EP3681635A1

EP3681635A1 - Transportable clean room, method for producing a transportable clean room, and method for filling a medicine container in a transportable clean room

Info

Publication number: EP3681635A1
Application number: EP18773123.7A
Authority: EP
Inventors: Stefan Mossig
Original assignee: Vetter Pharma Fertigung GmbH and Co KG
Current assignee: Vetter Pharma Fertigung GmbH and Co KG
Priority date: 2017-09-14
Filing date: 2018-09-14
Publication date: 2020-07-22
Also published as: RU2020113347A; RU2764772C2; US12070742B2; JP2020533169A; JP7420709B2; MX2020002728A; JP2023088999A; US20200261901A1; JP7550261B2; CA3075445A1; WO2019053186A1; DE102017216366A1; BR112020004694A2; RU2020113347A3

Abstract

The invention relates to a transportable clean room (1) for filling at least one medicine container (9), located in the clean room (1), with at least one active substance, wherein: the clean room (1) is enclosed in an air-tight manner by an at least partially flexible shell (3); the shell (3) has at least one active substance connection region (5) which can be opened; and a manipulation device (11) and at least one medicine container (9) are located in the clean room (1). According to the invention, the shell (3) has at least one actuation connection region (23), wherein the manipulation device (11) has at least one filling device (13) which can be coupled to the active substance connection region (5) for introducing at least one active substance into the at least one medicine container (9) located in the clean room (1), and the manipulation device (11) can be actuated by means of an actuation device (25) via the actuation connection region (23) of the shell (3), and is designed to displace the filling device (13) - relative to the at least one medicine container (9) - and/or to actuate the filling device (13).

Description

DESCRIPTION

Transportable clean room, process for producing a transportable clean room and method for filling a medicine container in a transportable clean room

The invention relates to a transportable clean room for filling at least one arranged in the clean room drug container with at least one active ingredient, a method for producing such a portable clean room and a method for filling a drug container in such a portable clean room.

Transportable clean rooms of the type mentioned here are known. Typically, a transparent shell of the transportable clean room is clamped by means of a flexible or rigid outer support structure. About a closable opening of the shell and / or a lock drug container, agents, filling devices and / or closing devices in the clean room can be introduced. By means of trained in the shell intervention gloves and introduced into the clean room filling and / or closing a human manipulator can fill and / or close the drug container. However, such clean rooms are only manual and therefore expensive to operate. In addition, to be filled drug containers must be introduced into such clean rooms after clamping the clean room, so that the risk of contamination of the clean room is high. Also, the active agent to be filled must be introduced through the opening or the lock, which is typically so large that the human manipulator can reach through it to arrange the drug container or the drug in the clean room or to remove from the clean room. Thus, the risk of contamination is particularly high, especially if the clean room is used in a non-sterile environment.

The object of the invention is to provide a transportable clean room, a method for producing such a portable clean room and a method for filling a medicament container in such a portable clean room, wherein said disadvantages are avoided. The object is achieved by providing the subject matters of the independent claims. Advantageous embodiments emerge from the subclaims.

The object is achieved, in particular, by providing a transportable clean room for filling at least one medicament container arranged in the clean room with at least one active ingredient, wherein the clean room is enclosed airtightly by an at least partially flexible envelope. It is provided that the shell has at least one disclosed active substance connection region and at least one actuating connection region, in particular a robot connection region, wherein a manipulation device and at least one medicament container are arranged in the clean room. The disclosed active substance connection region is preferably designed such that at least one active substance can be introduced from outside the clean room into the clean room via the active substance connection region, which is sealed in particular in a sterile manner to an external environment. In addition, the manipulation device has at least one filling device which can be coupled to the active substance connection region and is preferably coupled to the latter for introducing the at least one active substance into the at least one medicament container arranged in the clean room, wherein the manipulation device via the actuating connection region by means of a particularly external actuating device, in particular a robot. in particular, the robot connection area, the shell operable, and for the displacement of the filling device - is arranged relative to the at least one medicament container - and / or for actuating the filling device. By means of such a transportable clean room, the automation of the filling of medicine containers with at least one active ingredient is increased and thus particularly efficient. Thus, drug containers can be filled quickly and inexpensively, the risk of contamination is reduced by the complete and also during the filling of the drug container existing seal to the outside. Preferably, the manipulation device itself, particularly preferably together with the filling device, is displaceable by means of the preferably automated actuating device, in particular of the robot. Alternatively or additionally, the manipulation device is at least partially automated, particularly preferably fully automated, so that the displacement and / or the actuation of the filling device can be carried out automatically. For automated actuation of the manipulation device, in particular a robot arm of a robot is provided, which is set up after coupling with the manipulation device for displacing the manipulation device. For automated actuation of the filling device the actuating connection region preferably has at least one signal transmission element, in particular signal cable and / or signal cable connection, for the transmission of, in particular, electrical, hydraulic and / or pneumatic signals. The at least one signal transmission element is set up to forward a signal supplied by the actuating device to the in particular automated filling device. Thus, the automation of the filling - especially when the manipulation device is actuated by means of the robot - is very high and the filling can be performed efficiently.

The clean room is preferably portable so that it is portable by a human. The clean room thus preferably has a weight and volume that is portable for a human. Particularly preferably, the weight is less than 100, preferably less than 10 kg and the volume of the clean room is less than 4 m ³ , preferably less than 2 m ³ , preferably less than 1 m ³ , preferably less than 0.5 m ³ , preferably less as 0.15 m ³ , preferably less than 0.03 m ³ .

Preferably, the shell of the clean room has no passage, in particular no door, for entering and / or leaving the clean room by a human. Thus, the clean room is not accessible. An action on the interior of the clean room, in particular a mechanical manipulation of the medicament container and / or actuation of a device arranged in the clean room, is preferably exclusively via connection areas, in particular the active substance and / or actuation connection area, and / or the at least partially flexible enclosure, in particular the flexible part of the envelope, more particularly a part of the envelope designed for manual intervention with the interior of the clean room, and / or a passage in the envelope.

A medicament container is understood here to mean in particular an ampoule, a vial, a vial, a syringe or a carpule. Preferably, a plurality of such medicament containers are arranged in the clean room. Particularly preferred is a small number of drug containers, especially for use in personalized medicine, arranged in the clean room. Thus, it is possible to fill the small number of drug containers customized for a patient. Alternatively, it is provided that a large number of medicament containers, in particular for use in the mass market, is arranged in the clean room. Preferably, the medicament container is at least partially prefilled with a substance, in particular an additional medical auxiliary and / or active ingredient. The substance preferably has a high durability, at least in the purity class present in the clean room, so that it can be stored for a plurality of days, weeks, months and / or years in the drug container in the clean room without the durability being endangered , in particular, without exceeding a best before date and / or an expiration date of the substance. The substance is preferably provided for mixing with the active ingredient, whereby a specific medical effect is achieved. Preferably, the substance is arranged in a first chamber of the medicament container, wherein the first chamber is closable by means of a closure element at least during storage and / or transport of the clean room. Preferably, the closure element is detachably mounted, so that before filling the medicament container, the first chamber is opened by removing the closure element, in particular by means of the manipulation device and the first chamber can be filled by means of the filling device, wherein the substance is mixed with the active ingredient. Thus, a VorbefüUung with the substance take place temporally and / or spatially separated from the filling with the drug, the at least one prefilled drug container in the clean room long, especially several days, weeks, months or years long, stored and transported with little effort can. The VorbefüUung with the substance in the production of the clean room, especially in a clean environment, especially a stationary clean room, performed. The filling with the active ingredient is carried out at a later time in the finished clean room, preferably in an impure environment. Since the provision of clean environment is expensive and associated with high costs, the cost of filling the particular partially pre-filled drug container with the drug in an impure environment are reduced.

Preferably, the medicament container is designed as a multi-chamber system, in particular a dual-chamber system, wherein the substance is arranged in the first chamber and a second chamber of the medicament container is adapted for filling with the active ingredient by means of the filling device. The closure element is in this case preferably designed as a displaceable separating element, which fluidly separates the first chamber from the second chamber, wherein a fluidic connection between the chambers by moving the separating element via a bypass is possible. In addition, preferably, a further closure element for closing the second chamber provided, which is also detachably mounted such that it can be removed preferably before the filling of the second chamber by means of the manipulation device. Such multi-chamber systems are already known, so that at this point not further discussed on their operation. An actuating device is understood to mean, in particular, a partially automated or fully automated actuating device, in particular a robot. The actuating device is set up to actuate the manipulation device mechanically and / or electrically. The actuating device is preferably designed to carry out a repetitive, in particular regular, movement, in particular of an actuating arm, in particular of a working or robotic arm, in order to actuate, in particular displace, the manipulating device. Alternatively or additionally, the actuating device is set up to emit at least one electrical signal, preferably a regular sequence of electrical signals, to the manipulation device in order to actuate the manipulation device in such a way that it performs a mechanical movement and / or transmits an electrical signal.

An actuating connection region is understood here to mean, in particular, a connection region for the in particular automated actuating device. In particular, an actuating connection region is understood as a robot connection region.

The sheath is preferably flexible enough to be collapsible. More preferably, the clean room is enclosed airtight by the shell, that the shell is inflatable and / or evacuated. It is therefore preferably possible for the clean room to be subjected to a vacuum such that the shell collapses. This reduces the need for storage space for such clean rooms.

Particularly preferably, the clean room is provided for transport and / or storage, in particular for long, especially several years of storage, in a non-sterile, especially impure environment. During such storage, the purity of the clean room is not reduced because the shell encloses the clean room airtight. Alternatively or additionally, the clean room for use, in particular for the filling of the medicament container, provided in a non-sterile environment. Thus, it is possible to decouple the production of the clean room, the storage of the clean room, the transport of the clean room and the filling of the drug container in the clean room in time and / or locally, without the costs being high, since a clean environment is not required for all steps. In particular, the storage and transport of such a clean room can take place without endangering the purity of the interior of the clean room in an impure environment. Such a clean room can therefore be produced in a clean environment in a first step, then stored and / or transported in a second step, especially over a long time in an impure environment, until finally in a third step the drug container is filled in the clean room can. During the third step, the clean room is preferably arranged in a clean environment. During the second step, the clean room is preferably arranged in an impure environment. Thus, the costs of storage and / or transportation, and thus the total cost of the first step, the second step and the third step - both in a spatial separation and a temporal separation of the first step from the third step - are low. In addition, a process chain that includes all three steps is flexibly adaptable. In particular, the production of the clean room, in particular in large quantities at a central production site and - after transport to a filler - the filling of the drug container in particular a small number of clean rooms, especially a single clean room, be performed at a decentralized filling at the filler.

A clean environment is understood here to mean, in particular, an environment to which purity requirements are placed. Such purity requirements include, in particular, limit values for particle size distributions and / or germ counts, the limit values typically being specified by a purity classification, such as, for example, the EU GMP classification or DIN EN ISO 14644-1. An impure environment is understood here to mean in particular an environment to which no purity requirements are made. Although it is possible that even an impure environment meets the limits of a purity classification, but the compliance of these limits in the impure environment is not required. In particular, no provision is made in an impure environment to comply with these limits.

Preferably, the shell of the clean room has no opening, in particular no closable opening, through which the at least one medicament container or a further medicament container and / or tools can be introduced into the clean room. Particularly preferably, the shell has no closable opening through which a human Manipulator can pass through manually. Alternatively or additionally, the clean room has no lock. This increases the safety of the clean room and reduces the risk of contamination.

Preferably, the clean room has at least one active substance line, in particular active substance tube, for the fluidic conduction of the active substance from the active ingredient connection area to the filling device, wherein the active substance line is preferably flexible and / or foldable. The active substance line is preferably designed as an internal active substance line, which fluidly connects the active substance connection region with the filling device and is arranged in the interior of the clean room. In addition, the active substance connection area is particularly preferably set up in order to be fluidly connected by means of an externally formed active substance line to an external active ingredient supply device, which preferably holds a quantity of active substance required for the filling of a multiplicity of medicament containers. In the connected state, the active substance supply device is preferably set up in order to provide the active substance in particular by means of a drug pump and / or to convey it to the filling device. In particular, in an automated training of the manipulation device thereby a very efficient filling of the medicament container is possible.

Preferably, the active substance connection region is designed as a coupling element, which in the direction of an inner connection region for tensile and / or pressure-resistant coupling with the internal active substance line and / or in the outward direction an external connection region for coupling in particular tensile and / or pressure-resistant coupling with the external active substance line has, wherein the internal and the external active substance line are preferably formed separately from each other. The coupling is - at least in the direction inwards or outwards, in particular in the direction of the fluidic connection - preferably designed as a form-fitting coupling, in particular as a screw and / or detent coupling. Alternatively, the active agent connection region is integrally connected to the active substance line, in particular integrally formed therewith. It is thus avoided that the active ingredient line dissolves in particular in the direction inwards or outwards when the casing is displaced in the region of the active substance connection region and / or when a tensile and / or compressive force acts.

Alternatively or additionally, the clean room, in particular the active substance connection area and / or the at least one active substance line, especially the internal active substance line and / or the external active substance line, at least one active substance valve, which is particularly preferably actuatable automatically, in particular by means of the manipulation device and / or the active substance supply device and when actuated, the fluidic connection, in particular between filling device and active substance connection area and / or between active substance connection area and external active substance supply and / or between filling device and active ingredient supply, releases and / or blocks. Thus, a very secure and in particular automated drug supply and supply is ensured.

The clean room is sealed by the shell completely and also during the filling of the drug container permanently and persistently against an external environment of the clean room sterile. In this case, the active substance connection region is designed such that it is airtight in its closed state and therefore sealed in a sterile manner, and in its opened state, in particular connected to an outer active substance connection and to the filling device, in such a way that it supplies the at least one active substance allowed into the clean room, but at the same time this still airtight and sterile seals to the outside. The active substance connection region thus represents, in particular, a sterile passage for introducing the active substance into the interior of the clean room. The at least one actuating connection region, in particular the robot connection region, is configured in such a way that the manipulation device via the actuating connection region with at least one external actuating device, in particular a robot is arranged outside of the clean room, coupled, that the interior of the clean room remains sterile and airtight sealed to the exterior, so an external environment of the clean room. The actuating connection area represents, in particular, an airtight, sterile mechanism passage to the exterior of the clean room, which is set up for coupling the external actuating device. Under a displacement of the filling device - relative to the at least one medicament container - is understood here a displacement in the clean room, which causes the filling device is displaced into a suitable position for filling the medicament container. The filling device, which preferably has a filling needle, is preferably displaceable directly over the medicament container. Particularly preferably, the filling needle penetrates into an interior of the medicament container in order to fill it.

Preferably, the clean room is set up, in particular for filling the at least one medicine container - at least after the active ingredient connection area with the in particular external active substance supply is connected and / or the actuating connection region is coupled to the actuating device - to be operated completely automatically.

According to a development of the invention, it is provided that the manipulation device has at least one closing device, in particular a stopper setting device, especially a stopper pin, for closing the at least one medicine container with at least one closure arranged in the clean room, in particular for placing the at least one closure arranged in the clean room on the at least one medicament container, and to relocate the closing device - relative to the at least one medicament container - and / or is set up to actuate the closing device. Under a closure is here a particular insertable into the drug container plug, a septum or attachable from the outside closure, in particular a cap or a lid understood. Thus, the risk of contamination of the clean room, which consists in particular when introducing a closure in a classic clean room, reduced because the closure is already - especially from the beginning - in the clean room available. The manipulation device thus has the filling device and the closing device, so that the medicament container in the clean room can be filled and closed.

Alternatively, it is provided that a second manipulation device has the closing device and is set up for displacing the closing device and / or for actuating the closing device. The second manipulation device is also actuable by means of an actuating device, in particular a robot, the at least one actuator.

According to one embodiment of the invention, it is provided that in the clean room, a supply device is arranged, which at least one medicament container for filling by means of the filling device and / or closing with the at least one closure, and / or the at least one closure for closing the medicament container by means the closing device provides. The supply device preferably has a first receiving device, in particular a trough, for receiving the medicament container and / or a second receiving device for the closure and / or a holding device, in particular a plate system, especially a turntable system. Preferably, the at least a medicament container receiving, first receiving device of a semipermeable membrane such closable that a sterilization of the drug container through the semipermeable membrane through is indeed possible, contamination of the drug container with particles and / or germs through the semipermeable membrane is, however, avoided. The first and / or the second receiving device are preferably held by the holding device, wherein the first receiving device is preferably held by a first support element, in particular for supporting the trough, and / or the second receiving device, preferably by a second support element, wherein the first support element and / or the second support element are preferably formed as a plate. Preferably, the first support element and / or the first receiving device and / or the second support member and / or the second receiving device - at least relative to a rotation axis of the providing device - translationally and / or rotationally displaceable, in particular rotatable and / or pivotable. The first support element and / or the first receiving device thus serve to provide the at least one medicament container, and the second support element and / or the second receiving device serve to provide the at least one closure. Particularly preferably, the second receiving device as a closure matrix, in particular plug matrix, for providing and receiving the at least one closure, in particular plug, formed, in which case preferably no second support member is provided. Thus, the automation and the efficiency of the filling are increased and the costs are reduced.

According to one embodiment of the invention, it is provided that the at least partially flexible shell airtightly encloses a first volume in a first functional state of the clean room, wherein it encloses a second volume airtight in a second functional state of the clean room, wherein the second volume is greater than the first volume and is so large that the at least one drug container can be filled by means of the filling device. In the first functional state of the clean room, the shell is preferably compact, collapsed and / or folded. Preferably, the clean room is in the first functional state with a low pressure, in particular a negative pressure, - relative to an environment surrounding the clean room - acted upon. The first volume is preferably less than 1 m ³ , preferably less than 0.15 m ³ , preferably less than 0.03 m ³ . In the second functional state of the clean room, the clean room is preferably subjected to a higher pressure than in the first functional state. In particular, he is with a slight overpressure relative to the exposed to external environment. The second volume is preferably less than 4 m ³ , preferably less than 2 m ³ , preferably less than 1 m ³ , preferably less than 0.5 m ³ . In addition, in the second functional state of the clean room, the envelope is at least partially movable, preferably at least in the area of the actuating connection area, in such a way that the filling device and / or the closing device and / or the manipulation device can be displaced. This is especially true when the filling device and / or the closing device are firmly connected to the manipulation device, wherein the manipulation device is in turn fixedly attached to the sheath.

According to a development of the invention, it is provided that the casing has at least one air connection region, preferably an open and / or closable sterile air connection region. The air connection region preferably also has an air filter. Particularly preferably, this air connection region is set up to supply air to the clean room and / or to remove air from the clean room and / or to move the clean room from the first functional state into the second functional state and / or from the second functional state into the first functional state. Thus, the safety of the clean room is improved, in particular dangerous substances from the clean room - especially in the case of a leak - can not escape.

The clean room preferably has an air line, in particular an air hose, for the fluidic conduction of air, in particular sterile air, from the air connection area into the interior of the clean room, the air line preferably being flexible and / or foldable. The air line is designed as an inner air line and / or as an outer air line, wherein by means of the outer air line of the air connection area with a particular automated air supply device, in particular a pump, can be coupled. Thus, a particularly automated air supply system is provided to supply air into the clean room and / or remove it from the clean room. Alternatively or additionally, at least one air valve is arranged in the air connection region and / or in the air line, which can be actuated by means of the air supply device and / or the manipulation device and, when actuated, the connection between the interior of the clean room and the air connection region and / or between the air connection region and the Air supply device locks and / or releases. Particularly preferably, the air line has a further air filter. Thus, the safety of the clean room and the purity of the clean room are high. Alternatively or additionally, the at least one air connection region is configured to ensure a laminar air flow in the clean room. For this purpose, preferably a first plurality of in particular uniformly distributed air connection areas, in particular on the upper side, are arranged in the envelope, in order, for example, preferably to supply air into the clean room from above. Particularly preferably, a second, corresponding plurality of in particular uniformly distributed air connection areas is arranged in the shell on the underside, which preferably discharges the air homogeneously, in particular downwards, out of the clean room. Thus, a first plurality of air connection regions and a second plurality of air connection regions are provided, which are preferably arranged opposite each other in the shell of the clean room and - at least in the second functional state - are arranged to provide a laminar air flow, in particular from top to bottom.

Preferably, the air connection area is also adapted to pressurize the clean room with an overpressure. Thus, the purity and / or sterility in the clean room is increased and reduces the risk of contamination of the drug container and in particular the active ingredient. Alternatively, the air connection area is set up to pressurize the clean room with a negative pressure. Thus, the safety of the clean room is improved so that in particular dangerous substances from the clean room - especially in the case of a leak - can not escape.

The air connection area is likewise designed such that the interior of the clean room is also sealed off in a sterile manner in the area of the closed or opened air connection area. The air connection region thus represents, in particular, a sterile sealable passage for the supply and / or removal of air, in particular sterile air. "Sterile air" is understood to mean not necessarily, but at least sterilized ambient air in a conventional composition other sterile gases suitable for use in the clean room include, for example, sterile inert gases, noble gases, carbon dioxide, nitrogen, or the like.

According to one embodiment of the invention it is provided that the shell is at least partially transparent. Preferably, the shell has a - preferably transparent - plastic or consists of such a plastic. Thus, optical control through the envelope is possible. In addition, such a clean room is particularly well as a disposable clean room, which after use, so after filling the drug container with the active ingredient and / or after closing the Drug can be disposed of without the costs are high. Preferably, therefore, the entire clean room or a part of the clean room - in particular the shell, and / or the manipulation device, and / or the active substance connection area, and / or the closing device, and / or the filling device, and / or the actuating connection area, and / or the air connection - designed disposable and / or intended for single use.

According to a development of the invention, it is provided that the casing has at least one preferably manually operable intervention device, in particular an intervention glove. Preferably, a part of the shell is designed as an intervention device. This part of the shell is therefore designed for the particular manual intervention, wherein the intervention in the interior of the clean room is feasible. Thus, manual actions in the clean room are possible without opening the clean room.

According to a development of the invention, it is provided that a drive device can be assigned to the supply device, wherein the drive device can be operatively connected to the supply device, preferably via a bushing formed in the casing. The drive device is preferably configured to drive the provision device to a rotation and / or straight, in particular linear. In particular, the drive device can be operatively connected to the provision device such that the at least one medicament container and / or the at least one closure is rotatable, in particular pivotable, and / or in particular linearly displaceable about an axis of rotation of the drive device and / or the provision device, and / or vertically displaceable. Preferably, the supply device is operatively connected to a drive device, in particular operatively connected, such that the receiving device and / or the carrier elements of the delivery device are preferably rotatable, liftable and / or lowerable independently of one another by means of the drive device. For this purpose, the drive device preferably has a shaft, in particular a multiple shaft, very particularly a hollow shaft, and a motor, in particular a servomotor. By means of such a clean room, the filling of medicine containers is further automated and thus quickly and inexpensively feasible. Preferably, the implementation is airtight and sterile sealed formed, so that the arranged outside the clean room drive means can be sealed sealed with the supply device. It is possible in particular that the Drive device is handled separately from the clean room, and it may be particularly preferably integrated into a laboratory bench, which is intended for use with the clean room. But it is also possible that the drive device is arranged in the clean room. The drive device can be designed to be energy self-sufficient and also arranged in the clean room energy storage, in particular an accumulator, so that the actuation of the drive device and thus the provision device no operative connection to the outside is necessary. But it is also possible that the arranged in the clean room drive means is supplied via a sterile and airtight sealed passage with energy. For example, the drive device may be designed as an electric motor, which can then be supplied in particular via a sterile and hermetically sealed electrical feedthrough with electrical power for driving the supply device.

According to one embodiment of the invention it is provided that the shell has on its outer side at least one fastening element and / or in its interior at least one clamping element, in particular a hinged, inner support means for clamping the envelope. By means of such a fastener and / or such Aufspannelements the clean room is held in particular in its second functional state. Thus, the filling of the medicine container is particularly efficient possible. In addition, the displacement of the filling device and / or the displacement of the closure device are possible. In particular, the clean room can be kept in its second, expanded functional state by means of such fastening elements and / or Aufspannelemente even if there is no pressure in the interior of the clean room. In particular, a negative pressure can even be formed in the interior of the clean room if the envelope is held in its expanded form of the second functional state by external fastening elements and / or internal clamping elements. In this way, leakage of hazardous substances, in particular of infectious material, from the clean room into the external environment of the clean room can be prevented in a particularly effective manner.

The object is also achieved by providing a method for producing a transportable clean room, in particular according to one of the preceding embodiments. According to this method, in the environment prevailing with a laminar air flow and / or with cleanliness class A, B or C in accordance with the EU-GMP classification, the version in force on the day determining the priority of the present application is used at least one flexible sheath member is provided, and an agent attachment region is disposed on the sheath member. In addition, at least one actuating connection region, in particular a robot connection region, is arranged on the casing element. In addition, at least one medicament container, a manipulating device having a filling device, and preferably at least one closure for the at least one medicament container are arranged on the flexible casing element and airtightly enclosed with the at least one flexible casing element, so that an airtight, sterile casing is formed. The air-tight enclosing an interior of the shell is formed and separated from an external environment airtight. The active agent connection region is preferably formed in the sheath element or connected to the sheath element. Alternatively or additionally, an air connection, in particular a sterile air connection, is arranged on the casing element, in particular formed in the casing element or connected to the casing element. In addition, a passage is preferably formed in the casing element, by means of which a drive device which can be assigned to the clean room and can be operatively connected to a provision device arranged in the clean room can be carried out. More preferably, the provision device is introduced before the airtight enclosure with the shell in the clean room. In addition, at least one fastening element is preferably provided in or on the sleeve. By means of such a method, a transportable clean room is particularly inexpensive and efficient to produce. Due to the airtight enclosure also the risk of contamination of the clean room is reduced, especially if the clean room is transported in a non-sterile environment, stored or used. A non-sterile environment is to be understood here in particular as meaning a region which has a lower purity, in particular a higher particle density and / or a higher germ number, than the interior of the clean room. In particular, this is understood to mean an area of cleanliness class C or D - in accordance with the EU-GMP classification in the version in force on the day that determines the priority of the present application - and / or an impure environment.

Preferably, the at least one sheath element is cut according to a cutting pattern such that the intended three-dimensional geometry for the clean room results when the at least one sheath element is connected to seam areas provided for this purpose. It is possible that the shell of the clean room is made of a single shell element, which is tightly connected to the airtight enclosing arranged in the clean room components at seams provided for this purpose. It is also possible that the sheath is formed from a plurality of sheath elements, which are then tightly connected together in a corresponding manner. In particular, the at least one casing element is preferably initially spread flat, so that the components to be arranged in the clean room can be arranged on the casing element. Thereafter, the at least one hull element is deformed, in particular collapsed, in such a way that the night stands to be connected are brought into overlap or abutment, after which the at least one hull element is airtight and sterile connected at the intended seams. In this way, the closed shell for the clean room is made. According to one embodiment of the method it is provided that the interior of the shell is subjected to a negative pressure, preferably with a vacuum, such that the shell collapses. Such a method has the advantage that a portable clean room with a particularly small volume is created. This clean room requires very little storage space, and the cost of storage is reduced. In particular, it is possible and economical to produce and store a large number of such transportable clean rooms in stock, so that they can be removed from the storeroom and the medicine containers filled at a later time, when the demand for such transportable clean rooms is high.

According to a further alternative embodiment of the method, it is provided that the clean room is sterilized by means of superheated steam and / or inert gas and / or electromagnetic radiation, in particular gamma radiation, and / or particle radiation, in particular electron radiation. Thus, a particularly safe clean room is created, and the risk of contamination of the clean room is reduced. In particular, it is envisaged to store the clean room in a non-sterile environment, whereby the sterility or the purity of the clean room is not endangered.

The object is also achieved by providing a method for filling a medicament container in a transportable clean room according to one of the preceding embodiments. According to this method, the shell of the clean room is preferably brought into an expanded position by means of an internal support structure and / or an outer support structure and / or a pressurized, preferably gaseous, medium introduced into the interior of the clean room. Also, at least one active ingredient supply is connected to the active ingredient connection area. Furthermore, an actuating device, in particular a robot, connected to the actuating connection region, in particular the robot connection region. In addition, the filling device is preferably coupled to the active agent connection region-if it is not already coupled to it-and the active substance connection region is opened. The filling device and / or the medicament container are preferably arranged relative to one another in a position suitable for filling the medicament container, preferably by means of the manipulation device and / or the provision device. By actuating the filling device, an active substance is introduced into the medicament container. Furthermore, the method comprises opening the clean room by separating the shell, and removing the at least one at least partially filled medicine container. By means of such a method, the filling of a medicament container is particularly safe. In addition, the cost of filling by means of such a method is reduced.

Preferably, the clean room is arranged during the filling in a clean environment, wherein the clean environment preferably has a lower purity class, especially purity class B, C or D, as the interior of the clean room. The clean environment is preferably designed as a stationary clean room, which provides the actuating device, a drive device, an active substance supply and / or an air supply, in particular sterile air supply, for the clean room. As a result, an additional safety mechanism is created, which ensures a leakage of the clean room that contamination of the clean room is at least reduced, in particular avoided. In addition, the costs are reduced compared to a filling in the pure environment without the clean room.

Alternatively, the clean room is arranged during the filling in an impure environment, the cost is particularly low and the process is flexible feasible. Through the clean room and the airtight enclosure with the shell, the safety during filling is ensured even in the impure environment.

The filling device is preferably coupled to the active agent connection region in such a way that the filling device is fluidically connected to the active substance supply, in particular for the automated filling of the medicine container. The separation of the sheath is preferably done by means of a destructive step, more preferably the sheath is cut open. Preferably, after the separation of the shell disposable parts of the clean room disposed of. Particularly preferred is the shell, with the air connection area and / or hoses connected to the active substance connection, parts of the filling device intended for single use, in particular a filling needle, disposing of the air connection region and / or the active ingredient connection region. Preferably, after the filling of the at least one medicine container and before opening, the clean room is brought into a sterile environment in order to be separated there after sterilization and to close the medicament containers manually. Thus, the security of the process is further increased. In addition, the cost of the method is reduced, in particular because parts of the method can be performed in a non-sterile environment, the risk of contamination is not increased. According to one embodiment of the method, it is provided that the at least one medicament container is closed with a closure, in particular a stopper, before the envelope of the clean room is separated. It is preferably provided that the closure means of the closure device of the manipulation device is inserted into the drug container or applied to the drug container. Thus, the risk of contamination of the drug container is reduced. In addition, the clean room can be located throughout the process, especially without increased risk of contamination in the non-sterile environment, so that the cost of the process are low.

According to a further alternative embodiment of the method, it is provided that an air supply, preferably a sterile air supply, is connected to an air connection region, preferably a sterile air connection region, of the clean room, wherein the air connection region is preferably opened. More preferably, the air is filtered by means of an air filter in the air supply and / or in the air connection region and / or in a connecting element, in particular an external and / or internal air hose, between air supply and air connection region. Particularly preferably, a slight overpressure is generated by means of the air supply. Thus, the risk of contamination of the clean room is reduced. Alternatively, it is provided that by means of the air supply, a slight negative pressure in the clean room is generated, so that the safety of the clean room increased by the discharge of hazardous substances is prevented from the clean room.

According to a further embodiment, it is provided that a tightness, a pressure and / or a purity, preferably a particle density and / or a germ count and / or a particle size distribution, of the clean room are monitored. Thus, the safety of the clean room is further increased by a leak of the clean room, especially in the shell of the Clean room, which endangers the purity of the clean room or the safety of the environment of the clean room, can be easily detected.

The descriptions of the clean room, the method of manufacture and the method of filling are to be understood as complementary to each other. In particular, features of the clean room that have been described explicitly or implicitly in connection with the method for producing and / or the method for filling, preferably individually or combined features of the clean room. The clean room is preferably designed to carry out at least one of the method steps described in connection with the method. Process steps which have been described explicitly or implicitly in connection with the clean room are preferably individually or in combination with one another steps of a preferred embodiment of the method for the production and / or the method for filling. In particular, in the context of the method for producing and / or the method for filling, at least one step is preferably provided, which results from at least one feature of the clean room. Overall, it turns out that with the transportable clean room shown here, the method for filling a medicament container in such a portable clean room and the method for producing such a portable clean room means are provided to cost at least one drug container, especially a small number of drug containers fill. In addition, the filling can be carried out particularly quickly by means of such a clean room and / or the method for filling, since the clean room - produced by means of the manufacturing process - in stock, and can be stored compact and inexpensive.

Such a transportable clean room can be used, for example, directly in a clinic, hospital, infirmary or the like to fill sterile quantities of medical active ingredients and / or excipients, especially for individual medical purposes, such facilities as clinics, hospitals, hospitals or the like often do not have their own clean rooms, which meet a prescribed for the filling of drug containers purity classification with the required sterility for this purpose. By contrast, the transportable clean room can have this sterility in its interior, whereby it can be introduced into a less sterile environment and used there to fill the medication container in a sterile manner. Only when the drug containers are sealed in the clean room, they are removed from this, so there is no risk of contamination. The transportable clean room can be used for example in crisis areas, for example, to be able to provide antidotes to pathogens, chemical and / or biological warfare agents or the like quickly and sterile in itself non-sterile environments. In addition, vaccines can be filled quickly and sterile in non-sterile environments. Overall, it is possible with the proposed here portable clean room, under ambient conditions that do not meet a prescribed for the filling of medicinal agents and / or excipients sterility, at least to fill small quantities of drug containers with the required sterility and sterile to close before they then be discharged from the clean room into the non-sterile or at least less sterile environment.

The invention will be explained in more detail below with reference to the drawing. The single figure shows a schematic cross-sectional view of a portable clean room according to an embodiment. The single figure shows in a cross-sectional view a transportable clean room 1, which is enclosed airtight by a shell 3. The shell 3 is at least partially flexible. Preferably, the shell 3 is flexible for the most part and preferably transparent.

In addition, the shell 3 has an apparent active substance connection region 5 and an air connection region 7. In the clean room 1 a plurality of drug containers 9 are arranged, of which here for the sake of clarity, only one is provided with a reference numeral. In addition, a manipulation device 11 is arranged in the clean room 1, which has a filling device 13 and a closing device 15. The filling device 13 is coupled to the active agent connection region 5, in particular by means of a hose 17 fluidly connected thereto. In the embodiment shown here, the filling device 13 also has a filling needle 19, by means of which the active substance can be introduced into the medicament containers 9.

The closing device 15 is designed as a plug setting pin 21. The Stopfensetzstift 21 has an insertable into the drug container 9 sleeve, which is adapted to receive an elastically compressible closure, in particular a plug. The closure device 15 also has a retaining device for in the sleeve recorded plug on. After inserting the sleeve which has received the stopper into the medicament container 9, the stopper in the sleeve is held upwardly by the retainer device. By means of a Relatiwerlagerung between sleeve and retaining device, the plug can be discharged from the sleeve and introduced into the drug container 9, where it adheres due to its elasticity and the medicament container 9 closes. During the Relatiwerlagerung between sleeve and retaining device, the retaining device is preferably held stationary to the drug container 9 and the sleeve led out of the drug container 9, so shifted in Figure 1 upwards. The sheath 3 additionally has an actuating connection region 23, in particular a robot connection region, here in particular a robot flange. By means of an external actuating device 25, in particular an external robot, which is connected from the outside to the actuating connection region 23, in particular flanged, the filling device 13 and the closing device 15 are actuated such that a drug flow controlled by the filling device 13, in particular started and stopped , and the medicament container 9 can be closed by means of the closing device 15. In addition, the manipulation device 11 for the displacement of the filling device 13 and the closing device 15 is set up. In the embodiment shown here, the manipulation device 11 is displaced by means of the actuating device 25, wherein the filling device 13 and the closing device 15 are here fixedly connected to the manipulation device 11, and wherein the manipulation device 11 is fixedly connected to the actuating connection region 23. Thus, the filling device 13, the closing device 15, the manipulation device 11 and the actuating connection region 23 are displaceable jointly by means of the actuating device 25. The sheath 3 is designed to be flexible, in particular in the region around the actuating connection region 23. This is at least one necessary for filling and closing of the drug container 9 displacement of the filling device 13 and the closing device 15 guaranteed.

The clean room 1 also has a provision device 27 which provides the medicament containers 9 and a plurality of closures 29 associated with the medicament containers 9, of which only one is provided with a reference numeral. The closures 29, in particular plugs, are in a closure matrix 31, here in one Plugs matrix arranged, preferably pre-prepared. The medicament containers 9 are arranged in a trough 33, wherein an opening 35 of the respective medicament container 9 faces the respective associated closure 29 and / or the filling device 13 and / or is oriented upwards. The provisioning device 27 also has a plate system 37. The tub 33 with the medicament containers 9 is arranged on a lower plate 39, and the closure matrix 31 with the closures 29 arranged therein is arranged on an upper plate 41. The upper plate 41 and the lower plate 39 are rotatably supported independently of each other about a preferably common axis A.

The supply device 27 is associated with a drive device 43, wherein the drive device 43 of the embodiment shown in Figure 1 is designed as a servo drive. The drive device 43 is operatively connected by means of a hollow shaft 45 to the provision device 27, in particular to the plate system 37 of the delivery device 27. Thus, the two plates 39, 41 of the supply device 27, so the lower plate 39 and the upper plate 41, independently of each other by means of the hollow shaft 45 and a further shaft mounted therein rotatable about the axis A. In addition, the drive means 43 is preferably arranged, the plates 39, 41, the plate system 37 independently raise and lower.

The upper plate 41 preferably has for each closure matrix 31 one or a total of exactly one - in the circumferential direction - spaced from the closure matrix 31 empty matrix, for example, arranged at 90 ° or 180 ° of the circumference of the upper plate 41 spaced from the closure matrix 31 can be. The empty matrix is preferably characterized by a number of openings, in which no plugs are arranged, and through which the filling needle 19 can reach through. The closures 29 and / or the openings of the empty matrix are preferably arranged exactly in a grid which corresponds to the grid in which the medicament containers 9 are arranged in the tub 33. If, therefore, the closures 29 arranged in this grid are positioned over the medicament container 9, the closures 29 can be displaced in a simple manner by the closing device 15 into the medicament containers 9.

On the other hand, if the empty matrix is arranged with the corresponding grid of openings on the medicament containers 9, the filling needle 19 can reach through the openings and fill the medicament containers 9 with the active substance. Of course, it is also possible that, instead of an empty matrix, a large opening, which in particular corresponds approximately to the areal extent of the trough 33, is arranged in the upper plate 41, or the plate 41 is recessed in a suitable manner for filling the medicament containers 9. The shell 3 of the clean room 1 also has a manually operable intervention device 47, here in particular an intervention glove. By means of this intervention device 47, it is possible to intervene manually in a filling process and / or to set up the manipulation device 11 and the provision device 27 preparatory to the filling process. The shell 3 has on its outer side a plurality of fastening elements 49, here in particular six fastening elements 49, for clamping the shell 3. The fasteners 49 in the embodiment shown here are formed as eyelets 51, which cooperate with attached to a table 53 or to an external, not shown here support structure hook 55 to open the shell 3. For the sake of clarity, only one fastening element 49, one eyelet 51 and one hook 55 are provided with a reference numeral in FIG.

Alternatively or additionally, the clean room 1 may also have an inner, arranged in the shell 3 support structure, by means of which it can be brought into the illustrated in the figure, expanded functional state and held in this state, said expanded functional state is also referred to as a second functional state , The clean room 1 can be evacuated via the air connection region 7, so that the casing 3 has a first, collapsed functional state. In this enclosure 3 therefore encloses a smaller volume than in the second functional state. A gas, in particular sterile air, can also be introduced into the casing 3 via the air connection region in order to bring it from the first functional state into the expanded second functional state. The shell 3 can be kept in the second functional state relative to an exterior under pressure or under negative pressure.

The clean room 1 is preferably produced by providing at least one flexible casing element. Then, the at least one active substance connection region 5 is arranged on the casing element, and the at least one actuating connection region 23, in particular the robot connection region, is arranged on the casing element. At least one Drug container, in particular a plurality of medicament containers 9, the manipulation device 11 with the filling device 13 and preferably at least one closure 29 for the at least one medicament container 9 are arranged on the at least one casing element. Subsequently, the at least one medicament container 9, the manipulation device 11, the filling device 13 and preferably the closure 29 are airtightly enclosed with the at least one casing element, so that the casing 3 is formed, which comprises the medicament container 9, the manipulation device 11, the filling device 13 and preferably the encloses at least one closure 29 airtight. The clean room 1 is preferably sterilized by means of superheated steam, an inert gas, electromagnetic radiation, and / or particle radiation, in particular electron radiation.

The medicament container 9 is filled in the clean room 1 by preferably first the casing 3 is brought into its expanded position, wherein at least one active ingredient supply is connected to the active substance connection region 5, and wherein the actuating device 25, in particular the robot, to the actuation connection region 23, in particular the robot connection area, is connected. If the filling device 13 is not already coupled to the active agent connection region 5 in any case, it will now be coupled to it. The active substance connection region is subsequently opened, and at least one active substance is introduced into the medicament container 9 by actuation of the filling device 13. Preferably, the medicament container 9 is subsequently closed with a closure 29. If the medicament containers 9 are filled and closed, the clean room 1 is opened by separating the casing 3, and the at least one filled medicament container 9 is removed.

An air supply, in particular a sterile air supply, is preferably connected to the air connection region 7. Overall, it can be seen that at least one, in particular a plurality of medicament containers 9 can be filled with an active ingredient in a particularly effective and cost-effective manner with the portable clean room 1 shown here. The storage of such clean rooms 1 is inexpensive and space-saving, especially if they are in their first functional state. In addition, the risk of contamination of the clean room 1 is reduced. With the clean room 1 proposed here, medication containers 9 can also be filled in an environment which would otherwise have too low a sterility for filling medication containers 9 having. The clean room 1 can be used in particular for the production of small doses of active substances, for example for individual medicine, but can also be used, for example, in crisis regions for the rapid local provision of active substances, for example antidotes or vaccines.

Claims

1. Transportable clean room (1) for filling at least one in the clean room (1) arranged drug container (9) with at least one active ingredient, wherein the clean room (1) by an at least partially flexible sheath (3) is enclosed airtight, wherein the sheath (3) at least one disclosed active substance connection region (5), and wherein in the clean room (1) a manipulation device (11) and at least one medicament container (9) are arranged, characterized in that the casing (3) at least one actuation connection region (23) wherein the manipulation device (11) has at least one filling device (13) which can be coupled to the active substance connection region (5) for introducing at least one active substance into the at least one medicament container (9) arranged in the clean room (1), and wherein the manipulation device (11) by means of an actuating device (25) via the actuating connection region (23) of the sheath (3) Betätigb ar, and for the displacement of the filling device (13) - is arranged relative to the at least one drug container (9) - and / or for actuating the filling device (13).

2. clean room (1) according to claim 1, characterized in that the manipulation device (11) at least one closing device (15) for closing the at least one drug container (9) with at least one in the clean room (1) arranged closure (29) and for displacing the closing device (15) - relative to the at least one medicament container (9) - and / or for actuating the closing device (15) is set up.

3. clean room (1) according to claim 1 or 2, characterized in that in the clean room (1) a provision device (27) is arranged, which is adapted to the at least one drug container (9) for filling by means of the filling device (13). and / or for sealing with the at least one closure, and / or to provide the at least one closure (29) for closure by means of the closure means (15).

4. clean room (1) according to one of the preceding claims, characterized in that the at least partially flexible sheath (3) in a first functional state of the In a second functional state of the clean room (1) enclosing a second volume airtight, wherein the second volume is greater than the first volume and is so large that the at least one drug container (9) by means the filling device (13) can be filled.

5. clean room (1) according to any one of the preceding claims, characterized in that the sheath (3) at least one air connection area (7), preferably an openable and / or closable sterile air connection area having.

6. clean room (1) according to any one of the preceding claims, characterized in that the sheath (3) is at least partially transparent.

7. clean room (1) according to one of the preceding claims, characterized in that the sheath (3) at least one preferably manually operable intervention device (47), in particular an intervention glove comprises.

8. clean room (1) according to any one of the preceding claims, characterized in that the supply means (27) is a drive means (43) can be assigned, wherein the drive means (43), preferably via a on the sheath (3) formed with the implementation Provision device (27) is operatively connected.

9. clean room (1) according to one of the preceding claims, characterized in that the sheath (3) on its outer side at least one fastening element (49) and / or in its interior at least one clamping element for clamping the sheath (3).

10. A process for producing a transportable clean room (1) with the following steps:

Providing at least one flexible sheath element,

Arranging at least one active substance connection region (5) on the casing element,

Arranging at least one actuating connection region (23) on the casing element,

Arranging at least one medicament container (9), a manipulation device (11) having a filling device (13) and preferably at least one closure (29) for the at least one medicament container (9) on the casing element, and

Air-tightly enclosing the at least one medicament container (9), the manipulation device (11), the filling device (13) and preferably the closure (29) with the casing element, so that a casing (3) is formed which contains the at least one medicament container (9), the manipulation device (11), the filling device (13) and preferably the closure (29) surrounds airtight.

11. The method according to claim 10, characterized in that the interior of the shell (3) is subjected to a negative pressure, preferably with a vacuum, such that the sheath (3) collapses.

12. The method according to claim 10 or 11, characterized in that the clean room (1) by means of superheated steam and / or an inert gas and / or by means of electromagnetic radiation and / or by means of particle radiation, in particular electron radiation, is sterilized.

13. A method for filling a medicament container (9) in a transportable clean room (1) according to one of claims 1 to 9, comprising the following steps:

Bringing the envelope (3) of the clean room (1) into an expanded position, preferably by means of an inner and / or outer support structure and / or by means of a pressurized, preferably gaseous, medium introduced into the interior of the clean room (1),

Connecting at least one active substance supply to the active agent connection region (5),

Connecting an actuating device (25) to the actuating connection region (23), - opening the active agent connection region (5),

Introducing an active substance into the medicament container (9) by actuating the filling device (13), Opening the clean room (1) by separating the sheath (3), and removing the at least one filled medicine container (9).

14. The method according to claim 13, characterized in that the at least one medicament container (9) with a closure (29) is closed before the shell (3) of the clean room (1) is separated.

15. The method according to claim 13 or 14, characterized in that an air supply, preferably a sterile air supply, to an air connection region (7), preferably a sterile air connection region of the clean room (1) is connected.