CA2128292A1 - Sterile filling system - Google Patents
Sterile filling systemInfo
- Publication number
- CA2128292A1 CA2128292A1 CA 2128292 CA2128292A CA2128292A1 CA 2128292 A1 CA2128292 A1 CA 2128292A1 CA 2128292 CA2128292 CA 2128292 CA 2128292 A CA2128292 A CA 2128292A CA 2128292 A1 CA2128292 A1 CA 2128292A1
- Authority
- CA
- Canada
- Prior art keywords
- filling
- access passageway
- tube
- container
- sterilized
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Abandoned
Links
Abstract
ABSTRACT OF THE INVENTION
The present invention is directed to a method for the on-line sterile filling of a container with a sterile solution from a filling nozzle in a filling head. A container having an open end and a hollow body portion for receiving the sterile solution is provided. The container also includes an access passageway tube having first and second ends and a pierceable septum sealing the passageway at an intermediate position within the tube. The first open end of the access passageway tube is sealed in the open end of the container so as to close the hollow body portion of the container, which is then sterilized. Later, before on line filling, the second end of the access passageway tube is isolated from the surrounding environment by axially advancing and sealably seating the filling head at the second end of the access passageway tube. The isolated end of the access passageway tube is then sterilized for a time period sufficient to reduce the viable micro-organism population present to a predetermined level. Then a filling nozzle is advanced from the filling head through the isolated and sterilized end of the passageway tube and pierces the septum of the tube. After the sterilized hollow body portion is filled with the sterile solution, the access passageway is sealed between the hollow body portion and the filling nozzle.
The present invention is directed to a method for the on-line sterile filling of a container with a sterile solution from a filling nozzle in a filling head. A container having an open end and a hollow body portion for receiving the sterile solution is provided. The container also includes an access passageway tube having first and second ends and a pierceable septum sealing the passageway at an intermediate position within the tube. The first open end of the access passageway tube is sealed in the open end of the container so as to close the hollow body portion of the container, which is then sterilized. Later, before on line filling, the second end of the access passageway tube is isolated from the surrounding environment by axially advancing and sealably seating the filling head at the second end of the access passageway tube. The isolated end of the access passageway tube is then sterilized for a time period sufficient to reduce the viable micro-organism population present to a predetermined level. Then a filling nozzle is advanced from the filling head through the isolated and sterilized end of the passageway tube and pierces the septum of the tube. After the sterilized hollow body portion is filled with the sterile solution, the access passageway is sealed between the hollow body portion and the filling nozzle.
Description
4801 U. S. P1 STEF~ILE FILLING SYSTEM
FIELD OF THE INVENT!ON
This application is a continuation-in-part of commonly assigned pending U. S. patent application Serial No. 07/510,317, filed April 17, 1990 entitled "Method for Sterilizing an Enclosure with Noncondensing Hydrogen Peroxide-Containing Gas." The benefit of the filing date of this prior application is hereby claimed under 35 USC 120.
The present invention relates generally to a method and apparatus for the sterila filling of medical solutions, and more particularly to a method and apparatus that utilizes the on-line sterilization capability of an access passageway to facilitate the subsaquent on-line sterile filling with a sterile medical solution of a pre-sterilized empty container.
BACKGROUND OF THE INVENTION
Parenteral solutions, such as the medical solutions administered in intravenous therapy for example, must be sterile when administered to the patient, and therefore must be starile when packaged and stored.
These sterile solutions were originally packaged in glass bottles and more recently in flexible containers such as plastic film bags. Flexible containers are preferred over glass containers due to advantages such as weight, ease of handling, disposability, and other considerations.
Conventionally the flexible container is fabricated and the solution ^'` 212g292 is sealed in the container. Then the container and solution is terminally sterilized. The flexible container may be further packaged, shipped and then stored until needed.
The flexible container is manufactured of a plastic film or other .~. .
material that is suitably compatible with the medical solution so as to minimize reaction with the solution or allow degradation and/or loss of potency during manufacture and/or storage. Suitable plastic material includes heat sealable PVC film for example.
A terminal sterilization method is selected so that the process is compatible with both the material of the flexible container and the medical solution therein. Suitable terminal sterilization methods include ~ -radiation sterilization and steam autoclaving, for example.
Howover, an increasing number of parenteral administered solutions, such as the new, biotechnically produced drugs, are not necessarily compatible with any combination of the presently known flexible containers and terminal sterilization processes currently in use. For example, some therapeutic solutions packaged in flexible containers lose ;
their potency or change their composition if they are subjected to terminal sterilization by the traditional energy or chemical sterilization procedures. Energy sterilization processes include application of heat such as by steam autociaving, or irradiation with Gamma, X-ray, 21~8292 microwave, plasma, for example. Chemical sterilization may include sterilization by liquid or vapor hydrogen peroxide, ethylene oxide (ETO), phenol, ethanol, or sodium hypochlorite for example.
The United States Food and Drug Administration (FDA) is currently recommending that all medical and surgical products be sterilized to a microbial survival probability of 10-6, an assurance that there is less than one chance in one million that viable micro-organism, such as viruses, bacteria, and spores, are present in the sterilized product.
For a general discussion of sterilization and techniques therefor, see Jhe United States Phar~L~copeia XXII, ch. 1211, pp 1705 et seq., ~ ;;
Atkinson et al., Biochemical Engineering and Biotechnology Handbook, ~ -Stockton Press, New York, N.Y. (1983), pp. 875-886, and Demain et al., M~.rlua~ustrial Microbio!oay and Biotechn~loqy, American Society for Microbiology, Washington, D.C. (1986), pp. 345-362..
Thus there is a need for an alternative sterilization process that can be economically, efficiently, and safely used on-line with current filling processes.
There is also a need for a sterilizing and filling process that avoids using expensive packaging materials, and costly manufacturing and/or sterilization processes for large or small volume sterile packaging of known and new drugs for parenteral administration that have unique and sensitive characteristics, such as for example some of the biotechnically produced solutions or drugs.
SUMMARY OF THE INVENTION
The present invention provides efficient on-line sterilization of an access passageway to a container, including flexible, semi-rigid, or rigid containers and allows for the subsequent sterile filling of the container during an on-line process. The access passageway sterilization process may be accomplished by any one of the variety of known sterilization processes including gas sterilization, vapor sterilization, thermal - ~:
sterilization, radiation sterilization, plasma sterilization, and/or chemical agent sterilization.
The present method has the advantage of achieving a high degree of sterilization efficiency in a relatively short time, since it takes only seconds to sterilize the small volume of the access passageway of a pre-sterilized container. The on-line sterilization of the access passageway can be performed at fluid filling line speeds, thus facilitating use in a sterile filling process.
Thc present invention is directed to a method and apparatus for the on-line sterile filling of a container, including flexible, semi-rigid, or rigid containers, with a sterile solution from an on-line filling mechanism. The container has an open end and a hollow body portion for ~ 2128292 receiving the sterile solution. The container also includes an access passageway tube having firs~ and second ends and a pierceable septum sealing the passageway at an intermediate position within the tube. The first open end of the access passageway tube is sealed to the open end of the container so as to close the hollow body portion of the container. -After the hollow body portion is closed, the container is sterilized, either as a separate operation before the filling operation (i.e. pre-sterilized ;
off-line) or as a step in the filling operation (i.e. on-line). In either situation, when the empty sterilized containers arrive on-line at the filling station, the second end of the access passageway tube is isoiated from the surrounding environment by axially advancing and sealably seating the filling head to the second end of the access passageway tube.
The isolated end of the access passageway tube is then sterilized on-line for a time period sufficient to reduce the viable micro-organism population pr~sent to a predetermined acceptable level. Due to the small volume of the accass passageway, this sterilization can be achieved at on-line filling speeds. Then a filling nozzle is advanced from the filling head through the isolated and sterilized end of the access passageway tube. The nozzle pierces the septum of the tube and the sterilized hollow body portion of the container is filled with the sterils solution. Before the nozzle is withdrawrl from the septum, the filled container is sealed at . . . . . . . . . . . . . ` . . , . . " ~ . . . . . .
;
a point on the container between the hollow body portion and the inserted filling nozzle. The unneeded portion of the access passageway is then detached and the sterile container containing sterile solution is ready for further processing or use.
This invention, both as to its method of operation and apparatus, will be best understood from the following description of spacific embodiments when read in connection with the accompanyiny drawings.
BRIEF DESCRIPTION OF THE DRAWINGS
Figura 1 is a schematic representation of a flexible container having an open end aligned but not attached to a separately fabricated access passageway tube;
Figure 1A is an enlarged perspective view of the separately fabricated access passageway tube of Figure 1;
Figure 2 is a schematic representation of the separately fabricated access passageway tube s0alingly attached and closing the open end of the flexible container;
Figure 2A is a schematic representation of an alternative separately fabricated access passageway tube sealingly attached and closing the open end of a rigid glass container;
Figure 2B is a schematic representation of an integral access passageway fabricated with a semi-rigid container;
: .
212~292 Figure 3 is a schematic representation of a filling head mechanism sealingly positioned at the exposed end of the access passageway tube;
Figure 3A is an enlarged view of the access passageway tube of Figure 3; -~
Figure 3B is an enlarged view of the alternative access passageway tube of Figure 2A sealingly contacted by an alternative filling head;
Figure 4 is a schematic representation of the access passageway tube during sterilization by a representative on-line energy sterilization process;
Figure 4A is an enlarged view of the access passageway tube of Figure 4; ~:
Figure 4B is an enlarged view of the access passageway tube of Figure 4 during sterilization by an alternative on-line chemical sterilization process;
Figure 5 is a schematic representation of a filling nozzle piercing the septum of the access passageway tube; :~
Figure 5A is an enlarged view of th~ access passageway tube of Figure 5; ~ ~ ~
Figure 6 is a schematic representation of a seal produced at the neck ~ ~ :
portion of the filled flexible container prior to the filling nozzle being ~;
withdrawn from the septum;
212~292 8 ~ ~:
Figure 6A is an enlarged view of the access passageway tube of Figure 6;
Figure 7 is a schematic representation of the access passageway tube detached from the sealed neck portion of the fillecl flexible container;
Figure 7A is an enlarged view of the access passageway tube of Figure 7; and Figure 8 is a schematic representation of the access passageway tube after the filling head has been completely withdrawn from one end of the tube and the filled and sealed flexible container is separated from the other end.
DETA!~ED DESCRIPTIONS OF THE PREFERRED EMBODIMENTS
The sterile filling system for practicing the method of this invention is schematically illustrated in Figures 1-8. A container, such as a flexible plastic film bag 12 in Figure 1, or a fabricated paperboard composite container, or a semi-rigid blow molded container, or a rigid glass bottle, is manufactured with an open end 14. For discussion purposes, the container 12 will be described as a flexible container fabricated from two sheets of PVC plastic film, for example. However, other flexible, semi-rigid and rigid container embodiments are also ~;
.................................................................................. ...
considered to be within the scope of this invention The two sheets of . ~
r~
:~ 212~292 g plastic film are sealed together along the edges by any know sealing technique, such as radio frequency (RF), ultrasonic or thermal welding.
The perimeter seal 16 extends along substantially the circumferential perimeter of the flexible container, except for the opening 14, and defines a hollow body portion 18. A hollow body portion is common to all container embodiments of this invention, whether flexible, semi-rigid, rigid or otherwise fabricated.
A separately manufactured access passageway tube 20 is fabricated by molding or extruding a plastic material such as polyethylene or PVC, for example. The access passageway tube 20 is adapted to fit and align with the container opening 14. Alternatively, the access passageway may be fabricated integrally with the container such as by known blow molding or injection molding processes.
Referring now to Figure 1A, the access passageway tube 20 is essentially a hollow tube, preferably cylindrical, although other shapes such as an oval, square, diamond, or triangle are equally useable. In the preferred embodiment, the access passageway tube 20 has two opposed open ends, including a first end 22 and a second end 24. The tube also ~ ~
includes a pierceable septum 26 at an intermediate position within the ~ ~;
hollow passageway which completely divides and closes the passageway.
As shown in Figure 2, the access passageway tube 20 is permanently attached and sealed to the open end 14 of the container. As shown in Figures 2A, a slightly modified access passageway tube 21 is attached and sealed to the outside open end of a glass bottle 23. As shown in Figure 2B
a further modified integral access passageway 25 is fabricated with a semi-rigid blow molded container 27. All of the sealed, empty containers may now be sterilized by any known suitable on-line or off-line sterilizing process prior to being filled with an sterile solution.
Referring now to Figure 3 and 3A, a filling head 30 of the filling mechanism 32 is axially moved into sealing contact with the second end 24 of the access passageway attached to the container.
The second end 24 of the access passageway 20 is sacured in an airtight manner, and the closed volume within the sealed chamber 37 can now be sterilized. A circumferential seal is formed at 36 when the distal, tapered end of the nozzle mandrel 38 with the filling nozzle 34 therein mates with or is removably received at the second end 24 of the access passageway 20. The sealed chamber 37 of the access passageway 20 is isolated from the environment to facilitate fast and efficient sterilization. An alternative embodiment is shown in Figure 3B. ~:
Referring to Figures 4 and 4A, the access passageway is sterilized on-line by passing through an energy sterilization unit such as shown schematically by blocks 40 on both sides of the processing line.
212~292 Alternatively, as seen in Figure 4B, the access passageway can be chemically sterilized with a vapor or liquid introduced into the sealed chamber 37 by lumen 42 associated with the filling nozzle 34. Evacuation and purging can also be accomplished through lumen 40 or additional lumen as needed.
After the access passageway 20 is sterilized, the pierceable septum 26 of passageway is penetrated by the filling nozzle 24, as shown in Figure 5 and 5A. The filling nozzle 34 provides fluid flow communication with a sterile fluid source connected to the filling mechanism 32.
In Figure 4, the sterilization passageway is defined by the mandrel 38 in cooperation with the open end 24 when the distal, tapered end of the mandrel is received therein. The tapered peripheral of mandrel 38 engages ::
:: :
the distal end portion of end 24 to provide a circumferential airtight seal ~. .
39.
Initially filling nozzle 34 is positioned above septum 26 while the access passageway is sterilized. The access passageway 20 can be sterilized, along with that portion of nozzle 34 that is situated within the ;
passageway, with subsequent evacuation and flush purge cycles as required for the contemplated filling operation for the container 12.
Since the container has been pre-sterilized, when the filling nozzle 34 pierces septum 26, the sterile container 12 can be filled with the ::~` 2128292 desired sterile solution.
Thereafter, as can be seen in Figures 6 and 6A, the container is resealed at seal 44 to insure continued sterility of the container and its contents. After the container has been sealed, filling nozzle 34 and mandrel 38 and the unneeded portion of the access passageway 20 are separated from the container 12. Finally as seen in Figure 8, the nozzle head is detached from the unneeded access passageway and positioned for a subsequent sterilization and filling procedure.
Sealing of container 12 at seal 44 can be affected in any convenient manner compatible with the container material and construction.
The present process is well suited for on-line filling operations of off-line sterilized empty containers. This process is useful for the sterilization of biological material which may degrade or loose potency if -~
the material is sterilized in a traditional terminal sterilization manner after the container is filled.
The present process is also cost effective for the later on-line sterile .filling of sterile empty containers previously sterilized by off-line batch sterilization of the empty containers. ~-The above discussion is int0nded by way of example only and is not intended to limit the invention in any way except in the spirit and scope of the appended claims.
FIELD OF THE INVENT!ON
This application is a continuation-in-part of commonly assigned pending U. S. patent application Serial No. 07/510,317, filed April 17, 1990 entitled "Method for Sterilizing an Enclosure with Noncondensing Hydrogen Peroxide-Containing Gas." The benefit of the filing date of this prior application is hereby claimed under 35 USC 120.
The present invention relates generally to a method and apparatus for the sterila filling of medical solutions, and more particularly to a method and apparatus that utilizes the on-line sterilization capability of an access passageway to facilitate the subsaquent on-line sterile filling with a sterile medical solution of a pre-sterilized empty container.
BACKGROUND OF THE INVENTION
Parenteral solutions, such as the medical solutions administered in intravenous therapy for example, must be sterile when administered to the patient, and therefore must be starile when packaged and stored.
These sterile solutions were originally packaged in glass bottles and more recently in flexible containers such as plastic film bags. Flexible containers are preferred over glass containers due to advantages such as weight, ease of handling, disposability, and other considerations.
Conventionally the flexible container is fabricated and the solution ^'` 212g292 is sealed in the container. Then the container and solution is terminally sterilized. The flexible container may be further packaged, shipped and then stored until needed.
The flexible container is manufactured of a plastic film or other .~. .
material that is suitably compatible with the medical solution so as to minimize reaction with the solution or allow degradation and/or loss of potency during manufacture and/or storage. Suitable plastic material includes heat sealable PVC film for example.
A terminal sterilization method is selected so that the process is compatible with both the material of the flexible container and the medical solution therein. Suitable terminal sterilization methods include ~ -radiation sterilization and steam autoclaving, for example.
Howover, an increasing number of parenteral administered solutions, such as the new, biotechnically produced drugs, are not necessarily compatible with any combination of the presently known flexible containers and terminal sterilization processes currently in use. For example, some therapeutic solutions packaged in flexible containers lose ;
their potency or change their composition if they are subjected to terminal sterilization by the traditional energy or chemical sterilization procedures. Energy sterilization processes include application of heat such as by steam autociaving, or irradiation with Gamma, X-ray, 21~8292 microwave, plasma, for example. Chemical sterilization may include sterilization by liquid or vapor hydrogen peroxide, ethylene oxide (ETO), phenol, ethanol, or sodium hypochlorite for example.
The United States Food and Drug Administration (FDA) is currently recommending that all medical and surgical products be sterilized to a microbial survival probability of 10-6, an assurance that there is less than one chance in one million that viable micro-organism, such as viruses, bacteria, and spores, are present in the sterilized product.
For a general discussion of sterilization and techniques therefor, see Jhe United States Phar~L~copeia XXII, ch. 1211, pp 1705 et seq., ~ ;;
Atkinson et al., Biochemical Engineering and Biotechnology Handbook, ~ -Stockton Press, New York, N.Y. (1983), pp. 875-886, and Demain et al., M~.rlua~ustrial Microbio!oay and Biotechn~loqy, American Society for Microbiology, Washington, D.C. (1986), pp. 345-362..
Thus there is a need for an alternative sterilization process that can be economically, efficiently, and safely used on-line with current filling processes.
There is also a need for a sterilizing and filling process that avoids using expensive packaging materials, and costly manufacturing and/or sterilization processes for large or small volume sterile packaging of known and new drugs for parenteral administration that have unique and sensitive characteristics, such as for example some of the biotechnically produced solutions or drugs.
SUMMARY OF THE INVENTION
The present invention provides efficient on-line sterilization of an access passageway to a container, including flexible, semi-rigid, or rigid containers and allows for the subsequent sterile filling of the container during an on-line process. The access passageway sterilization process may be accomplished by any one of the variety of known sterilization processes including gas sterilization, vapor sterilization, thermal - ~:
sterilization, radiation sterilization, plasma sterilization, and/or chemical agent sterilization.
The present method has the advantage of achieving a high degree of sterilization efficiency in a relatively short time, since it takes only seconds to sterilize the small volume of the access passageway of a pre-sterilized container. The on-line sterilization of the access passageway can be performed at fluid filling line speeds, thus facilitating use in a sterile filling process.
Thc present invention is directed to a method and apparatus for the on-line sterile filling of a container, including flexible, semi-rigid, or rigid containers, with a sterile solution from an on-line filling mechanism. The container has an open end and a hollow body portion for ~ 2128292 receiving the sterile solution. The container also includes an access passageway tube having firs~ and second ends and a pierceable septum sealing the passageway at an intermediate position within the tube. The first open end of the access passageway tube is sealed to the open end of the container so as to close the hollow body portion of the container. -After the hollow body portion is closed, the container is sterilized, either as a separate operation before the filling operation (i.e. pre-sterilized ;
off-line) or as a step in the filling operation (i.e. on-line). In either situation, when the empty sterilized containers arrive on-line at the filling station, the second end of the access passageway tube is isoiated from the surrounding environment by axially advancing and sealably seating the filling head to the second end of the access passageway tube.
The isolated end of the access passageway tube is then sterilized on-line for a time period sufficient to reduce the viable micro-organism population pr~sent to a predetermined acceptable level. Due to the small volume of the accass passageway, this sterilization can be achieved at on-line filling speeds. Then a filling nozzle is advanced from the filling head through the isolated and sterilized end of the access passageway tube. The nozzle pierces the septum of the tube and the sterilized hollow body portion of the container is filled with the sterils solution. Before the nozzle is withdrawrl from the septum, the filled container is sealed at . . . . . . . . . . . . . ` . . , . . " ~ . . . . . .
;
a point on the container between the hollow body portion and the inserted filling nozzle. The unneeded portion of the access passageway is then detached and the sterile container containing sterile solution is ready for further processing or use.
This invention, both as to its method of operation and apparatus, will be best understood from the following description of spacific embodiments when read in connection with the accompanyiny drawings.
BRIEF DESCRIPTION OF THE DRAWINGS
Figura 1 is a schematic representation of a flexible container having an open end aligned but not attached to a separately fabricated access passageway tube;
Figure 1A is an enlarged perspective view of the separately fabricated access passageway tube of Figure 1;
Figure 2 is a schematic representation of the separately fabricated access passageway tube s0alingly attached and closing the open end of the flexible container;
Figure 2A is a schematic representation of an alternative separately fabricated access passageway tube sealingly attached and closing the open end of a rigid glass container;
Figure 2B is a schematic representation of an integral access passageway fabricated with a semi-rigid container;
: .
212~292 Figure 3 is a schematic representation of a filling head mechanism sealingly positioned at the exposed end of the access passageway tube;
Figure 3A is an enlarged view of the access passageway tube of Figure 3; -~
Figure 3B is an enlarged view of the alternative access passageway tube of Figure 2A sealingly contacted by an alternative filling head;
Figure 4 is a schematic representation of the access passageway tube during sterilization by a representative on-line energy sterilization process;
Figure 4A is an enlarged view of the access passageway tube of Figure 4; ~:
Figure 4B is an enlarged view of the access passageway tube of Figure 4 during sterilization by an alternative on-line chemical sterilization process;
Figure 5 is a schematic representation of a filling nozzle piercing the septum of the access passageway tube; :~
Figure 5A is an enlarged view of th~ access passageway tube of Figure 5; ~ ~ ~
Figure 6 is a schematic representation of a seal produced at the neck ~ ~ :
portion of the filled flexible container prior to the filling nozzle being ~;
withdrawn from the septum;
212~292 8 ~ ~:
Figure 6A is an enlarged view of the access passageway tube of Figure 6;
Figure 7 is a schematic representation of the access passageway tube detached from the sealed neck portion of the fillecl flexible container;
Figure 7A is an enlarged view of the access passageway tube of Figure 7; and Figure 8 is a schematic representation of the access passageway tube after the filling head has been completely withdrawn from one end of the tube and the filled and sealed flexible container is separated from the other end.
DETA!~ED DESCRIPTIONS OF THE PREFERRED EMBODIMENTS
The sterile filling system for practicing the method of this invention is schematically illustrated in Figures 1-8. A container, such as a flexible plastic film bag 12 in Figure 1, or a fabricated paperboard composite container, or a semi-rigid blow molded container, or a rigid glass bottle, is manufactured with an open end 14. For discussion purposes, the container 12 will be described as a flexible container fabricated from two sheets of PVC plastic film, for example. However, other flexible, semi-rigid and rigid container embodiments are also ~;
.................................................................................. ...
considered to be within the scope of this invention The two sheets of . ~
r~
:~ 212~292 g plastic film are sealed together along the edges by any know sealing technique, such as radio frequency (RF), ultrasonic or thermal welding.
The perimeter seal 16 extends along substantially the circumferential perimeter of the flexible container, except for the opening 14, and defines a hollow body portion 18. A hollow body portion is common to all container embodiments of this invention, whether flexible, semi-rigid, rigid or otherwise fabricated.
A separately manufactured access passageway tube 20 is fabricated by molding or extruding a plastic material such as polyethylene or PVC, for example. The access passageway tube 20 is adapted to fit and align with the container opening 14. Alternatively, the access passageway may be fabricated integrally with the container such as by known blow molding or injection molding processes.
Referring now to Figure 1A, the access passageway tube 20 is essentially a hollow tube, preferably cylindrical, although other shapes such as an oval, square, diamond, or triangle are equally useable. In the preferred embodiment, the access passageway tube 20 has two opposed open ends, including a first end 22 and a second end 24. The tube also ~ ~
includes a pierceable septum 26 at an intermediate position within the ~ ~;
hollow passageway which completely divides and closes the passageway.
As shown in Figure 2, the access passageway tube 20 is permanently attached and sealed to the open end 14 of the container. As shown in Figures 2A, a slightly modified access passageway tube 21 is attached and sealed to the outside open end of a glass bottle 23. As shown in Figure 2B
a further modified integral access passageway 25 is fabricated with a semi-rigid blow molded container 27. All of the sealed, empty containers may now be sterilized by any known suitable on-line or off-line sterilizing process prior to being filled with an sterile solution.
Referring now to Figure 3 and 3A, a filling head 30 of the filling mechanism 32 is axially moved into sealing contact with the second end 24 of the access passageway attached to the container.
The second end 24 of the access passageway 20 is sacured in an airtight manner, and the closed volume within the sealed chamber 37 can now be sterilized. A circumferential seal is formed at 36 when the distal, tapered end of the nozzle mandrel 38 with the filling nozzle 34 therein mates with or is removably received at the second end 24 of the access passageway 20. The sealed chamber 37 of the access passageway 20 is isolated from the environment to facilitate fast and efficient sterilization. An alternative embodiment is shown in Figure 3B. ~:
Referring to Figures 4 and 4A, the access passageway is sterilized on-line by passing through an energy sterilization unit such as shown schematically by blocks 40 on both sides of the processing line.
212~292 Alternatively, as seen in Figure 4B, the access passageway can be chemically sterilized with a vapor or liquid introduced into the sealed chamber 37 by lumen 42 associated with the filling nozzle 34. Evacuation and purging can also be accomplished through lumen 40 or additional lumen as needed.
After the access passageway 20 is sterilized, the pierceable septum 26 of passageway is penetrated by the filling nozzle 24, as shown in Figure 5 and 5A. The filling nozzle 34 provides fluid flow communication with a sterile fluid source connected to the filling mechanism 32.
In Figure 4, the sterilization passageway is defined by the mandrel 38 in cooperation with the open end 24 when the distal, tapered end of the mandrel is received therein. The tapered peripheral of mandrel 38 engages ::
:: :
the distal end portion of end 24 to provide a circumferential airtight seal ~. .
39.
Initially filling nozzle 34 is positioned above septum 26 while the access passageway is sterilized. The access passageway 20 can be sterilized, along with that portion of nozzle 34 that is situated within the ;
passageway, with subsequent evacuation and flush purge cycles as required for the contemplated filling operation for the container 12.
Since the container has been pre-sterilized, when the filling nozzle 34 pierces septum 26, the sterile container 12 can be filled with the ::~` 2128292 desired sterile solution.
Thereafter, as can be seen in Figures 6 and 6A, the container is resealed at seal 44 to insure continued sterility of the container and its contents. After the container has been sealed, filling nozzle 34 and mandrel 38 and the unneeded portion of the access passageway 20 are separated from the container 12. Finally as seen in Figure 8, the nozzle head is detached from the unneeded access passageway and positioned for a subsequent sterilization and filling procedure.
Sealing of container 12 at seal 44 can be affected in any convenient manner compatible with the container material and construction.
The present process is well suited for on-line filling operations of off-line sterilized empty containers. This process is useful for the sterilization of biological material which may degrade or loose potency if -~
the material is sterilized in a traditional terminal sterilization manner after the container is filled.
The present process is also cost effective for the later on-line sterile .filling of sterile empty containers previously sterilized by off-line batch sterilization of the empty containers. ~-The above discussion is int0nded by way of example only and is not intended to limit the invention in any way except in the spirit and scope of the appended claims.
Claims (13)
1. A method for the on-line sterile filling of a container with a sterile solution from a filling nozzle in a filling head, which comprises the steps of:
providing a container having an open end and a hollow body portion for receiving the sterile solution;
providing an access passageway tube, the access passageway tube having first and second open ends and a pierceable septum sealing the passageway at an intermediate position within the tube;
sealing the first open end of the access passageway tube in the open end of the container so as to close the hollow body portion of the container;
sterilizing the closed hollow body portion of the container;
isolating the second open end of the access passageway tube from the surrounding environment by axially advancing and sealably seating the filling head within the second open end of the access passageway tube;
sterilizing the isolated end of the access passageway tube for a time period sufficient to reduce the viable micro-organism population present to a predetermined level;
axially advancing a filling nozzle from the filling head through the isolated and sterilized end of the access passageway tube and piercing the septum of the tube;
filling the sterilized hollow body portion of the container with the sterile solution; and sealing the access passageway between the hollow body portion and the filling nozzle.
providing a container having an open end and a hollow body portion for receiving the sterile solution;
providing an access passageway tube, the access passageway tube having first and second open ends and a pierceable septum sealing the passageway at an intermediate position within the tube;
sealing the first open end of the access passageway tube in the open end of the container so as to close the hollow body portion of the container;
sterilizing the closed hollow body portion of the container;
isolating the second open end of the access passageway tube from the surrounding environment by axially advancing and sealably seating the filling head within the second open end of the access passageway tube;
sterilizing the isolated end of the access passageway tube for a time period sufficient to reduce the viable micro-organism population present to a predetermined level;
axially advancing a filling nozzle from the filling head through the isolated and sterilized end of the access passageway tube and piercing the septum of the tube;
filling the sterilized hollow body portion of the container with the sterile solution; and sealing the access passageway between the hollow body portion and the filling nozzle.
2. The method for on-line sterile filling in claim 1 wherein the access passageway tube is sterilized by a gas sterilization process.
3. The method for on-line sterile filling in claim 1 wherein the access passageway tube is sterilized by a vapor sterilization process.
4. The method for on-line sterile filling in claim 1 wherein the access passageway tube is sterilized by a thermal sterilization process.
5. The method for on-line sterile filling in claim 1 wherein the access passageway tube is sterilized by a plasma sterilization process.
6. The method for on-line sterile filling in claim 1 wherein the access passageway tube is sterilized by a chemical sterilization process.
7. A sterile fill method for filling a sterile container with a flowable material which comprises the steps of:
providing a closed sterile container that defines a hollow body portion for receiving the flowable material and is equipped with an access passageway that communicates with the hollow body portion and a pierceable septum sealing the access passageway at an intermediate position;
providing an axially moveable filling head having an advanceable filling nozzle;
isolating the access passageway from the surrounding environment by sealably seating within the access passageway a filling head;
sterilizing the isolated passageway for a time period sufficient to reduce the viable micro-organism population present to a predetermined level;
advancing the filling nozzle so as to pierce the septum, and penetrating therethrough to provide communication with the hollow body portion;
dispensing the flowable material into the hollow body portion;
sealing the access passageway between the hollow body portion and the filling nozzle while the filling nozzle penetrates the pierced septum;
and withdrawing the filling nozzle from the access passageway.
providing a closed sterile container that defines a hollow body portion for receiving the flowable material and is equipped with an access passageway that communicates with the hollow body portion and a pierceable septum sealing the access passageway at an intermediate position;
providing an axially moveable filling head having an advanceable filling nozzle;
isolating the access passageway from the surrounding environment by sealably seating within the access passageway a filling head;
sterilizing the isolated passageway for a time period sufficient to reduce the viable micro-organism population present to a predetermined level;
advancing the filling nozzle so as to pierce the septum, and penetrating therethrough to provide communication with the hollow body portion;
dispensing the flowable material into the hollow body portion;
sealing the access passageway between the hollow body portion and the filling nozzle while the filling nozzle penetrates the pierced septum;
and withdrawing the filling nozzle from the access passageway.
8. The method for sterilizing in claim 7 wherein the chamber is sterilized by a gas sterilization process.
9. The method for sterilizing in claim 7 wherein the chamber is sterilized by a vapor sterilization process.
10. The method for sterilizing in claim 7 wherein the chamber is sterilized by a heat sterilization process.
11. The method for sterilizing in claim 7 wherein the chamber is sterilized by a plasma reduction process.
12. The method for sterilizing in claim 7 wherein the chamber is sterilized by a chemical process.
13. A method for the on-line sterile filling of a container with a sterile solution from a filling nozzle in a filling head, which comprises the steps of:
providing a container having an open end and a hollow body portion for receiving the sterile solution;
providing an access passageway tube, the access passageway tube having at least a first open end and a second end and a pierceable septum sealing the passageway at a position within the tube;
sealing the first open end of the access passageway tube to the open end of the container so as to close the hollow body portion of the container;
sterilizing the closed hollow body portion of the container;
isolating the second end of the access passageway tube from the surrounding environment by axially advancing and sealably seating the filling head around the second end of the access passageway tube;
sterilizing the isolated end of the access passageway tube for a time period sufficient to reduce the viable micro-organism population present to a predetermined level;
axially advancing a filling nozzle from the filling head through the isolated and sterilized end of the passageway tube and piercing the septum of the tube;
filling the sterilized hollow body portion of the container with the sterile solution; and sealing the access passageway between the hollow body portion and the filling nozzle.
providing a container having an open end and a hollow body portion for receiving the sterile solution;
providing an access passageway tube, the access passageway tube having at least a first open end and a second end and a pierceable septum sealing the passageway at a position within the tube;
sealing the first open end of the access passageway tube to the open end of the container so as to close the hollow body portion of the container;
sterilizing the closed hollow body portion of the container;
isolating the second end of the access passageway tube from the surrounding environment by axially advancing and sealably seating the filling head around the second end of the access passageway tube;
sterilizing the isolated end of the access passageway tube for a time period sufficient to reduce the viable micro-organism population present to a predetermined level;
axially advancing a filling nozzle from the filling head through the isolated and sterilized end of the passageway tube and piercing the septum of the tube;
filling the sterilized hollow body portion of the container with the sterile solution; and sealing the access passageway between the hollow body portion and the filling nozzle.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US093,297 | 1987-09-04 | ||
| US08/093,297 US5382406A (en) | 1990-04-17 | 1993-07-16 | Sterile filling method |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2128292A1 true CA2128292A1 (en) | 1995-01-17 |
Family
ID=22238186
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA 2128292 Abandoned CA2128292A1 (en) | 1993-07-16 | 1994-07-18 | Sterile filling system |
Country Status (1)
| Country | Link |
|---|---|
| CA (1) | CA2128292A1 (en) |
-
1994
- 1994-07-18 CA CA 2128292 patent/CA2128292A1/en not_active Abandoned
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| Date | Code | Title | Description |
|---|---|---|---|
| FZDE | Dead |