Method for manufacturing parts of machines for the manufacture and / or packaging of pharmaceutical products

Abstract

A method for manufacturing a component (10) suitable for placement in a controlled-atmosphere protective chamber (12) of a machine for manufacturing and / or packaging pharmaceutical products, the chamber (12) being configured to support one or more components, devices, or elements of a machine (11) formed by one or more components (10), and the interior of the chamber (12), i.e., the components (10) forming the machine (11), or device, or element, is subjected to a suitable decontamination and sterilization process, e.g., a CIP (clean-in-place) / SIP (sterilization-in-place) process. A method for conditioning the component (10) manufactured by the above manufacturing method and the protective chamber (12) isolated from the external environment of the machine for manufacturing and / or packaging pharmaceutical products is also described.

Description

[Technical field]

[0001] The present invention relates to a method for manufacturing components suitable for use in machines for the production and / or packaging of pharmaceutical products. [Background technology]

[0002] In particular, the invention relates to a method for manufacturing parts that are subjected to the decontamination and sterilization (CIP / SIP) treatments typically performed in this sector, which also include treatment cycles using hydrogen peroxide vapor (HPV). The invention also relates to a method for preparing a protective chamber of a machine for the manufacture and / or packaging of medicinal products in which a decontamination and sterilization treatment as described above is carried out.

[0003] In the pharmaceutical sector, processing and packaging operations of pharmaceutical products, e.g. powders, tablets, pills, liquids etc., are carried out in chambers protected and isolated from the outside environment, commonly called "isolators". The isolators are maintained in sterile conditions and a controlled atmosphere.

[0004] Handling, operating and / or packaging devices and equipment are generally located within protective chambers adapted to perform each specific operation on the pharmaceutical products in lieu of human interaction. The protective chambers, together with the instruments and devices placed inside them, must meet certain cleanliness and sterility requirements. Therefore, the chambers are generally subjected to intensive treatments to eliminate possible contaminants while maintaining the required sterility. For example, it is known to treat these chambers with hydrogen peroxide vapor. However, this treatment, while being very effective in disinfecting, sporicidal and bactericidal action, has a high oxidizing power that can damage the surfaces of the instruments inside these chambers.

[0005] To address this problem, it is known to manufacture components for instruments and devices having substrates made of lightweight materials such as substrates that are coated with a material that coats and protects the substrate.

[0006] For example, aluminum parts are known which are coated with a layer of paint, which are anodized from aluminum, or which are provided with a galvanic coating, in particular based on chromium (Cr), nickel (Ni) or other suitable metals.

[0007] Solutions are also known in which the parts are coated by immersion in a bath of metal or plastic material or resin. However, one drawback of these solutions is that the coating is applied to both the external and internal surfaces of the parts, i.e. to parts that are not exposed to sterilization or disinfection processes during use. This requires large amounts of coating material. Summary of the Invention [Problem to be solved by the invention]

[0008] One object of the present invention is to perfect a method for manufacturing isolators, components which can be used in protective chambers in the pharmaceutical sector, which overcomes at least some of the disadvantages of the state of the art.

[0009] In particular, one of the aims is to perfect the manufacturing methods for parts that are lightweight and at the same time suitable to withstand intensive decontamination processes. Another object is to complete a method for adjusting protective chambers of machines for the production and / or packaging of pharmaceutical products, which, on the one hand, reduces the time required for processing and thus the downtime of the machine, since there is no need to dismantle and / or remove the internal equipment beforehand, and, on the other hand, ensures effective decontamination of all surfaces that are placed in contact with the products to be processed during use.

[0010] Applicant has devised, evaluated and embodied the present invention to overcome the shortcomings of the state of the art and to obtain these and other objects and advantages. [Means for solving the problem]

[0011] The invention is set forth and characterized in the independent claims. The dependent claims describe further features of the invention or variants of the main invention. The embodiments described herein relate to a method for manufacturing components suitable for exposure to decontamination and sterilization processes in chambers called "isolators" of machines for the production and / or packaging of pharmaceutical products that are isolated from the external environment and maintained at a controlled atmosphere.

[0012] In one embodiment, the decontamination and sterilization process includes a CIP (clean in place) / SIP (sterilization in place) process using, for example, vaporized hydrogen peroxide (VPHP, vapor phase hydrogen peroxide). As used herein, the term "component" refers to an object that can be used alone or in combination with other components, objects, or parts of a machine to form a part of a device or equipment.

[0013] By way of non-limiting example, a "part" may be a fixed pole, a drive shaft, a transport wheel for a belt, a container, a cover, etc. , Gi Casing for a box and / or motor, joint parts of robot or part thereof , B Racket, flange, fixed or movable arm Support elements such as , mounting components such as sliders, drums, pulleys, screws, bolts, etc. etc. .

[0014] The method according to the invention makes available a part made of a first material selected from the group comprising aluminum (Al), magnesium (Mg), titanium (Ti), steel or alloys thereof, composites with a polymer matrix, carbon fibre or combinations thereof, which is placed in the chamber and comprises at least one external surface that faces outwards in the assembled and placed state of the part, i.e. is directly exposed to the air of the chamber, and that is provided at its ends with couplings adapted to couple with corresponding mating couplings provided on other parts or on the inner wall of the chamber.

[0015] The method also includes, before the part is assembled or placed in the chamber, i.e. before said joint is stably joined to a corresponding mating joint or to the inner wall of the chamber, spraying the part with a solid powder of a second material accelerated by a supersonic gas jet to deposit a coating of the second material on at least the outer surface of the part to make it suitable to withstand the above-mentioned decontamination or sterilization treatment, the second material being selected from the group consisting of one or more of stainless steel, cobalt chromium metal alloys such as Stellite, nickel alloys, materials with a polymer matrix such as polyetheretherketone (PEEK), metal-ceramic composites, carbon fiber, etc.

[0016] Parts thus coated externally with a corrosion-resistant material have surface properties suitable for withstanding CIP (cleaning in place) and / or SIP (sterilization in place) treatments, in particular in the field of pharmaceutical production and packaging. In particular, parts produced with the method according to the invention can also be subjected to treatments using hydrogen peroxide, in particular in the form of vapor VPHP (vapor phase hydrogen peroxide), as a sterilant, which is aggressive and oxidizes surfaces on contact.

[0017] According to some embodiments, the coupling portion includes a coupling edge configured to face and couple to a corresponding coupling edge of another component to form part of an apparatus or piece of equipment, or to face and couple to an inner wall of a chamber.

[0018] According to some embodiments, the joining edge is configured with a corresponding joining edge to form an interconnection of two parts with isolation from the outside environment. By "interconnected in an isolated manner" is meant in this specification the interconnection of two parts in which the possible internal surfaces of each part are separated and isolated from the external environment during use, but the possible internal compartments of the interconnected and connected parts are operatively connected to each other, but in each case isolated with respect to the outside.

[0019] According to some embodiments, the thermal spray process is a cold thermal spray process in which a solid powder of the second material is accelerated by a supersonic gas jet and applied with violent impact to the surface to be coated.

[0020] According to another embodiment, the thermal spray process is a high velocity oxygen fuel (also known as HVOF) coating spray process in which particles of a second material in molten or partially molten form are mixed with a supersonic gas stream at high temperature and high velocity and sprayed onto the surface to be coated.

[0021] Compared to other thermal spray processes, in cold spray and high velocity oxygen fuel (HVOF) coating spray processes, most of the energy delivered to the particles is kinetic rather than thermal type, which advantageously reduces the particles that oxidize during the process, resulting in a more resistant final coating.

[0022] According to some embodiments, the method involves spraying a mixture of gas and solid particles of a second material onto the exterior surface at a velocity of between 300 m / s and 1400 m / s, and holding the part in a fixed and stable position at all times by a support suitable for resisting the forces of the gas and particle mixture.

[0023] According to embodiments described herein, the method specifically involves separately spray-treating a single component to deposit a coating on at least each of the exterior surfaces and each of the bonding edges. According to some embodiments, in the case of cold spray processing, the method uses a spray nozzle mounted on an articulated arm or a numerically controlled machine having at least four axes of motion, which tracks the evolution of the surface being treated. In this way, the evolution of the outer surface and bonding edges of a single part can be accurately tracked and the spray nozzle can be directed in an appropriate manner relative to the surface being treated at all times.

[0024] According to some embodiments, the method includes spraying the material onto the surface to be treated at an angle of incidence between ±45° relative to the normal of the outer surface and / or bond edge, the angle of incidence being variable depending on the radius of curvature of the surface to be treated or on possible unevenness or corners that may be present, so as to direct the mixture of gas and particles of the second material in a targeted manner to obtain a substantially uniform coating.

[0025] According to some embodiments, the method deposits a layer of material with each spraying operation having a thickness of about 15 μm to about 100 μm. The embodiments described herein relate to a part suitable for CIP / SIP processing in a protective chamber of a machine for the production and / or packaging of pharmaceutical products, comprising couplings adapted to couple with corresponding mating couplings on other parts or on the walls of the chamber, made of a first material selected from the group consisting of aluminum (Al), magnesium (Mg), titanium (Ti), steel or alloys thereof, composites with a polymer matrix, carbon fiber, including at least one outer surface facing outward in the assembled and installed state of the part, i.e. subject to a decontamination or sterilization treatment, e.g. a CIP (cleaning in place) treatment using vaporized hydrogen peroxide (VPHP, vapor phase hydrogen peroxide) and / or a SIP (sterilization in place) treatment, and provided with a coating made of a second material selected from the group consisting of one or more of stainless steel, cobalt chromium metal alloys, nickel alloys, materials with a polymer matrix, metal ceramic composites, the coating of the second material being obtained by thermal spraying with a powder accelerated by a supersonic gas jet.

[0026] The invention also relates to a method for preparing a chamber of a machine for the production and / or packaging of pharmaceutical products, where the chamber is a protected chamber with a controlled atmosphere, isolated and separated in a sealed manner from the external environment, and adapted to receive one or more parts, devices or elements of the machine.

[0027] The method according to the invention comprises the steps of: Manufacturing a plurality of parts using a manufacturing method according to the present invention; Assembling or placing the plurality of parts at respective locations within the chamber corresponding to respective couplings configured to couple with corresponding mating couplings on another part or on an interior wall of the chamber to form at least one part of the device, or at least one device, or at least one element thereof, and to effect the function of the pharmaceutical product; placing a piece of equipment and / or a device and / or an element and / or other part in the chamber; closing the chamber so as to isolate it in a hermetically sealed manner from the external environment; The interior of the chamber, i.e. the parts, devices, elements and possibly other parts of the equipment previously placed inside the chamber, are subjected to a decontamination or sterilization treatment, such as, for example, a CIP (cleaning in place) / SIP (sterilization in place) treatment, so as to decontaminate and / or sterilize at least each outer surface of the plurality of parts and / or equipment parts and / or devices and / or elements.

[0028] As all surfaces to be decontaminated / sterilized in the chamber are pre-coated, the external surfaces of the instruments, devices and elements are not marred or damaged by the decontamination used. Therefore, the decontamination process can be repeated, if necessary, without having to remove or cover parts or devices inside the machine. This significantly reduces the time and manpower required.

[0029] According to some embodiments, CIP / SIP processing of the chamber and the parts, devices, and / or equipment disposed therein provides for performing a process using hydrogen peroxide in vapor form (VPHP, vapor phase hydrogen peroxide) as the sterilant. [Brief description of the drawings]

[0030] These and other characteristics of the invention will become apparent from the following description of some embodiments, given by way of non-limiting example with reference to the attached drawings, in which: [Figure 1]Schematic front view of a part of a machine for the production and / or packaging of pharmaceutical products, in which the preparation method according to the embodiments described herein is carried out and in which a number of components and pieces of equipment according to the invention are arranged. [Figure 2a] 3A-3C are schematic cross-sectional views of subsequent steps of a method for manufacturing a part according to embodiments described herein. [Figure 2b] 3A-3C are schematic cross-sectional views of subsequent steps of a method for manufacturing a part according to embodiments described herein. [Figure 2c] 3A-3C are schematic cross-sectional views of subsequent steps of a method for manufacturing a part according to embodiments described herein.

[0031] To facilitate understanding, wherever possible, the same part numbers have been used to identify common elements among the figures. It should be understood that elements and features of one embodiment may be incorporated in other embodiments without further specification. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0032] The embodiments described herein relate to a method for manufacturing a component 10 suitable for use in protective chambers 12 (called isolators) of machines for the production and / or packaging of pharmaceutical products, which must be isolated from the external environment in a sealed manner and meet strict sterility requirements to prevent possible contamination of the pharmaceutical products during processing.

[0033] 1, the chamber 12 is typically isolated and partitioned from the outside by a wall 13. Moreover, the chamber 12 is typically maintained at a controlled atmosphere by suitable conduits 30 configured to introduce and / or extract one or more suitable gases to the air in the chamber 12 implementing HVAC systems commonly used in many industrial applications.

[0034] It should be noted that the illustrated example involves manipulating ampoules, vials or small glass bottles in the chamber 12 suitable for containing a measured amount of a medicine. It is clear that the method of manufacturing the components and the method of preparing the isolated chamber according to the invention are independent of the type of object that is manipulated in the isolated chamber, which may be any type of container suitable for containing a medicine in addition to a syringe or a blister.

[0035] At least one of the walls 13 is provided with at least one access opening 14, usually equipped with a transfer port 15. The access opening 14 allows the protected transfer of materials inside and outside the chamber 12 and prevents direct communication between the environment inside the chamber 12 and the environment outside the chamber 12. The transfer port 15, which is subject to certification to prove compliance with current regulations, is commonly known as an alpha-beta port, or RTP, an acronym for Rapid Transfer Port. The transfer port 15 is suitable to allow the temporary connection of a closed container 31 to the wall 13 of the chamber 12. By way of example, the container 31 is used to transport vials to be filled with pharmaceutical products inside the chamber 12.

[0036] In the embodiment of Figure 1, the interior of the chamber 12 is provided with a station 26 for capping the vials, a station 27 for filling the vials, an articulated arm suitable for moving the vials, and one or more storage spaces 25 for the temporary storage of the vials. The capping station 26 and the filling station 27 each comprise a support element 28 on which the vials to be processed rest and suitable hoppers to which the liquid to be injected into the vials and the caps, respectively, are supplied.

[0037] In the following description, the term "part" means an object that can be used alone or in combination with other parts, objects or machines. By way of example, parts 10 of the type in question may be fixed columns, drive shafts, transport wheels for belts, covers, etc. , Gi Abox and / or motor casings, robot joint parts , BRacket, flange, fixed or movable arm Support elements such as , mounting components such as sliders, drums, pulleys, screws, bolts, etc. etc. .

[0038] According to some embodiments, the components 10 are assembled and coupled together to form parts and / or devices and / or elements of an apparatus 11 suitable for performing one or more operations on pharmaceutical products, including manipulating, moving, transporting, or packaging the product.

[0039] By way of example, the pieces of equipment 11 include automated handling devices such as articulated robots, i.e., generally, handling, moving, or other devices. In the example of Fig. 1, multiple pieces or devices of equipment 11 are shown formed by multiple pieces, such as, for example, storage space 25, stations 26 and 27, or articulated robots.

[0040] The components 10 and pieces of equipment 11 in question are advantageously subjected to suitable decontamination and sterilization treatment in a protective chamber 12, such as, for example, a CIP (clean in place) and / or SIP (sterilization in place) treatment using hydrogen peroxide vapor VPHP (vapor phase hydrogen peroxide) which has a high oxidizing power with bactericidal, sporicidal and germicidal action, without causing oxidation of the exterior surfaces and damage to the components 10.

[0041] According to some embodiments, each component 10 may comprise at least one coupling portion suitable for coupling with a mating coupling portion provided on another component 10 or on the inner wall 13 of the chamber 12 .

[0042] Depending on the type of part 10 in question, i.e. a single element or at least one element which, in the installed and assembled state, constitutes part of a part of the equipment 11 (or another device or element), the joint can be configured as a joint surface or a joint edge 17 or can include a plurality of both.

[0043] According to some embodiments, the joining edge 17 extends transversely to each outer surface 18 and defines a corner 24 having a substantially step-like transition. The bond may, in use, face outwardly to define the exterior surface 18 of the component 10 that is exposed to the air within the chamber 12 .

[0044] In other words, the joint substantially constitutes one side of the exterior surface 18 of the part 10 that is decontaminated and sterilized during use, and the other side of the interior surface 19 of the part 10 that is not placed in contact with the air of the chamber 12 when assembled and installed during use and therefore does not need to be decontaminated and sterilized.

[0045] According to some embodiments, the manufacturing method according to the present invention provides: a component 10 suitable for installation in a chamber 12 and / or for assembly to another component 10, comprising at least one coupling portion constituting an outer surface 18 that faces outward during use (i.e. is exposed to the air of the chamber 12) and configured to be coupled to a corresponding coupling portion of another component or to an inner wall 13 of the chamber 12, making available the component 10 made of a first material; The part 10 is thermally sprayed with a solid powder of the second material accelerated by a supersonic gas jet to deposit a coating 20 of the second material on the outer surface 18 of the part 10, which faces outward when installed in use and is CIP / SIP-treated by being exposed to the air of the chamber 12.

[0046] According to some embodiments, the component 10 in question is formed from a first light material to facilitate installation and / or removal operations of the component 10 and / or each piece of equipment 11 in the protective chamber 12 and to facilitate their transportation and movement.

[0047] According to some embodiments, the first material may be selected from the group including aluminum (Al), magnesium (Mg), titanium (Ti), steel or alloys thereof, composites with a polymer matrix, carbon fibers, or combinations thereof.

[0048] According to some embodiments, the surface finish of component 10 has a certain minimum surface roughness that allows particles sprayed during the spraying process to accumulate and remain attached to exterior surface 18 .

[0049] Preferably, the minimum surface roughness Ra of the outer surface 18 of the component 10 is comprised between about 1.6 μm and about 12.5 μm. According to some embodiments, the second material is a material suitable for resisting CIP / SIP processes, in particular VPHP (vapor phase hydrogen peroxide) processes using hydrogen peroxide vapor.

[0050] According to some embodiments, the second material may be selected from the group consisting of cobalt chromium alloys, such as stellite, nickel alloys, stainless steels, polymer matrices, such as polyetheretherketone (PEEK), metal ceramic composites, carbon fibers, or other materials suitable for undergoing decontamination and sterilization processes without being damaged or oxidized.

[0051] The coating 20 serves to protect the first material, and therefore can be selected from the lighter materials listed above, as it does not need to withstand intensive processing, and depending on the type of material used, the part 10 can be formed at a smaller thickness.

[0052] According to some embodiments, the thermal spray process can be selected between a cold spray process and a high velocity oxygen fuel (HVOF) coating spray process. According to some embodiments, the method cold sprays or HVOF treats the exterior surface 18 of the component 10 as well as each of its bond edges.

[0053] According to some embodiments, the cold spray process involves spraying a mixture of gas carrying powder or solid particles of the material used to form the coating 20 by a spray nozzle 21 towards the surface to be treated.

[0054] According to a possible solution, at least a part of the carrier gas is heated to a temperature between 200°C and 1200°C. According to an exemplary embodiment, a portion of the gas is heated and conveyed through a first conduit 22 towards the spray nozzle 21, while the remaining portion of the carrier gas is kept at room temperature, passes through a tank not shown, contains powder of the second material and is conveyed through a second conduit 23 towards the spray nozzle 21.

[0055] According to some embodiments, in the spray nozzle 21 the powder in the gas stream is accelerated and projected towards the surface to be treated at supersonic speeds, typically between 300 m / s and 1400 m / s.

[0056] According to some embodiments, the pressure of the carrier gas is between 5 bar (500 kPa) and 100 bar (10,000 kPa) depending on the type of material and the size of the particles being carried.

[0057] According to some embodiments, nitrogen or argon, for example, can be used as the carrier gas. Advantageously, the spray nozzle 21 can have a converging-diverging shape that favors the acceleration of the powder and the carrier gas.

[0058] When the accelerated particles collide with the surface to be treated, the impact determines the deformation of the treated surface and creates a stable, permanent bond between the surface and the particles of the material. According to some embodiments, each pass of the spray nozzle 21 over the surface to be treated can deposit a layer of material having a thickness of about 15 μm to about 100 μm. According to some embodiments, the method can deposit multiple overlapping layers until a coating 20 of a desired thickness is obtained.

[0059] According to some embodiments, the coating 20 can include multiple overlapping layers formed by a cold spray process, with subsequent layers being formed of the same or different materials, as desired.

[0060] According to some embodiments, a high velocity oxygen fuel (HVOF) coating spray process heats and accelerates particles of a second material by a gas flow resulting from the combustion of oxygen and fuel in a combustion chamber.

[0061] The gas stream resulting from the combustion is accelerated to a velocity of over 2000 m / s. Powder of a second material is injected into the gas stream, partially melted, accelerated to a velocity of about 1000 m / s and finally ejected through a spray nozzle 21 towards the surface to be coated. When the particles impact the surface, their high kinetic energy causes them to rapidly solidify, forming a layered structure that forms a dense coating.

[0062] According to some embodiments, even in HVOF processes, multiple overlapping layers can be deposited until a coating 20 of a desired thickness is obtained, in some cases changing the material type of subsequent layers as needed.

[0063] According to some embodiments, the method comprises thermally spray treating each part 10 before it is joined with other parts 10 to form device 11 or part of it, and before it is placed in chamber 12. In these embodiments, the heat treatment for depositing the coating on outer surface 18 and / or joining edge 17 is carried out outside chamber 12, in a suitable work center suitably equipped to carry out said heat treatment.

[0064] According to a possible embodiment, the method positions the component 10 in a stable manner during the thermal spraying process to prevent undesired movements due to pressure from the mixture of gas and particles of the second material.

[0065] According to some embodiments, the method may position and hold the components 10 in place with supports each having a mating shape, such as protecting and covering the inner surface 19 of the components 10 .

[0066] The method according to the invention uses a spray nozzle 21, for example mounted on an anthropomorphic arm or on a CNC (Computer Numerical Control) machine (not shown) having at least four axes of motion. In particular, according to some embodiments, the method uses the spray nozzle 21 at all times to track the evolution of the outer surface 18 of the part 10, and possibly of the joint.

[0067] According to some embodiments, for example as shown in FIG. 2a, the method uses a spray nozzle 21 to track the evolution of the joining edges 17 which, together with the outer surfaces 18, form substantially stepped corners 34.

[0068] According to a possible solution, the spray nozzle 21 can follow the shape of the surface to be treated, based on a path that is predefined and set based on the shape of the component to be machined.

[0069] According to a variant, the path and direction of the spray nozzle 21 can be defined in real time, for example by processing images acquired by a 3D camera mounted on the same anthropomorphic arm that supports and moves the spray nozzle 21.

[0070] According to a possible variant, it is also provided that the active part 10 and the spray nozzle 21 move in a relative motion with respect to each other, for example the active element translates in one direction and the spray nozzle 21 moves on three axes, with the combination of the respective movements providing a degree of freedom of the arm with at least four axes.

[0071] According to some embodiments, the method includes orienting a spray nozzle 21 to spray the second material at an incidence angle α comprised between ±45° relative to a direction perpendicular to the outer surface 18 and the joint, or joint edge 17 (FIG. 2a).

[0072] This angle of incidence α makes it possible to direct the mixture of gas and particles of the second material at the target so as to obtain a coating 20 of uniform thickness, even in response to possible unevenness in the surface to be treated, in particular in response to the angle 24 between the outer wall 18 and each joint and / or joint edge 17.

[0073] According to some embodiments, in the case of possible buildups of the second material form corresponding to corners 24 or possible depressions or protrusions of the outer surface 18, the method according to the invention makes it possible to remove these buildups by means of a suitable tool, substantially continuously, immediately after the deposition of the coating 20.

[0074] According to some embodiments, a tool may be positioned adjacent to the spray nozzle 21 such that the gas and particle mixture acts on the impacted surface while the spray nozzle 21 is moving.

[0075] According to some embodiments, after forming coating 20 on outer surfaces 18 and bonding edges 17 of parts 10, the method proceeds to assemble multiple parts 10 in a suitable manner to form a part of equipment 11 (or apparatus, or element) or place them in chamber 12 such that each possible inner surface 19 is protected and isolated from the outside (i.e., with respect to chamber 12) while each outer surface 18 is all facing outward and exposed to the air of chamber 12.

[0076] According to some embodiments, the method includes inserting a sealing element 26 between the joints of the two parts 10A, 10B (FIG. 2b) that are placed in contact with each other to ensure a seal between them, or between the part 10 and the wall 13 of the chamber 12.

[0077] According to some embodiments, when the component 10 includes a housing sheet 25 for a sealing element 26 on at least one bonding edge 17 (FIGS. 2a-2c), the method coats each bonding edge 17 from an outer corner 24 to at least one outer edge 27 of the housing sheet 25.

[0078] The embodiments described herein also relate to a method for preparing a protective chamber 12 of a machine for the manufacture and / or packaging of pharmaceutical products, i.e. a method for obtaining a ready-to-use, decontaminated and sterilized chamber 12 into which the pharmaceutical products to be processed and / or packaged are introduced.

[0079] According to some embodiments, the method of preparing a chamber 12 according to the present invention makes available a plurality of parts 10 manufactured outside the chamber 12 by the manufacturing method of the present invention, and provided with a coating 20 of a material suitable for being CIP / SIP processed, the coating extending on the outer surface 18 of at least each part 10 that is to be placed in the chamber 12 in an assembled and installed state and exposed to air.

[0080] The method continues by assembling the components 10 together to form a component of device 11, such as the component of device 11 of FIG. 1 and described above. According to some embodiments, the method involves bonding two or more parts 10 together and placing their bonding edges 17 facing each other. This operation is preferably performed, at least in part, outside the chamber 12 when assembling the parts of the device 11, the parts 10 with the coatings 20 being assembled to each other.

[0081] According to some embodiments, the method provides for placing each component 10 and / or piece of equipment 11 inside the chamber 12 , optionally bringing them inside through a transfer port 15 .

[0082] According to a possible variant, it is also provided that parts of the device 11 are formed directly inside the chamber 12 by bonding several parts 10 together. Subsequently, once the installation of the part 10 in the chamber 12 and the installation of the necessary parts of the equipment 11 are completed, the method according to the invention comprises closing the chamber 12, for example by closing the transfer port 15, in order to isolate it in a sealed manner from the external environment.

[0083] Finally, the method according to the invention decontaminates or sterilizes, e.g., CIP / SIP, the chamber 12 and the parts 10 and equipment 11 disposed therein to decontaminate and / or sterilize at least each of the exterior surfaces 18. As a non-limiting example, the decontamination and sterilization process uses hydrogen peroxide vapor.

[0084] Since all surfaces exposed to the decontamination sterilization process in the chamber 12 have already been coated, the exterior of the equipment 11 is not marred or damaged by the decontamination agent used. The decontamination process can therefore be repeated, if necessary, without removing or covering the parts 10 and equipment 11 in the machine, thus saving a great deal of time and manpower required.

[0085] It will be apparent that modifications and / or additions can be made to the method of manufacturing the part 10, the method of preparing the part 10, and the chamber 12, as hereinbefore described, without departing from the field and scope of the present invention.

[0086] Although the present invention has been described with reference to certain specific examples, those skilled in the art will certainly realize many other equivalent forms of the method of manufacturing the component 10, the method of preparing the component 10, and the chamber 12 that incorporate all of the characteristics recited in the claims and the scope of protection defined thereby.

Claims

1. A method for manufacturing a part (10) suitable for installation in a protective chamber (12) of a machine for the production and / or packaging of pharmaceutical products, comprising the steps of: Said protective chamber (12) is a controlled atmosphere chamber, isolated in a sealed manner from the external environment and adapted to receive one or more parts or devices or elements of an instrument (11) formed by one or more parts (10), in a method for making the interior of said protective chamber (12), i.e. the instrument (11) or the parts (10) forming the instrument or element, suitable for a suitable decontamination and sterilization treatment, for example a CIP (cleaning in place) / SIP (sterilization in place) treatment using vaporized hydrogen peroxide (VPHP, vapor phase hydrogen peroxide), comprising: The present invention provides a method for manufacturing a component (10) made of a first material selected from the group consisting of aluminum (Al), magnesium (Mg), titanium (Ti), steel or alloys thereof, composites with a polymer matrix, carbon fiber or combinations thereof, the component (10) being placed in a chamber (12) and comprising at least one coupling portion adapted to be coupled with a corresponding mating coupling portion provided on the other component (10) or on the inner wall (13) of the chamber (12), the component comprising at least one outer surface (18) facing outward in the assembled and installed state of the component, i.e. directly exposed to the air of the chamber (12), and an inner surface (19) that is not placed in contact with the air of the chamber (12) in the assembled and installed state of the component; Prior to assembly or installation of the part (10) in the chamber (12), i.e., prior to its joints being stably joined to corresponding mating joints or to the inner wall (13) of the chamber (12), subjecting the part (10) to a thermal spray treatment with a solid powder of a second material accelerated by a supersonic gas jet, the second material being selected from the group consisting of one or more of stainless steel, cobalt chromium metal alloy, nickel alloy, composite with a polymer matrix, metal-ceramic composite, in order to deposit a coating (20) of the second material only on said outer surface (18) and said joints, so as to make said outer surface (18) and said joints suitable to withstand a decontamination or sterilization treatment. A manufacturing method comprising:

2. The method according to claim 1, The thermal spraying process is Cold spray, in which a solid powder of a second material is accelerated by a supersonic gas jet; At least partially molten particles of the second material are obtained from the combustion of oxygen and fuel. A high velocity oxygen-fuel (H Spray treatment with VOHF coating The manufacturing method is selected from the following:

3. The method according to claim 2, A method of manufacturing comprising spraying a mixture of gases carrying particles of a second material onto an exterior surface (18) at a velocity of between 300 m / s and 1400 m / s, while holding the part (10) in a fixed and stable position at all times by a support suitable for resisting the forces of the gas and particle mixture.

4. The method according to claim 3, A method of manufacturing comprising heating at least a portion of the gas transporting the solid particles to a temperature of about 200°C to 1100°C.

5. The method according to claim 3 or 4, A method of manufacturing wherein the gas transporting the solid particles has a pressure of from 5 bar (500 kPa) to 100 bar (10,000 kPa).

6. The method according to claim 5, A housing sheet (25) is provided at at least one joint configured to receive a sealing element (26), The method further comprises coating the joint with the coating (20) up to the extent of the outer edges (27) of the housing sheets (25).

7. The method according to any one of claims 1 to 6, A manufacturing method in which changes in an exterior surface (18) of a part (10) are tracked by using a spray nozzle (21) mounted on an anthropomorphic arm and / or a numerically controlled machine having at least four axes of actuation.

8. The method according to claim 7, A method of manufacturing comprising positioning the spray nozzle (31) to spray the second material at an angle of incidence (α) comprised between ±45° with respect to a direction perpendicular to the surface to be coated.

9. The method according to claim 7 or 8, A buildup of said second material forms between said outer surface (18) and said joining edge (17). corresponding to the corners (34) to be formed or possible corners of said outer surface (18) If formed corresponding to a depression or protrusion, the method further comprises removing said buildup by a suitable tool immediately after the second material is deposited, substantially continuously during the movement of the spray nozzle (31).

10. A component suitable for installation in a protective chamber (12) of a machine for the production and / or packaging of medicinal products, said component comprising: a first material selected from the group consisting of aluminum (Al), magnesium (Mg), titanium (Ti), steel or alloys thereof, composites with polymer matrices, and carbon fibers; at least one coupling portion configured to be coupled with a corresponding mating coupling portion provided on another part (10) of the protective chamber (12) or on an inner wall (13) of the protective chamber (12); at least one outer surface (18) facing the outside when the components are assembled and installed, i.e. directly exposed to the air of said protective chamber (12) and subjected to a decontamination or sterilization treatment, e.g. CIP (cleaning in place) / SIP (sterilization in place) treatment using vaporized hydrogen peroxide (VPHP, vapor phase hydrogen peroxide), and an inner surface (19) that is not placed in contact with the air of the chamber (12) when the components are assembled and installed, the component includes a coating (20) made of a second material selected from the group consisting of one or more of stainless steel, cobalt chromium metal alloy, nickel alloy, material with a polymer matrix, and metal-ceramic composite material, coating only the exterior surface (18) and the joints to make the exterior surface (18) and the joints suitable to withstand a decontamination or sterilization process; The part, wherein a coating (20) made of a second material is obtained by thermal spraying with a powder accelerated by a supersonic gas jet.

11. 11. The component according to claim 10, fixed column, Drive shaft, Transport wheels for belts, container, cover, Casings for gearboxes and / or motors, Articulated parts of a robot or part of the robot Support elements such as brackets, flanges, fixed or movable arms, Slider, drum, Pulley, Mounting materials such as screws and bolts, A part selected from the group consisting of:

12. A method for conditioning a chamber (12) of a machine for the production and / or packaging of pharmaceutical products, said chamber (12) being a protected chamber with a controlled atmosphere, isolated and separated in a sealed manner from the external environment, and adapted to receive one or more parts, devices or elements of a device (11), comprising: Manufacturing a plurality of components (10) using a manufacturing method according to any one of claims 1 to 9, Assembling or placing the parts (10) at respective locations within the chamber (12) corresponding to respective couplings configured to couple with corresponding mating couplings on another part (10) or on an inner wall (13) of the chamber (12) to form at least one part, or at least one device, or at least one element of the device (11); Placing at least one part of said equipment (11) and / or said at least one device, said at least one element and / or possibly other parts in a predetermined position in said chamber (12), closing said chamber (12) so as to isolate it in a sealed manner from the external environment; A conditioning method for subjecting the interior of the chamber (12), i.e. the equipment (11), devices, elements and possibly other parts (10) previously placed inside the chamber (12), to a decontamination or sterilization treatment, e.g. a CIP (clean in place) / SIP (sterilization in place) treatment, so as to decontaminate and / or sterilize at least the respective outer surfaces (18) of the parts (10) and / or equipment (11), devices or elements previously placed inside the chamber (12).

13. The adjustment method according to claim 12, A method of preparation, wherein the decontamination or sterilization process uses vaporized hydrogen peroxide (VPHP, vapor phase hydrogen peroxide).

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