising:

[0077] LNP incubation Any reference to "LNP-incubated" in this disclosure means that the container or coating is incubated with LNP before measurement. When a score is shown as a "relative" score ratio, it should be understood that each value is a relative ratio of the score value of the coated container divided by the score value of a non-coated reference container based on the same MCR factor. For example, to measure the relative LNP-incubated MCR score ratio of a coated container and a non-coated container that is a reference container, both containers are incubated with the same specific LNP composition that is applied to the coated container. Both the coated container and the reference container are analyzed by ToF-SIMS and MCR to obtain an absolute MCR score, for example, the absolute MCR score of lipid factor 1. The relative LNP-incubated MCR score ratio, for example, the relative LNP-incubated MCR score ratio of lipid factor 1, is obtained by dividing the obtained MCR score of the coated container by the MCR score of the reference container. For example, the relative LNP-incubated MCR score ratio of lipid factor 1 can be less than 0.5. As mentioned above, the reference container can be a non-coated container. The reference vessel may be of the same dimensions and material and bulk composition as the coated vessel (excluding the coating, of course).

[0078] In one embodiment, LNP incubation of a glass vessel, either an uncoated or coated glass vessel, comprises washing the vessel with ultrapure water (equivalent to purity 1, DIN ISO 3696, ≦0.1 μS / cm at 25° C.), drying under laminar flow conditions, filling the vessel with the reference LNP composition, freezing to −80° C., incubating at −80° C. for 12 hours, and then thawing to 5° C. within 12 hours to incubate the vessel with the reference LNP composition, followed by emptying the contents and then rinsing 10 times with ultrapure water to perform a cleaning step of the interior surface of the vessel, followed by drying under laminar flow.

[0079] In a related embodiment, LNP incubation of a polymer container, either an uncoated or coated polymer container, comprises incubating the container with the reference LNP composition by filling the container with the reference LNP composition, freezing to -80°C, incubating at -80°C for 12 hours, and then thawing to 5°C within 12 hours, followed by emptying the contents and a cleaning step of the interior surface of the container by rinsing 10 times with ultrapure water, followed by drying under laminar airflow.

[0080] In one embodiment, the drug container comprises 7×10 13 Less than 5×10 13 Less than or 2×10 13 have an absolute LNP incubation MCR score of less than lipid factor 1. Assessment of suitability of a pharmaceutical container for a lipid-based carrier can be based on this criterion and a specified score value, i.e., if the score is within the specified range, the container can be considered suitable.

[0081] In one embodiment, the pharmaceutical container has a lipid factor 1 relative LNP incubation MCR score ratio of less than 0.67, less than 0.5, less than 0.3, or less than 0.13. Assessment of suitability of the pharmaceutical container for lipid-based carriers can be based on this criterion and a designated score value, i.e., if the score is within the designated range, the container can be considered suitable. In one embodiment, the pharmaceutical container has a lipid factor 1 relative LNP incubation MCR score ratio of less than 0.67, less than 0.5, less than 0.3, or less than 0.13. 12and / or a silicon-organic agent 1 relative LNP incubation MCR score ratio of at least 2. Assessment of suitability of a pharmaceutical container for a lipid-based carrier can be based on this criterion and a specified score value, i.e., if the score is within the specified range, the container can be considered suitable.

[0082] In one embodiment, the pharmaceutical container contains up to 1×10 13 , up to 5×10 12 or up to 3×10 12 Optionally, the score is at least 0.5×10 12 An assessment of the suitability of a pharmaceutical container for a lipid-based carrier can be based on this criteria and a designated score value, i.e., if the score is within a designated range, the container can be considered suitable.

[0083] In one embodiment, the relative LNP incubation MCR score ratio of silicon-inorganic agent 1 is at most 5, at most 3 or at most 1.5. Optionally, this score ratio is at least 0.1 or at least 0.2. The suitability of the pharmaceutical container for the lipid-based carrier can be assessed based on this criterion and a designated score value, i.e., if the score is within a designated range, the container can be considered suitable.

[0084] In one embodiment, the pharmaceutical container contains at least 1×10 12 , at least 2 × 10 12 or at least 3×10 12 Optionally, the silicon-organic agent 1 absolute LNP incubation MCR score is up to 9×10 13 , up to 7×10 13 or up to 6×10 13An assessment of the suitability of a pharmaceutical container for a lipid-based carrier can be based on this criterion and a designated score value, i.e., if the score is within the specified range, the container can be considered suitable.

[0085] In one embodiment, the pharmaceutical container has a silicon-organic agent 1 relative LNP incubation MCR score ratio of at least 2, at least 3, or at least 5. Optionally, the silicon-organic agent 1 relative LNP incubation MCR score ratio can be up to 20, up to 15, or up to 10. The suitability of the pharmaceutical container for the lipid-based carrier can be assessed based on this criterion and a designated score value, i.e., if the score is within the designated range, the container can be considered suitable.

[0086] In one embodiment, the pharmaceutical container contains at least 1×10 13 and / or a silicon-to-inorganic agent 1 relative LNP incubation MCR score ratio of up to 5. Assessment of suitability of a pharmaceutical container for a lipid-based carrier can be based on this criterion and the designated score value, i.e., if the score is within the designated range, the container can be considered suitable.

[0087] In one embodiment, the container contains at least 1×10 12 and / or an organic factor 1 relative LNP incubation MCR score ratio of at least 0.2. Assessment of suitability of a pharmaceutical container for a lipid-based carrier can be based on this criterion and a specified score value, i.e., if the score is within the specified range, the container can be considered suitable.

[0088] Optionally, the container can be up to 9×10 12 , up to 8×10 12 or up to 6×10 12has an absolute LNP incubation MCR score of organic factor 1. Assessment of suitability of a pharmaceutical container for a lipid-based carrier can be based on this criterion and a specified score value, i.e., if the score is within the specified range, the container can be considered suitable.

[0089] Alternatively or additionally, the vessels may have corresponding non-LNP incubated score values, which are obtained without LNP incubation ("non-incubated").

[0090] The absolute unincubated MCR score for silicon-organic factor 1 is at least 3 × 10 12 , at least 5 × 10 12 Or at least 7×10 12 Optionally, the absolute unincubated MCR score of silicon-organic agent 1 can be up to 9×10 13 , up to 7×10 13 or up to 6×10 13 An assessment of the suitability of a pharmaceutical container for a lipid-based carrier can be based on this criterion and a designated score value, i.e., if the score is within the specified range, the container can be considered suitable.

[0091] The relative unincubated MCR score ratio for silicon-organic factor 1 is at least 3 × 10 12 , at least 5 × 10 12 Or at least 7×10 12 Optionally, the absolute LNP incubation MCR score for silicon-organic agent 1 can be up to 9×10 13 , up to 7×10 13 or up to 6×10 13 An assessment of the suitability of a pharmaceutical container for a lipid-based carrier can be based on this criterion and a designated score value, i.e., if the score is within the specified range, the container can be considered suitable.

[0092] The absolute unincubated MCR score for silicon-inorganic factor 1 is up to 1 × 10 13 , up to 5×1012 or up to 3×10 12 Optionally, the score may be at least 0.5×10 12 An assessment of the suitability of a pharmaceutical container for a lipid-based carrier can be based on this criteria and a designated score value, i.e., if the score is within a designated range, the container can be considered suitable.

[0093] The relative non-incubated MCR score ratio of silicon-inorganic agent 1 can be up to 5, up to 3 or up to 1.5. Optionally, this score ratio is at least 0.1 or at least 0.2. The suitability of the pharmaceutical container for the lipid-based carrier can be evaluated based on this criterion and the designated score value, i.e., if the score is within the designated range, the container can be considered suitable.

[0094] In one embodiment, the assessment of suitability of a pharmaceutical container for a lipid-based carrier may be based on one or more or all of the above criteria / score values. [Brief description of the drawings]

[0095] [Figure 1] Figure 1 shows photographs obtained from uncoated and coated glass vials. The glass vials were prepared using glass tubing (Fiolax® clear, Schott AG, Germany) and exposed to a reference solution and a solution containing LNPs. [Figure 2A] FIG. 1 shows characteristic lipid factor 1 loadings obtained from the data matrix of negative ToF-SIMS spectra of lipid-containing compounds adsorbed on the inner surface of a glass vial. [Figure 2B] Figure 2B shows the score values ​​obtained for coated and uncoated glass vials from the MCR analysis based on lipid factor 1 with the loadings shown in Figure 2 A. Each experiment was performed in duplicate on both the bottom and near-bottom walls of the inner glass vial surface. [Figure 3A]FIG. 1 shows characteristic lipid factor 1 loading obtained from a data matrix of negative ToF-SIMS spectra of lipid-containing compounds adsorbed on the inner surface of coated and uncoated polymer syringes made from COC polymer. [Figure 3B] Figure 3B shows the score values ​​obtained for coated and uncoated polymeric syringes from the lipid factor based MCR analysis with the loading of Figure 3 A. Each experiment was performed in duplicate on both the bottom and near-bottom walls of the inner surface. [Figure 4A] FIG. 1 shows characteristic silicon-organic agent 1 loadings obtained from a data matrix of negative ToF-SIMS spectra of silicon-organic compounds on the inner surfaces of coated and uncoated glass vials, glass syringes and polymer syringes. [Figure 4B] FIG. 4B shows the score values ​​obtained for coated and uncoated vessels from the MCR analysis of the data matrix shown in FIG. 4A. Each experiment was performed in duplicate on both the bottom and near-bottom walls of the inner surface. [Figure 5A] FIG. 13 shows a list of ion species selected from raw ToF-SIMS data with intensities obtained from a glass container. [Figure 5B] FIG. 13 shows a list of selected ion species from raw ToF-SIMS data with intensities obtained from a polymer container. [Figure 6A] FIG. 1 shows characteristic silicon-inorganic factor 1 loadings obtained from the data matrix of negative ToF-SIMS spectra of silicon-inorganic compounds on the inner surface of coated and uncoated glass vials. [Figure 6B] FIG. 6B shows the score values ​​obtained for coated and uncoated vessels from the MCR analysis of the data matrix shown in FIG. 6A. Each experiment was performed in duplicate on both the bottom and near-bottom walls of the inner surface. [Figure 7A] FIG. 1 shows characteristic organic factor 1 loadings obtained from the data matrix of negative ToF-SIMS spectra of organic compounds on the inner surface of coated and uncoated glass vials. [Figure 7B]FIG. 7B shows the score values ​​obtained for coated and uncoated glass vials from the MCR analysis of the data matrix shown in FIG. 7A. Each experiment was performed in duplicate on both the bottom and near-bottom walls of the inner surface.

[0096] Methods and Examples Preparation of glass vessels Coated and uncoated glass containers (the latter being the reference container), both having the same dimensions, glass type and glass composition, are treated under exactly the same conditions.

[0097] To measure the LNP incubation MCR score, each container is washed with ultrapure water (equivalent to purity 1, DIN ISO 3696, ≦0.1 μS / cm at 25° C.) and dried under laminar flow conditions. The containers are then filled with a reference LNP composition, frozen to −80° C., incubated at −80° C. for 12 hours, and then thawed to 5° C. within 12 hours.

[0098] In a first variant, the reference LNP composition is the Comirnaty vaccine (license number EU / 1 / 20 / 1528).

[0099] In a second variation, the reference LNP contains the following lipids in the indicated amounts in phosphate buffered saline (PBS) (pH 7.4) with 10% saccharide content by weight and the following concentrations: 7.2 mg / mL (4-hydroxybutyl)azanediyl)bis(hexane-6,1-diyl)bis(2-hexyldecanoate), 0.83 mg / mL 2[(polyethylene glycol)-2000]-N,N-ditetradecylacetamide, 1.5 mg / mL 1,2-distearoyl-sn-glycero-3-phosphocholine, and 3.3 mg / mL cholesterol.

[0100] [Table 3]

[0101] Both vessels are analyzed by ToF-SIMS and MCR analysis (see next section).

[0102] Absolute LNP incubation MCR score means the MCR score obtained for a particular factor from a single vessel, either a coated or uncoated (reference) glass vessel, where the factors are selected from lipid factor 1, silicon-organic factor 1, silicon-inorganic factor 1 and organic factor 1, each factor having a factor-specific MCR loading.

[0103] The relative LNP incubation MCR score ratio refers to the quotient of the MCR scores of a particular agent between the coated and uncoated (reference) glass vessels.

[0104] Preparation of polymer container Coated and uncoated polymeric containers, both having the same dimensions, glass type and glass composition, are treated under identical conditions.

[0105] The preparation of the polymer vessels is identical to that of the glass vessels, except for omitting the washing with ultrapure water (corresponding to purity 1, DIN ISO 3696, ≦0.1 μS / cm at 25° C.) and drying under laminar flow conditions.

[0106] ToF-SIMS (time-of-flight secondary ion mass spectrometry) In the following, the measurement method and data evaluation of specific ToF-SIMS measurements are described in detail. The measurements were performed using an Iontof TOF.SIMS 4. Unless otherwise stated, ToF-SIMS measurements are performed according to ASTM E 1829 and ASTM E 2695.

[0107] measurement The following parameter settings were used for the ToF-SIMS analysis: Primary ion: Ga + ;(alternatively TOF.SIMS 5 and Bi + using ); (Primary ion) energy: 25000V; Measurement area: 100×100μm2 ; Primary ion dose density: 6×10 12 cm -2 ; Surface discharge: caused by low energy electrons.

[0108] Spectral data was acquired for 100 seconds and then integrated.

[0109] Sample preparation Each sample of the (coated) container was cut in two lengthwise and positioned so that the centerline of the primary ion gun of the ToF-SIMS instrument struck the inner surface of the sample. The thus generated, essentially ionized secondary ions were analyzed by time-of-flight analysis and separated into different detectable mass / charge ratios. Thus, high-resolution mass spectra (Δm / m>3000 for Si) covering both atomic and molecular ion species are obtained. The die surface sensitivity covers several monolayers.

[0110] Prepare your data The ToF-SIMS data contains n data sets consisting of ion specific masses and their corresponding intensities. The ion species / masses are selected from the raw ToF-SIMS data including intensities as shown in Figure 5A and Figure 5B for glass and polymer containers, respectively. As the experiment is performed in negative mode, the ion specific masses relate only to negative ions. For the interpretation of the masses, the spectral library of IONTOF GmbH can be used. All ion species / masses are normalized according to their respective variances.

[0111] Multivariate Spectral Resolution (MCR) To identify the MCR factors, the ToF-SIMS results are subjected to a subsequent multivariate analysis by MCR (multivariate spectral resolution). MCR is a method of statistical analysis in which the binary data matrix D (m × n) is divided into two matrices C (m × k) and S (m × k) that contain the pure concentration profile and the pure spectrum of k species of the unknown mixture, respectively. T (k×n), the formula D=CS T+E, where E is the error matrix containing the residuals of the data (Ruckebusch & Blanchet, Analytica Chimica Acta 765, 2013, 28-36). The MCR method has been adapted for the decomposition and analysis of ToF-SIMS. For this task, commercially available software can be used, for example the software package SurfaceLab Ver 7.1., optionally setting the number of factors to 3, 4 or 5. A general description of how the spectral information can be analyzed in detail is given by Juan & Tauler (Analytica Chimica Acta 1145, 2021, 59-78).

[0112] In summary, ToF-SIMS results measured on a particular coating or container can be attributed to a specific location in n-dimensional compositional space. MCR is used to reduce the complexity of ToF-SIMS results by collapsing the data set into a more limited number of variables, so-called "factors". The result of MCR is a set of factors, loadings and corresponding scores. Each factor has a factor-specific MCR loading that indicates the conceptual components in the n-dimensional compositional space that can be attributed to said factor, and the loadings characterize the factor in that they list the ions that contribute to the definition of said factor. Each factor relates to a substance present in or on the coating or container. To be clear, the conceptual components are not actually present in the coating or container. Each score indicates the intensity of the corresponding factor, which correlates with the abundance of the substance in or on the coating or container.

[0113] Reference Lipid Nanoparticles (LNPs) The coated glass vials were treated with either a phosphate-buffered saline (PBS) solution or a reference LNP in the same PBS solution. The differently treated coated glass vials were subjected to ToF-SIMS measurements as described above, and data were extracted according to the MCR analysis described above.

[0114] In a first variant, the reference LNP composition was the Comirnaty vaccine (license number EU / 1 / 20 / 1528).

[0115] In a second variation, the reference LNP contained the following lipids in the indicated amounts in phosphate buffered saline (PBS) (pH 7.4) with 10% saccharide content by weight and the following concentrations: 7.2 mg / mL (4-hydroxybutyl)azanediyl)bis(hexane-6,1-diyl)bis(2-hexyldecanoate), 0.83 mg / mL 2[(polyethylene glycol)-2000]-N,N-ditetradecylacetamide, 1.5 mg / mL 1,2-distearoyl-sn-glycero-3-phosphocholine, and 3.3 mg / mL cholesterol.

[0116] [Table 4]

[0117] Further LNP formulations LNPs of similar composition may alternatively be used, and the composition may deviate from the given amounts of the individual lipid components by up to 30% by weight.

[0118] Additionally, LNPs contain RNA, such as mRNA, which is based on polynucleotides that contain adenine.

Claims

1. 1. A method for assessing suitability of a pharmaceutical container for a lipid-based carrier system, comprising: - providing a pharmaceutical container having an interior surface and an exterior surface, where at least a portion of the interior surface is coated with a coating; - incubating said container with a lipid-based carrier system; - acquiring ToF-SIMS data from the interior surface of the vessel; - selecting between 10 and 1000 signals from the ToF-SIMS data; - performing MCR (multivariate spectral resolution) analysis on selected signals from the ToF-SIMS data to obtain one or more factors; - obtaining a score corresponding to said one or more factors from said MCR analysis; and - evaluating the score of at least one of said one or more factors by comparison with a reference score A method comprising:

2. 10. The method of claim 1, wherein the pharmaceutical container is a syringe, cartridge, ampoule or vial, and the pharmaceutical container is a glass container or a polymeric container.

3. Incubating the container with a lipid-based carrier system - filling said container with a reference composition comprising a lipid-based carrier system; - storing the filled containers; - Emptying, washing and drying said container.

3. The method of claim 1 or 2, comprising:

4. - storing the filled container for at least 3 hours or at least 6 hours, - storing the filled container at a temperature below 10°C, and / or - storing the filled container at a temperature below -10°C, alternatively below -50°C; The method of claim 3.

5. 5. The method according to claim 3 or 4, wherein the container is washed, preferably with water, before filling it with the reference composition.

6. The reference composition comprises: - a lipid-based carrier system such as LNPs, water and optionally a buffer, or - containing or being the Comirnaty® vaccine preparation (license number EU / 1 / 20 / 1528), 6. A method according to any one or more of claims 3 to 5.

7. The method of any one of claims 1 to 6, wherein the one or more factors comprise a lipid factor 1, a silicon-organic factor 1, a silicon-inorganic factor 1 and / or an organic factor 1.

8. 8. The method of claim 1, wherein in the step of performing MCR analysis on the ToF-SIMS data, each factor has a factor-specific MCR loading that indicates a conceptual component in an n-dimensional composition space that can be attributed to each of the one or more factors, and the factor-specific MCR loading characterizes the one or more factors by listing ions that contribute to the definition of the factor.

9. - lipid factor 1, in its factor-specific MCR loading, contains the following ions: fatty acid ions; ｎ H ２ｎ－１ O ２ ] － [wherein n is 10, 12, 14, 16 or 18]; ｎ H ２ｎ－３ O ２ ] － [wherein n is 10, 12, 14, 16 or 18]; ｎ H ２ｎ－５ O ２ ] － [wherein n is 16 or 18]; phosphatidylcholine ion; [(CH) ｎ H ２ O ４ P] － [wherein n=0, 1, 2 or 3]; and / or Silicon-organic agent 1, in its agent-specific MCR loading, contains the following ions: silane species, silicon-carbon species, ions of the formula [OSiR １ R ２ ] ｎ － [In the formula, R １ and R ２ is independently selected from methyl, ethyl, propyl, and n is any integer from 2 to 10; and / or - silicon-inorganic agent 1 contains, in its agent-specific MCR loading, one or more of the following ions: silicon species; aluminum and / or boron species; halogen species; 9. The method according to any one of claims 1 to 8.

10. - Lipid factor 1, in its factor-specific MCR loading, contains the following ions: [C １０ H １７ O ２ ] － [C １０ H １９ O ２ ] － [C １２ H ２１ O ２ ] － [C １６ H ２９ O ２ ] － [C １６ H ３１ O ２ ] － [C １６ H ３２ O ２ ] － [C １８ H ３１ O ２ ] － [C １８ H ３３ O ２ ] － [C １８ H ３５ O ２ ] － , [PO ３ ] － , [PH ２ O ４ ] － , [CH ３ O ４ P] － [C ２ H ４ O ４ P] － and Silicon-organic agent 1, in its agent-specific MCR loading, contains the following ions: [SiC] － , [SiCH ３ O] － , [SiCH ３ O ２ ] － [SiC ２ H ５ O] － [Si ２ CHO ２ ] － [SiC ３ H ９ O] － [Si ２ C ５ H １５ O ２ ] － [Si ３ C ５ H １５ O ４ ] － and / or - Silicon-inorganic factor 1, in its factor-specific MCR loading, contains the following ions: OH － , Al － , Si － , P － , Cl － , NaO － , AlO － , B.O. ２ － , SiHO － , AlO ２ － , SiO ２ － , SiH ５ O ２ － , Si ３ H ３ O ２ － , Si ２ H.O. ５ － including one or more of 10. The method according to any one of claims 1 to 9.

11. - lipid factor 1, in its factor-specific MCR loading, contains at least the following ions: [C １０ H １９ O ２ ] － [C １２ H ２１ O ２ ] － [C １６ H ２９ O ２ ] － [C １６ H ３１ O ２ ] － and [C １８ H ３５ O ２ ] － Including, Silicon-organic agent 1 has at least the following ions in its agent-specific MCR loading: [SiCH ３ O] － , [SiCH ３ O ２ ] － [SiC ２ H ５ O] － [SiC ３ H ９ O] － and [Si ２ C ５ H １５ O ２ ] － and / or - silicon-inorganic factor 1, in its factor-specific MCR loading, contains at least the following ions: OH － , Si － , SiO ２ － , SiH ５ O ２ － and Si ３ H ３ O ２ － Including, 11. The method according to any one of claims 1 to 10.

12. evaluating said scores of said one or more factors by comparison with a reference score, - obtaining a reference score from a reference container, and / or - obtaining a reference value for said score, for example from the literature The method of any one of claims 1 to 11, comprising one or more of the following steps:

13. evaluating said scores of said one or more factors by comparison with a reference score, - comparing said score of said pharmaceutical container, e.g. said score of lipid factor 1, with said reference score; - assessing whether the difference between the score of the pharmaceutical container, e.g. the score of lipid factor 1, and the reference score, e.g. the reference score of lipid factor 1, is below or above a pre-defined threshold, and / or - assessing whether the quotient of the score of the pharmaceutical container, e.g. the score of lipid factor 1, and the reference score, e.g. the reference score of lipid factor 1, is below or above a pre-defined threshold value. The method of any one of claims 1 to 12, comprising one or more of the following steps:

14. 14. A method according to any one of claims 1 to 13, wherein the evaluation results in a positive or negative answer indicating suitability or disapproval, respectively.

15. Comparison with a reference score - providing a reference container having an inner surface and an outer surface, where optionally at least a portion of said inner surface is covered with a coating, said reference container having the same dimensions and the same composition as said pharmaceutical container; - incubating said reference vessel with a lipid-based carrier system, - acquiring ToF-SIMS data from the inner surface of the reference vessel; - selecting between 10 and 1000 signals from the ToF-SIMS data; - performing MCR (multivariate spectral resolution) analysis on the ToF-SIMS data to obtain one or more factors; - obtaining a score corresponding to said one or more factors from said MCR analysis; - assessing whether the difference between the score of the one or more factors of the drug container and the score of the one or more factors of a reference drug container is below or above a pre-defined threshold, and / or - evaluating whether the quotient of the score of the one or more factors of the drug container and the score of the one or more factors of the reference drug container is below or above a pre-defined threshold value; 15. The method of any one of claims 1 to 14, comprising:

16. 1. A method for assessing suitability of a pharmaceutical container for a lipid-based carrier system, comprising: - providing a pharmaceutical container having an interior surface and an exterior surface, where at least a portion of the interior surface is coated with a coating; - incubating said container with a lipid-based carrier system; - acquiring ToF-SIMS data from the interior surface of the vessel; - selecting between 10 and 1000 signals from the ToF-SIMS data; - performing MCR (multivariate spectral resolution) analysis on the ToF-SIMS data to obtain one or more factors; - selecting one or more factors, including lipid factor 1; - obtaining a score corresponding to lipid factor 1 from said MCR analysis, - dividing said score for lipid factor 1 by the similarity score for a reference drug container to obtain a lipid factor 1 quotient; and - assessing the suitability of said pharmaceutical container for a lipid-based carrier system based on the criterion that said lipid factor 1 quotient is less than 0.

5. A method comprising:

17. 1. A method for assessing suitability of a pharmaceutical container for a lipid-based carrier system, comprising: - providing a pharmaceutical container having an interior surface and an exterior surface, where at least a portion of the interior surface is coated with a coating; - incubating said container with a lipid-based carrier system; - acquiring ToF-SIMS data from the interior surface of the vessel; - selecting between 10 and 1000 signals from the ToF-SIMS data; - performing MCR (multivariate spectral resolution) analysis on the ToF-SIMS data to obtain one or more factors; - selecting one or more agents, including a silicon-organic agent 1; - obtaining a score corresponding to silicon-organic factor 1 from said MCR analysis; - dividing said score of silicon-organic factor 1 by the similarity score of the reference drug container to obtain a silicon-organic factor 1 quotient; and - evaluating the suitability of said pharmaceutical container for a lipid-based carrier system based on the criterion that said silicon-organic factor 1 quotient is greater than 2.0; A method comprising:

18. 1. A method for assessing suitability of a pharmaceutical container for a lipid-based carrier system, comprising: - providing a pharmaceutical container having an interior surface and an exterior surface, where at least a portion of the interior surface is coated with a coating; - incubating said container with a lipid-based carrier system; - acquiring ToF-SIMS data from the interior surface of the vessel; - selecting between 10 and 1000 signals from the ToF-SIMS data; - performing MCR (multivariate spectral resolution) analysis on the ToF-SIMS data to obtain one or more factors; - selecting one or more agents, including an organic agent 1; - obtaining a score corresponding to organic factor 1 from said MCR analysis, - dividing said score of organic factor 1 by the similarity score of a reference drug container to obtain a quotient of organic factor 1; and - evaluating the suitability of said pharmaceutical container for a lipid-based carrier system based on the criterion that said organic factor 1 quotient is greater than 0.2; A method comprising:

19. The suitability of the pharmaceutical container is - assessing the suitability of said pharmaceutical container for a lipid-based carrier system based on the criterion that the lipid factor 1 quotient is less than 0.5; and - assessing the suitability of said pharmaceutical container for a lipid-based carrier system based on the criterion that the silicon-organic factor 1 quotient is greater than 2.0; 20. A method for assessing the suitability of a pharmaceutical container for a lipid-based carrier system according to any one or more of claims 1 to 18, comprising assessing the suitability of a pharmaceutical container for a lipid-based carrier system based on:

20. The suitability of the pharmaceutical container is - assessing the suitability of said pharmaceutical container for a lipid-based carrier system based on the criterion that the lipid factor 1 quotient is less than 0.5; and - assessing the suitability of said pharmaceutical container for lipid-based carrier systems based on the criterion that the quotient of organic factor 1 is greater than 0.2; 20. A method for assessing the suitability of a pharmaceutical container for a lipid-based carrier system according to any one or more of claims 1 to 19, comprising assessing the suitability of a pharmaceutical container for a lipid-based carrier system based on:

21. The pharmaceutical container and / or the reference container have the following characteristics: a wall thickness of 0.50 to 10.0 mm, preferably 1.00 to 4.00 mm, and / or a volume of said container of between 0.1 ml and 1000 ml, preferably between 0.5 ml and 500 ml, more preferably between 1 ml and 250 ml, more preferably between 2 ml and 30 ml, more preferably between 2 ml and 15 ml, more preferably about 1 ml, 2 ml, 3 ml, 4 ml, 5 ml, 6 ml, 7 ml, 8 ml, 9 ml, 10 ml, 11 ml, 12 ml, 13 ml, 14 ml or 15 ml, more preferably between 5 ml and 15 ml 21. A method for assessing the suitability of a pharmaceutical container for a lipid-based carrier system according to any one or more of claims 1 to 20, comprising one or more of the following steps:

22. The pharmaceutical container and / or the reference container are - 50 to 90% by weight of SiO ２ and 3 to 25% by weight of B ２ O ３ or - aluminosilicate, preferably 55-75% by weight of SiO ２ and 11.0 to 25.0 wt. % Al ２ O ３ Glass composition including 22. A method for assessing the suitability of a pharmaceutical container for a lipid-based carrier system according to any one or more of claims 1 to 21, comprising:

23. The pharmaceutical container and / or the reference container are each made of 70 to 81 wt. % SiO ２ , 1 to 10% by weight of Al ２ O ３ , 6 to 14% by weight of B ２ O ３ , 3 to 10% by weight of Na ２ O, 0 to 3% by weight of K ２ O, 0 to 1% by weight of Li ２ 23. A method for assessing the suitability of a pharmaceutical container for a lipid based carrier system according to any one or more of claims 1 to 22, wherein the glass composition comprises: 0-3 wt.% MgO, 0-3 wt.% CaO, 0-5 wt.% BaO.

24. The pharmaceutical container and / or the reference container are each made of 72 to 82 wt. % SiO ２ , 5 to 8 wt.% Al ２ O ３ , 3 to 6% by weight of B ２ O ３ , 2 to 6 wt.% Na ２ O, 3 to 9% by weight of K ２ O, 0 to 1% by weight of Li ２ 24. A method for assessing the suitability of a pharmaceutical container for a lipid-based carrier system according to any one or more of claims 1 to 23, wherein the glass has a composition comprising: 0-1 wt. % MgO, 0-1 wt. % CaO.

25. The pharmaceutical container and / or the reference container are each made of 60 to 78% by weight of SiO ２ , 7 to 15% by weight of B ２ O ３ , 0 to 4% by weight of Na ２ O, 3 to 12% by weight of K ２ O, 0 to 2 wt.% Li ２ O, 0-2 wt.% MgO, 0-2 wt.% CaO, 0-3 wt.% BaO, 4-9 wt.% ZrO ２ 25. A method for assessing the suitability of a pharmaceutical container for a lipid-based carrier system according to any one or more of claims 1 to 24, comprising:

26. The pharmaceutical container and / or the reference container are each made of 50 to 70% by weight of SiO ２ , 10 to 26 wt.% Al ２ O ３ , 1 to 14% by weight of B ２ O ３ , 0-15 wt% MgO, 2-12 wt% CaO, 0-10 wt% BaO, 0-2 wt% SrO, 0-8 wt% ZnO, 0-2 wt% ZrO ２ 26. A method for evaluating the suitability of a pharmaceutical container for a lipid-based carrier system according to any one or more of claims 1 to 25, comprising:

27. The pharmaceutical container and / or the reference container are each made of 55 to 70% by weight of SiO ２ , 11 to 25% by weight of Al ２ O ３ , 0-10% by weight MgO, 1-20% by weight CaO, 0-10% by weight BaO, 0-8.5% by weight SrO, 0-5% by weight ZnO, 0-5% by weight ZrO ２ , 0 to 5% by weight of TiO ２ 27. A method for assessing the suitability of a pharmaceutical container for a lipid-based carrier system according to any one or more of claims 1 to 26, comprising:

28. The pharmaceutical container and / or the reference container are each made of 65 to 72 wt. % SiO ２ , 11 to 17 wt.% Al ２ O ３ , 0.1 to 8% by weight of Na ２ O, 0 to 8% by weight of K ２ 28. A method for assessing the suitability of a pharmaceutical container for a lipid based carrier system according to any one or more of claims 1 to 27, wherein the glass composition comprises: 3-8 wt.% MgO, 4-12 wt.% CaO, 0-10 wt.% ZnO.

29. The pharmaceutical container and / or the reference container are each made of 64 to 78% by weight of SiO ２ , 4 to 14 wt.% Al ２ O ３ , 0 to 4% by weight of B ２ O ３ , 6 to 14% by weight of Na ２ O, 0 to 3% by weight of K ２ O, 0-10% by weight MgO, 0-15% by weight CaO, 0-2% by weight ZrO ２ , 0 to 2% by weight of TiO ２ 29. A method for assessing the suitability of a pharmaceutical container for a lipid-based carrier system according to any one or more of claims 1 to 28, comprising:

30. - evaluating the suitability of the coated container for the storage of medicinal products, preferably lipid-based carrier systems, using the results of the evaluation obtainable by the method according to any one of claims 1 to 29, and / or - evaluating the adhesion of the lipid-based carrier system or parts thereof to the coated container, preferably the coated pharmaceutical container, using the results of the evaluation obtainable by the method according to any one of claims 1 to 29, and / or - connecting and / or coupling the results of the evaluation obtainable by the method according to any one of claims 1 to 29 to a coated container, preferably a coated pharmaceutical container. A method, preferably according to any one of claims 1 to 29.

31. - manufacturing the first and second coated vessels by the same manufacturing method; - evaluating the first coated vessel by a method according to any one of claims 1 to 30 to obtain a result of the evaluation of the first coated vessel, and - applying and / or using the results of the evaluation of said first coated container to determine the suitability of said second coated container for the storage of a pharmaceutical composition, preferably for storage in said second container, and / or using the results of the evaluation for the quality control of said first and / or second containers, and / or - applying and / or using the results of the evaluation of said first coated vessel to determine the suitability of said second coated vessel for storage of a lipid-based carrier system, preferably for storage in said second vessel. A method, preferably according to any one of claims 1 to 30, comprising:

32. 30. Use of the evaluation results obtainable by the method according to any one of claims 1 to 29 for evaluating the suitability of a coated container, preferably a coated pharmaceutical container, for the storage of a pharmaceutical composition, preferably a pharmaceutical composition comprising a lipid-based carrier system, and / or for the quality control of the manufacture of the coated container.

33. 32. A pharmaceutical container having affixed thereto, for example on a label, one or more results of the method according to any one or more of the preceding claims.

34. The result is - an indication of the suitability of said container for the storage of a lipid-based carrier system, - MCR factors and / or scores, - as a result of the evaluation according to any one of claims 1 to 31, - lipid factor 1, silicon-organic factor 1, silicon-inorganic factor 1 and / or organic factor 1 scores 34. The pharmaceutical container of claim 33,

35. i) a coated vessel, preferably a coated vessel according to claim 33 or 34, and ii) A data sheet or storage medium containing the results of the evaluation obtainable by the method according to any one of claims 1 to 31. Kit including:

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