System for dispensing sterile elements from a sterile storage to an environment for aseptic processes

Abstract

Described is a system (700) for dosing sterile elements (T) from a sterile storage system (112) to an environment (102) designed to contain aseptic processes, particularly for feeding a process chamber (102) for aseptic processes, comprising removable aseptic means for connecting the storage system (112) to the process chamber (102) and a choke valve (125) for regulating the flow of sterile elements (T) during the passage from the storage system (112) to the process chamber (102). The choke valve (125) is designed to pass from an open configuration to a closed configuration, and vice versa, wherein, in the open configuration, the sterile elements (T) pass from the storage system (112) to the process chamber (102), whilst in the closed configuration the transit between the storage system (112) and the process chamber (102) is blocked. The invention also relates to a container (101 ) that can be sterilised by superheated steam, especially for filling and closing sterile elements (T) for parenteral drugs, and a method for feeding sterile elements between two sterile environments (102, 112) designed to be connected to each other, in particular from a sterile storage system (112) which can be removably coupled with a process chamber (102) that can be sterilised by superheated steam.

Description

[0001] System for dispensing sterile elements from a sterile storage to an environment for aseptic processes DESCRIPTION

[0002] Technical field

[0003] This invention relates to a system for dosing sterile elements from a sterile storage system to an environment designed to contain aseptic processes, particularly for feeding a process chamber which can be sterilised with superheated steam, a container which can be sterilised with superheated steam, particularly for filling and closing sterile elements for parenteral drugs, and a method for feeding sterile elements between two sterile environments designed to be connected to each other, in particular from a sterile storage system which can be removably coupled with a process chamber which can be sterilised with superheated steam.

[0004] Background Art

[0005] The process of filling and finishing containers such as bottles, vials, syringes and carpules, known as “fill-finish”, is crucial in the production of drugs, especially for injectable ones. The main challenge is to maintain the sterility of the product during this delicate phase. Unlike terminal sterilisation, where the drug is treated in closed containers, the “aseptic fill-finish” involves the risk of losing sterility, since the drug is dispensed in open containers. For this reason, in order to ensure sterility, it is essential that the filling and finishing are carried out in specially designed environments to prevent contamination.

[0006] The national and international pharmaceutical guidelines establish strict requirements for the qualification and production of machinery used in this process. The production in an aseptic environment requires particular care, and the regulations require monitoring methods to ensure sterility and prevent particle and microbiological contamination during the filling and finishing of the containers.

[0007] The aseptic filling and finishing, known as “fill-finish”, currently occurs inside systems with redistricted access barriers (RABS) or isolators. These apparatuses create a confined environment for the filling and sealing of the containers, often integrating with automatic filling machines. The legislation imposes strict particle and microbiological requirements in these areas, with strict limits for non-viable particles both at rest and during the cycle and requiring a total absence of microbiological contamination.

[0008] The filling machines integrated into RABS or isolators must handle both parts in direct and indirect contact, adopting special measures to prevent contamination of the sterile product. The isolators can be closed or opened, with a mouse-hole for the extraction, designed to minimise the risk of contamination while performing fill-finish processes inside them. They incorporate ventilation chambers with HEPA filtration (high efficiency particulate air system) and HVAC systems (heating, ventilation and air conditioning) to maintain controlled environmental conditions.

[0009] The isolators, which can be likened to small “white rooms”, are constructed with materials certified for aseptic areas, such as stainless steels or plastic, and are subject to a rigorous qualification. The air inside isolators is filtered to reduce the amount and size of the dispersed particulate, and decontamination systems, often based on vaporised hydrogen peroxide, are used before production to reduce microbiological charge. The meticulous design allows for effective cleaning and sanitising.

[0010] The current aseptic filling and finishing process, although advanced, has some critical aspects. The main technique used for reducing the microbiological charge is the hydrogen peroxide or vaporised hydrogen (VPHP or VHP) generator, which is considered essential for achieving the aseptic condition. However, this method is defined as “decontamination” and not “sterilisation” and shows significant limitations with respect to systems such as steam sterilisation, ionizing radiation, or chemical sterilisation with ethylene oxide (ETO).

[0011] The VHP develops a surface action, having a low penetration strongly depends on the previous surface cleaning process and is difficult to control; in fact, even light films of accumulated residual substances can adversely affect the effectiveness of the process. In addition, VHP residues may compromise the pharmaceutical specialty; therefore, adequate removal of any residues from the indirect contact areas must also be ensured. This limitation makes VHP unsuitable for sterilising the parts in direct contact with pharmaceutical products and is commonly only accepted for the indirect contact surfaces in the filling and closing machines. As a result, these parts must be disassembled and steam sterilised separately, resulting in high production times and additional costs.

[0012] The transfer of sterilised parts inside the isolator, normally at a lower sterility level, involves the risk of losing the sterility during contact with air or handling. Complicated and risky methods, such as the use of “Rapid Transfer Port” (RTP) or the transfer and assembly by means of the isolator gloves, are used to maintain sterility, but are subject to residual contact risks, procedural errors and violations of the “first air” criterion in the aseptic area.

[0013] The situation becomes particularly critical for large components, such as vibrating cups and hoppers, which are sterilised in autoclaves, but because of the size they cannot be handled with gloves with the doors closed, thereby compromising the sterile safety. In conclusion, the current system represents a mitigated risk but not completely safe from the point of view of sterility.

[0014] Italian patent application No. 102023000024198, filed in the name of the same Applicant, describes a double-container system, both of which can be sterilised by superheated steam, which - by means of an automatic and autonomous process for sterilising the process instruments - greatly limits or eliminates the need for intervention by the operator during normal operation of the system, without a supporting autoclave or gloves, since there are no preparation operations in an aseptic condition.

[0015] Moreover, the above-mentioned system can be cleaned automatically, like conventional systems, such as freeze-dried devices, and guarantees an absolute safety of the sterility of the machine and all its parts inside the process chambers, making the filling and finishing step of the bottles, syringes and carpules extremely efficient, so much so that it is possible to achieve production speeds equal to the conventional filling systems.

[0016] However, a crucial problem relates to the feeding of the sterile elements which serve as the closing or covering of vials, bottles or syringes.

[0017] In fact, the sterile elements are contained in portable storage units which, although internally sterilised, can also be handled in non-sterile environments.

[0018] When the operator connects these storage units with the sterilised environment which has been created, it is expected that aseptic continuity is ensured.

[0019] Similarly, the disconnection of the sterile storage system must not adversely affect the aseptic properties of the internal environment of the containers sterilised by superheated steam or sanitised with VHP and, obviously, not even of the inside of the storage system itself.

[0020] Summary of the Invention

[0021] The aim of the invention is to provide a dosing system which guarantees a flow of sterile elements from one environment (sterile) to another, without adversely affecting the sterility.

[0022] In the context of the above-mentioned aim, another aim of the invention is to provide a method for feeding sterile elements between two sterile environments which is practical and fast to use, in such a way as to minimise the production and maintenance costs.

[0023] Another aim of the dosing system according to the invention is to be economically competitive with respect to similar apparatuses on the market. This purpose, as well as these and other aims, which are described in more detail below, are achieved by a system, according to the invention, comprising the technical features described in one or more of the appended claims. The dependent claims correspond to possible different embodiments of the invention.

[0024] In particular, according to a first aspect, this invention relates to a system for dosing sterile elements from a sterile storage system to an environment suitable for aseptic processes, that is to say, designed to contain aseptic processes, in particular for feeding a process chamber, designed to contain aseptic processes, with the sterile elements coming from a sterile storage system inside it and controlled in a non-sterile environment (white chamber). The process chamber can preferably be sterilised with superheated steam. The system according to the invention comprises aseptic connection means between the above-mentioned sterile storage system and the process chamber, as well as including a choke valve for regulating the flow of the sterile elements entering towards the process chamber from the sterile storage system.

[0025] Advantageously, the aseptic connection means are removable and therefore allow the storage system to be coupled to and uncoupled from the process chamber, guaranteeing the sterility and aseptic nature of their respective inner parts both when storage system and process chamber are coupled and when they are uncoupled.

[0026] The choke valve is designed to regulate the flow of sterile elements during the passage from the storage system to the process chamber, passing between an open configuration, in which the sterile elements can pass from the storage system to the process chamber, and a closed configuration, in which the transit between the storage system and the process chamber is blocked.

[0027] Advantageously, there is a central unit for controlling the opening and closing of the choke valve, in such a way as to automate the dosing.

[0028] The Applicant has devised these aseptic connection means by mounting two portions of aseptic connection device which can be coupled to each other: a first portion of the aseptic connection device mounted at the outlet of the storage system and a second portion of the same device at the inlet of the process chamber.

[0029] Moreover, the Applicant has perceived that by exploiting gravity to obtain the flow of sterile elements, the system would benefit in economic terms, rather than installing costly and complicated suction systems, vibrating means or other apparatuses.

[0030] For that purpose, the outlet of the storage system has been positioned above the inlet of the process chamber, in such a way that the flow of sterile elements is achieved by gravity.

[0031] In other words, in the open configuration of the choke valve, the passage of the sterile elements occurs by gravity, since the storage system is, at least partly, above the process chamber.

[0032] Another aspect of the invention relates to a container which can be sterilised by superheated steam or sanitised with VHP, particularly for filling and closing sterile elements for parenteral drugs, comprising, on a load-bearing frame, a chamber for processing the sterile elements designed to be removably connected to a sterile storage system and the system for dosing the flow of sterile elements, coming from the sterile storage system and entering the process chamber, which is the object of the invention.

[0033] Advantageously, the process chamber is designed to be alternatively connected to the storage system or to a vaporisation duct for the sterilising with superheated steam or sanitising with VHP of the inner parts of the container, so as to sterilise the inner parts of the container and of the process chamber, before its coupling with the sterile storage system.

[0034] Moreover, protection is required for a method for feeding sterile elements in transit between two sterile environments designed to be connected to each other, in particular from a sterile storage system which can be removably coupled with a process chamber which can be sterilised with superheated steam or sanitised with VHP.

[0035] The method mentioned above firstly comprises placing the sterile elements inside the sterile storage system, or another sterile environment, removably and aseptically connectable to an environment designed to contain aseptic processes, such as a process chamber, preferably already in an aseptic condition. The outlet of the storage system is then put in communication with the inlet of the process chamber, in such a way as to create a flow of the sterile elements for passage from the sterile storage system to the process chamber.

[0036] This connection is achieved by coupling two portions of an aseptic connecting device mounted at the outlet of the storage system and at the inlet of the process chamber.

[0037] The choke valve of the system for dosing the sterile elements according to the invention is actuated, in such a way that the sterile elements, falling from the storage system towards the process chamber, are filtered by the choke valve which can pass from the open configuration to the closed configuration, and vice versa, following a command issued in the central unit. The flow of sterile elements is controlled by the choke valve and they are selectively passed from the storage system to the process chamber according to the frequency of the program entered in the central unit.

[0038] Detailed description

[0039] Further features and advantages of the invention are more apparent in the detailed description below, with reference to a preferred, non-limiting embodiment of the dosing system, illustrated by way of example and without limiting the scope of the invention, with the aid of the accompanying drawings, in which:

[0040] Figure 1 shows the system 700 installed in a container 101 which can be sterilised by superheated steam, for dispensing sterile caps T

[0041] Figure 2 shows the container 101 of Figure 1 with the aseptic connection device 107 and the vaporisation duct 120 connected by means of the relative half-valve 120a coupled to the second portion 107b of the device 107.

[0042] The accompanying drawings show a preferred embodiment of a system 700 for dosing sterile elements T, for example caps for bottles from a sterile storage system 1 12 to a process chamber 102 which can be sterilised with superheated steam.

[0043] The system 700 comprises a first portion 107a and a second portion 107b of an aseptic connection device 107, which can be removably coupled to each other and which are mounted, respectively, at the outlet 1 12a of the storage system 1 12 and at the inlet 102b of the process chamber 102.

[0044] There is also a choke valve 125, rotatable about an axis of rotation Y, for regulating the flow of the caps T during the passage from the storage system 112 to the process chamber 102. The choke valve 125 is designed to pass from an open configuration, in which the flow of the caps T is allowed from the storage system 1 12 to the process chamber 102, to a closed configuration, where the flow is blocked, and vice versa.

[0045] In other words, the aseptic connecting device 107 is achieved by coupling the first portion 107a with the second portion 107b and, once the two portions 107a and 107b are coupled, it is positioned upstream of the choke valve 125 relative to the flow of the sterile elements T.

[0046] This coupling is achieved, for example, by means of clamping the device 107, of per se known type, for manual use.

[0047] A central unit (not illustrated) for controlling the opening and closing of the choke valve, controls and manages the frequency of feeding the caps T in a process chamber 102.

[0048] With reference to Figure 1 , the outlet 1 12a of the storage system 1 12 is positioned above the inlet 102b of the process chamber 102, in such a way that the flow of the caps T is achieved by gravity.

[0049] In practice, the flow of the sterile elements T is achieved by gravity and is in this case substantially normal relative to the ground and the axis of rotation Y is substantially normal relative to the direction of flow of the sterile elements T.

[0050] The greater efficiency of the gravity is given when the flow of the sterile elements T is perpendicular to the ground, that is to say, it has a vertical direction Z normal to the ground.

[0051] According to the embodiment described here, the choke valve 125 is actuated by a rotary butterfly 125a which, controlled by the central unit, regulates the opening and closing of the choke valve 125.

[0052] More in detail, the choke valve 125 has a central pivot 125c designed to be rotated about the axis of rotation Y and a series of blades 125p symmetrically protruding from the pivot 125c.

[0053] With reference to Figure 2, the container 101 which can be sterilised by superheated steam for filling and closing the sterile elements T (caps T for closing bottles for parenteral drugs) comprises, on a load-bearing frame 1 15, a process chamber 102 of the caps T designed to be removably connected to a sterile storage system 1 12.

[0054] According to this example, the process chamber 102 is designed to be connected to the storage system 1 12 or, alternatively, to a vaporisation duct 120 which introduces the superheated steam for sterilising the process chamber 102 and the internal parts of the container 1 (Figure 2).

[0055] For convenience, Figure 2 illustrates a system wherein the storage system 1 12 is disengaged and the vaporisation duct 120 is coupled to the process chamber 102.

[0056] For that purpose, the vaporisation duct 120 is coupled to the system 700 by a relative half-valve 120a which can be coupled to the 107b of the device 107.

[0057] The choke valve 125 is also positioned on the end portion of the neck 102a. The process chamber 102 is for containing the sterilised caps T and is connected to another environment for aseptic processes (not illustrated) where the process for filling and finishing the bottles is performed, known as “fill-finish”, which are closed at the top by the caps T.

[0058] As stated, since the storage system 1 12 is located above the process chamber 102, the caps T enter into the process chamber 102, through the neck 102a, by gravity.

[0059] In order to dose the requirement of caps T, which depends on the filling and finishing speed of the bottles, the choke valve 125 is used, which is also mounted on the neck 102a.

[0060] As shown in Figure 1 , the choke valve 125 comprises a central pivot 125c, which can rotate about the axis of rotation Y. A series of blades 125p extend from the pivot 125c, symmetrically projecting from the pivot 125c. For example, there are four blades 125p, positioned at right angles to each other.

[0061] The feeding of the process chamber 102 with the sterile caps T coming from the sterile storage system 1 12, which can be removably coupled with the process chamber 102 and designed to be also controlled in a non-sterile environment, comprises firstly collecting the sterile elements T inside the storage system 1 12 and connecting the storage system 1 12 with the process chamber 102, which has already been made suitable for aseptic processes by the introduction of superheated vapour or sanitising with VHP. This connection is achieved by coupling the outlet 1 12a of the storage system 112 to the inlet 102b of the process chamber 102, in such a way as to form a flow of the sterile elements T for passage from the storage system 1 12 to the environment to the process chamber 102. The choke valve 125 of the system 700 for dosing the sterile elements T is actuated: the choke valve 125 is passed from the open configuration to the closed configuration, and vice versa, depending on the set up the central unit which controls and manages the flow of sterile elements T from the storage system 1 12 to the process chamber 102.

[0062] From the above description it may be seen how the invention achieves the preset purpose and aims and in particular the fact that a dosing system is made which guarantees the sterility of the sterile elements flowing from a sterile environment to another environment suitable for aseptic processes, that is to say, which is also designed to contain aseptic processes. in particular, the aseptic connection device used guarantees that the sterile caps remain sterile, both inside the process chamber and inside the sterile storage system, even after the storage system is uncoupled from the process chamber.

[0063] Another advantage of the invention is that it has achieved a method for feeding sterile elements between two sterile environments which is extremely easy to use, even manually, and does not require lengthy times. Lastly, the use of gravity to create the flow of sterile elements between the two environments to be connected, instead of the use of suction devices, screw feeders or other electro-mechanical means, simplifies the making of the container and reduces the maintenance costs, making the container and the dosing system economically advantageous. The invention described can be modified and adapted in several ways without thereby departing from the scope of the inventive concept.

[0064] Moreover, all the details of the invention may be substituted by other technically equivalent elements.

[0065] In practice, the materials used, as well as the dimensions, may be of any type, depending on requirements, provided that they are consistent with their production purposes.

Claims

CLAIMS1 ) A system (700) for dosing sterile elements (T) from a sterile storage system (1 12) to an environment (102) suitable for containing aseptic processes, particularly for feeding a process chamber (102), comprising: removable aseptic means for connecting the storage system (1 12) to the process chamber (102); a choke valve (125) for regulating the flow of sterile elements (T) during the passage from the storage system (1 12) to the process chamber (102); the choke valve (125) being suitable for passing from an open configuration to a closed configuration, and vice versa; wherein, in the open configuration, the sterile elements (T) transit from the storage system (1 12) to the process chamber (102); while in the closed configuration the transit between the storage system (1 12) and the process chamber (102) is blocked.2) The system (700) according to claim 1 , wherein the aseptic connection means comprise a first portion (107a) and a second portion (107b) of an aseptic connection device (107), mutually coupled, mounted respectively at the outlet (1 12a) of the storage system (1 12) and at the inlet (102b) of the process chamber (102).3) The system (700) according to claim 2, wherein the outlet (1 12a) of the storage system (1 12) is positioned above the inlet (102b) of the process chamber (102), in such a way that the flow of the sterile elements (T) is achieved by gravity.4) The system (700) according to any one of claims 1 to 3, wherein the choke valve (125) is suitable for being rotated about an axis of rotation (Y), for the distribution of the sterile elements (T) from the storage system (1 12) to the process chamber (102); the axis of rotation (Y) being substantially normal relative to the direction of flow of the sterile elements (T).5) The system (700) according to claim 4, wherein the choke valve (125) is driven by a rotary butterfly (125a) which regulates the opening and closingof the choke valve (125); the rotary butterfly (125a) being suitable to be controlled by a central unit.6) The system (700) according to claim 5, wherein the rotary butterfly (125a) is suitable for being programmed in such a way that the sterile elements (T) falling from the storage system (1 12) towards the process chamber (102) are filtered by the passage of the choke valve (1 12) from the open configuration to the closed configuration, and vice versa.7) The system (700) according to claim 5, wherein the central unit controls the passage of the choke valve (1 12) from the open configuration to the closed configuration, and vice versa, in such a way as to obtain a controlled flow of the sterile elements (T) from the storage system (1 12) to the process chamber (102) according to the frequency provided by the program inserted in the central unit.8) The system (700) according to any one of claims 1 to 7, wherein the choke valve (125) comprises a central pivot (125c) suitable for being rotated about the axis of rotation (Y) and a series of blades (125p) symmetrically protruding from the pivot (125c).9) The system (700) according to any one of claims 1 to 8, wherein the aseptic connecting device (107), achieved with the mutual coupling of the first portion (107a) with the second portion (107b), is positioned upstream of the choke valve (125) relative to the flow of the sterile elements (T).10) A container (101 ) which can be sterilised by superheated steam, particularly for the filling and the closing of sterile elements (T) for parenteral drugs, comprising, on a load-bearing frame (1 15): a process chamber (102) for the sterile elements (T) suitable for being removably connected to a sterile storage system (1 12); a system (700) for dosing the flow of sterile elements (T), coming from the storage system (1 12) and entering the process chamber (102), according to any one of claims 1 to 7.1 1 ) The container (101 ) according to claim 10, wherein the process chamber (102) is suitable for being selectively connected to the storagesystem (1 12) and to a vaporisation duct (120) for the superheated steam sterilisation of the internal parts of the container (101 ).12) A method for feeding sterile elements between two sterile environments (102, 112) suitable for being connected to each other, in particular from a sterile storage system (1 12) which can be removably coupled with a process chamber (102) suitable for containing aseptic processes, comprising the following steps:- collecting the sterile elements (T) in a sterile storage system (1 12) suitable for being removably and aseptically connected to an environment (102) suitable for containing aseptic processes,- putting in communication the outlet (112a) of the storage system (1 12) with the inlet (102b) of the environment (102), in such a way as to form a flow of the sterile elements (T) passing from the storage system (1 12) to the environment (102),- actuating a choke valve (125) of a system (700) for dosing the sterile elements (T) according to any one of claims 1 to 7; the choke valve (125) being suitable for passing from an open configuration to a closed configuration, and vice versa, as controlled by a central control and management unit for respectively allowing or selectively blocking the passage of the passage of sterile elements (T) from the storage system (1 12) to the environment (102), depending on the frequency provided by said central unit.

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