JP2008500240A - Airtight container for storing products, in particular medicaments, and aseptic method for filling said containers - Google Patents

Abstract

PROBLEM TO BE SOLVED: To propose a new technical solution for storing a product, particularly a drug such as a vaccine, in a container under aseptic conditions.
A rigid vial (2) having at least one filling hole (2c), an external filling tube (5) for filling the vial (2) through the filling hole (2c), the vial (2) An outer filling tube (5) that hermetically seals the filling hole (2c) of the housing and a housing for the filling tube (5) designed to be assembled into the vial (2) and once assembled into the vial (2) ( Airtight container (1), characterized in that it includes a housing cap (12) forming 12a).
[Selection] Figure 2

Description

  The present invention relates generally to hermetic containers used to store products under aseptic conditions. The preferred application of the present invention is preferably a small sized airtight container used in the pharmaceutical field to store drugs such as vaccines.

  In the pharmaceutical field, drugs such as vaccines are usually stored in small sized airtight containers made up of rigid vials, typically made of glass or plastic, and hermetically sealed by a closure cap prior to use. Is done. The closure cap typically does not contaminate the drug and does not affect the drug, and can be manually punctured by using a sharp element such as a syringe or needle to open the vial. Made from vulcanized rubber or similar elastic material.

  For example, when the drug is a liquid, the closure cap is punctured by hand using a syringe and sucked out of the vial. When the drug is a solid, such as a powder, the closure cap is punctured using a syringe or the like, and a liquid, such as water, is introduced into the vial using the syringe. The vial is then shaken to mix the powder and liquid, and the solution in the vial is aspirated from the vial through the closure cap, for example by using a syringe.

  The main technical problem in this technical field is to avoid contamination of the product (medicine etc.) stored in the container and thus ensure sterility inside the container during and also after the filling process.

  According to one known first aseptic filling process, the vial and cap are sterilized separately, then the vial is filled with a drug or the like, and the cap is assembled to the vial to seal the drug in the vial. One major drawback of this first filling process is that it is difficult to maintain the sterility of the cap and vial during the assembly phase. In addition, it is difficult to maintain the sterility of the vial and cap during storage and transport before filling.

  In an attempt to overcome the danger of vial and cap contamination, it has been proposed in the past to use a second aseptic filling process. There: In the first stage, the cap is assembled into a vial to seal the vial hermetically; in the second stage, the vial and cap are sterilized, for example by gamma radiation; in the third stage, the vial is temporarily The drug is filled by using a sterile syringe or similar infusion element inserted through the cap.

  The first major drawback associated with this second aseptic filling process is that a small hole is formed in the cap when the injection member (syringe, needle, etc.) is temporarily inserted through the cap and then withdrawn.

  The hole resulting from the insertion of a needle etc. will shrink somewhat due to the elasticity of the cap. In practice, the small hole formed in the cap is small enough to prevent the drug from leaking out, but is typically sufficient to prevent air or other gases from entering the vial through the hole. Not so small. In addition, elastic materials such as vulcanized rubber are infusible. Therefore, such a material cannot be melted in the field, for example by means of a suitable laser, in order to hermetically close the small hole formed in the cap. Finally, when the second filling step is in use, there is still a high risk of damage and / or contamination of the drug stored in the vial due to this small hole resulting from the insertion of a needle or the like.

  The second major drawback associated with the second filling step described above is that the very small diameter of the needle used to fill the vial makes it difficult to expel air contained in the vial upon filling. The discharge of air typically involves the use of an additional conduit that acts as a vent, and it is difficult to properly meter the drug actually introduced into the vial.

  Further, US Pat. No. 6,604,561 discloses a first base portion formed from a known vulcanized rubber or similar material to provide a stable environment for the drug contained in the vial, and A heat resealable cap is disclosed that includes a second heat resealable portion overlying. In particular, the second heat resealable part is made of low density polyethylene or similar material that can be manually drilled with a needle or the like. The second filling step described above is used to fill the vial with liquid drug, and once the needle or the like has been withdrawn, the holed area of the cap is sealed with a laser or a hole to seal the needlehole of the cap hermetically. Melted by direct heat sealing. The use of the composite cap (heat resealable part / vulcanized rubber base part) disclosed in US Pat. No. 6,604,561 solves the problem of contamination due to the formation of needle holes in the cap after filling.

  However, the use of the composite heat resealable cap disclosed in U.S. Pat. No. 6,604,561 does not solve the above-mentioned main second drawback associated with the discharge of air during filling. In particular, referring to, for example, FIG. 3 of US Pat. No. 6,604,561, an additional vent needle or syringe (reference number “142”) must be used to vent the vial during the filling phase.

  Furthermore, the use of the composite heat resealable cap disclosed in US Pat. No. 6,604,561 includes at least one additional drawback. There is a risk that a part of the liquid contained in the vial will pass through the needle hole made in the vulcanized rubber base part, etc., and harmfully come into contact with the upper heat sealable part of the cap. This heat sealable part is incompatible with this liquid. This risk is higher when the vial is turned over or when the vial and cap are slightly deformed by a small internal negative pressure.

  The object of the present invention is to propose a new technical solution for storing products, in particular (but not limited to) drugs, in a container under aseptic conditions, this solution being sterilized inside the container. And overcomes all the disadvantages of the prior art described above.

  This object is achieved by the new hermetic container of claim 1 and by the aseptic filling method of claim 18.

  The main advantage of the present invention is to avoid any perforation of the container part for filling the container. According to the present invention, the filling of the container is carried out through the filling tube when the filling tube of the container is temporarily opened; therefore, the present invention provides for the formation of holes in the closure cap during the filling stage and the once filling stage. It overcomes all the disadvantages of the prior art associated with closing the hole when finished.

  Furthermore, in one particular embodiment of the invention, the container is closed by a closing element that can be easily and manually punctured by a sharp element such as a syringe or needle for emptying the vial. Sometimes the structure of the closure element can be very simple and the closure element can be made from any material that is compatible with the stored product. In particular, the material need not be resealable.

  Another advantage of the present invention is that, in practice, the filling tube can easily have a diameter that is large enough to allow easy discharge of the air contained in the vial during the filling phase. is there.

  According to a further advantage of the present invention, the instrument used to fill the vial or the instrument used to close the fill tube will be in contact with the fill tube only and must be inside the vial. Does not penetrate.

  Other features and advantages of the present invention will be readily apparent upon consideration of the following detailed description of some preferred embodiments of the invention and the accompanying drawings. These descriptions and drawings are given as non-exhaustive and non-limiting examples of the present invention.

BRIEF DESCRIPTION OF THE DRAWINGS FIG. 1 is a perspective view of an empty container of the present invention prior to the filling stage;
-Figure 2 is a perspective view of half of the container of Figure 1 showing the inside of the container;
FIG. 3 is a cross-sectional view of the bottom of the container before the filling stage, showing a first embodiment for the means for securing the filling tube;
FIG. 4 is a cross-sectional view of the bottom of the container before the filling stage, showing a second embodiment for the fixing means of the filling tube;
FIG. 5 is a cross-sectional view of the end of a filling tube closed by a cap;
FIG. 6 is a cross-sectional view of the end of a filling tube closed by a clip;
FIGS. 7 to 10 schematically show successive steps for filling the container of FIG. 2 with a product (especially liquid or powder or granulate); and FIG. 11 is a perspective view of the final container filled with the product. is there.

  1 and 2 show an empty container 1 according to the invention before aseptic filling with a product (liquid, powder, granules) such as, for example, drugs. However, the present invention is not limited to drug storage and is particularly useful for storing any product under aseptic conditions.

The container 1 is:
A rigid vial 2 constituted by a cylindrical side wall 2a and a bottom wall 2b; said bottom wall 2b has a small central filling hole 2c;
A closure element in the form of a vulcanized rubber cap 3 slidably received in the open end of the vial 2 (opposite the bottom end 2b); such a cap 3 is also commonly referred to as a "stopper";
A fixing ring 4 made, for example, from aluminum or plastic; it is crimped in place on the vial 2 in order to fixably connect the cap 3 to the vial 2 and hermetically seal it;
An additional external filling tube 5 fixed to one end on the bottom wall 2b of the vial 2;
including.

  The vial 2 can be made from any sterilizable and inert material that is compatible with the product to be stored. The vial 2 can be made, for example, from glass or plastic.

  The cap 3 can be made of any sterilizable material that is compatible with the product stored in the container and can be easily and manually punctured by a sharp element such as a needle or syringe. it can. The cap 3 is preferably (but not necessarily) made of an elastic material, more preferably made of vulcanized rubber.

  The filling tube 5 constitutes an internal fluid passage 6 (FIG. 3) having an open base end 6a, and the bottom end of the vial 2 is configured such that the open base end 6a of the fluid passage 6 communicates with the bottom filling hole 2c of the vial 2. 2b is hermetically fixed by any suitable means. In order to avoid any risk of contamination inside the vial 2 it is important that the seal between the filling tube 5 and the vial 2 is airtight.

  In the particular embodiment of FIG. 3, the filling tube 5 has a base end 5a in the form of a “T” and an additional fixing cap 7 that squeezes the base end 5a of the filling tube against the outer surface of the bottom end 2b of the vial 2. To be fixed on the vial 2. Said fixing means does not limit the scope of the invention and can be replaced by any other suitable airtight fixing means. In particular, the base end 5a of the filling tube 5 can be inserted and fixed in an airtight manner through the bottom filling hole 2c of the vial 2 (as shown in FIG. 2). FIG. 4 shows another modification for hermetically fixing the filling tube 5 onto the vial 2. In another variant, the filling tube 5 can be welded onto the vial.

  The fill tube 5 is made from any sterilizable material that is compatible with the product stored inside the vial 2. The tube is preferably flexible, eg made from any biocompatible polymer and in particular any biocompatible elastomer.

  As shown in the particular embodiment of FIG. 3 or FIG. 4, the end 5b of the filling tube is hermetically closed. Therefore, the filling tube 5 hermetically seals the filling hole 2c of the vial 2 in order to avoid accidental intrusion of any contamination (solid, liquid or gas) inside the vial 2.

  In particular, in the embodiment of FIG. 3 or 4, the opening of the end 5b of the filling tube is effected by simply pinching the end 5b of the tube 5 so as to create an internal fluid passage 6 over the entire length of the filling tube (during the filling stage). Can. When the pinch pressure is released, the end 5b of the filling tube 5 returns to its closed state as shown in FIG. 3 or FIG.

The method for aseptic filling with a product such as a medicament in container 1 comprises the following steps.
(A) Sterilize the empty container 1 of FIG. 1 or FIG. 2 by using any known sterilization method, for example by using gamma radiation.
(B) The end 5b of the filling tube of the sterilized empty container 1 is temporarily opened by two jaws 11 (FIG. 7) that pinch the filling tube; Does not penetrate inside. The aseptic filling nozzle 10 is then inserted inside the open end 5b; advantageously, the filling nozzle 10 does not penetrate inside the vial 2, but is inserted only inside the filling tube 5.
(C) A product (eg liquid, powder or granulate) is injected inside the vial 2 through the filling tube 5 and through the bottom filling hole 2c. The outer diameter of the filling nozzle 10 must be smaller than the inner diameter of the filling tube 5 in order to allow the air contained in the vial 2 during this filling stage to be discharged.
(D) The filling nozzle 10 is removed from the filling tube 5 and the end 5b of the filling tube is hermetically closed by releasing the pressure exerted by the jaws 11 (FIG. 8).
(E) Close the filling tube 5 definitely.

  The final closing step (e) can be performed in various ways. For example, the filling tube 5 is pressed to hermetically seal the tube 5 and the end 5b of the tube 5 is thermally sealed (by either a laser or by using any heat source for fusing the ends of the tube. ). The filling tube 5 is then preferably folded as shown in FIG. This can be achieved by mechanical action finally combined with local heating of the tube in order to soften the tube 5 locally. Advantageously, all instruments used to definitely close the filling tube (step (e)) do not contact the inside of the vial 2.

  Finally, the housing cap 12 is fixedly fixed on the bottom end 2 b of the vial 2, which forms a housing 12 a for the tube 5 with the vial 2. The tube 5 is therefore no longer accessible. The housing cap 12 protects the filling tube 5 and avoids any danger of its harmful operation.

  Preferably, the housing cap 12 is first sterilized and then assembled into the vial 2 to avoid any risk of contamination of the filling tube 5.

  In the particular embodiment of FIG. 11, the housing cap 12 also advantageously forms a stable and aesthetic base for the container 1.

  According to the invention, thanks to the use of the outer filling tube 5, it is advantageously not necessary to pierce the vial 2 or the cap 3 during the filling process. Thus, there is no risk of contamination inside the vial by particles, etc. coming from the vial, cap or from any instrument used during the aseptic filling process.

  Also, during the filling stage (c) and the closing stages (d) and (e), the product stored inside the vial 2 is advantageously not exposed to any pressure fluctuations or any thermal fluctuations. Should be noted. Therefore, there is no change in the properties of the product.

  It is important for the present invention that the filling tube 5 is hermetically sealed before the filling stage (b) in order to eliminate any contamination intrusion inside the vial during the process. However, the invention is not limited to the special filling tube shown in FIGS.

  In another variant shown in FIG. 5, the end 5 b of the filling tube 5 is hermetically sealed by a removable cap 8.

  In another variant shown in FIG. 6, the end 5 b of the filling tube 5 is hermetically sealed by a removable clip 9.

  In another variant (not shown), the end 5b of the filling tube 5 can be thermally fused such that it is hermetically closed, and the tube opening (step (b)) is This can be done by cutting the closed end (eg by using a laser or any mechanical cutting means).

  The final container 1 'containing the product is shown in FIG. The container 1 ′ is emptied by piercing the cap 3 (in the region 3 a not surrounded by the fixing ring 4) with a needle or syringe and the product contained inside the vial 2 through the cap 3. This is done by sucking. When the product stored inside the vial is a powder, a liquid such as water is pre-introduced into the inside of the vial 2 through the closure cap 3 in order to dilute the powder and form a solution inside the vial 2 be able to.

  The present invention is not limited to the use of a rubber cap 3 to close the vial 2. In other embodiments of the invention (not shown), the cap 3 can be removed by any closure element that can be removed from the vial during the emptying stage (eg a removable cap screwed into the vial), or the vial Can be replaced by any closure element that can be pierced or torn or torn or torn from the vial.

FIG. 3 is a perspective view of an empty container of the present invention before a filling stage. FIG. 2 is a perspective view of a half of the container of FIG. 1 showing the inside of the container. It is sectional drawing of the bottom part of the container before a filling step. It is sectional drawing of the bottom part of the container before a filling step. FIG. 4 is a cross-sectional view of the end of a filling tube closed by a cap. FIG. 4 is a cross-sectional view of the end of a filling tube closed by a clip. Fig. 3 schematically shows a part of a continuous stage for filling the container of Fig. 2 with a product, in particular a liquid or powder or granulate. Fig. 3 schematically shows a part of a continuous stage for filling the container of Fig. 2 with a product, in particular a liquid or powder or granulate. Fig. 3 schematically shows a part of a continuous stage for filling the container of Fig. 2 with a product, in particular a liquid or powder or granulate. Fig. 3 schematically shows a part of a continuous stage for filling the container of Fig. 2 with a product, in particular a liquid or powder or granulate. FIG. 3 is a perspective view of a final container filled with a product.

Claims (19)

  A rigid vial (2) having at least one filling hole (2c), an external filling tube (5) for filling the vial (2) through the filling hole (2c), the filling hole ( 2c) an outer filling tube (5) that hermetically seals and a housing (12a) for the filling tube (5) designed to be assembled into the vial (2) and once assembled into the vial (2) A hermetic container (1), characterized in that it includes a housing cap (12).   2. Container according to claim 1, characterized in that the filling tube (5) is flexible.   Container according to claim 1 or 2, characterized in that the filling tube (5) can be opened by exerting pressure on the tube.   3. Container according to claim 1 or 2, characterized in that the filling tube (5) is hermetically sealed by a removable cap (8).   3. Container according to claim 1 or 2, characterized in that the filling tube (5) is hermetically sealed by a removable clip (9).   Container according to any one of the preceding claims, characterized in that the vial (2) includes an opening for emptying the vial (2), the opening being closed by a closing element (3). .   7. Container according to claim 6, characterized in that the closure element (3) is made of a material that can be easily punctured by a sharp element such as a syringe or a needle.   8. Container according to claim 7, characterized in that the closure element (3) is made of an elastic material.   9. Container according to claim 8, characterized in that the closure element (3) is made of an elastomeric material.   10. Container according to claim 9, characterized in that the closure element (3) is made from vulcanized rubber.   A filling tube (5) is fixed on the bottom end (2b) of the vial (2), the bottom end (2b) faces the opening for emptying the vial (2), and the bottom end The container according to claim 1 or 6, characterized in that (2b) includes the filling hole (2c).   A container according to any one of the preceding claims, characterized in that the vial (2) is cylindrical.   13. The method according to claim 1, wherein the housing cap (12) forms a stable base for the vial (2) once the housing cap (12) is assembled to the vial (2). Container as described.   14. Container according to any one of the preceding claims, characterized in that the vial (2) contains a product and the filling tube (5) is definitely hermetically sealed.   15. Container according to claim 14, characterized in that the housing cap (12) is definitely assembled to the vial (2) and forms a protective housing (12a) for the filling tube (5).   16. Container according to claim 14 or 15, characterized in that the stored product is selected from the group: liquid, powder, granulate.   17. Container according to any one of claims 14 to 16, characterized in that the product is a drug, in particular a vaccine. 18. Aseptic method for filling a container (1) according to any one of claims 1 to 17 with a product, the method comprising the following steps:
-Sterilize the empty container (1),
-Temporarily opening the filling tube (5) and introducing the product into the inside of the vial (2) through the filling tube (5);
-Sealing the filling tube (5) deterministically and airtightly;
A method comprising the steps of:   19. The housing (12) according to claim 18, characterized in that the housing cap (12) is definitely assembled to the vial (2), said cap (12) forming a protective housing (12a) for the filling tube (5). Method.

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