WO2011048031A1

WO2011048031A1 - Container for pharmaceutical material

Info

Publication number: WO2011048031A1
Application number: PCT/EP2010/065571
Authority: WO
Inventors: Michael Schorpp; Dorothee Ambrosius; Matthaeus Mueller; Franz Nothelfer
Original assignee: Boehringer Ingelheim International Gmbh
Priority date: 2009-10-19
Filing date: 2010-10-15
Publication date: 2011-04-28

Abstract

The invention relates to a carrier for pharmaceutical packaging, comprising two planar parallel plates (1) connected to each other by means of two scissor joints (2), such that the distance between the plates can be changed, wherein each joint comprises means (3) allowing the joint to be fixed.

Description

CONTAINER FOR PHARMACEUTICAL MATERIAL

BACKGROUND OF THE INVENTION

TECHNICAL AREA

The invention relates to an apparatus for shipping, storing and handling frozen pharmaceutical products. More particularly, the invention relates to a container for shipping, storing and handling frozen biopharmaceutical material.

STATE OF THE ART

With advance of the biotechnological industry and the increased demands on the flexibility and cost-efficiency of the quantities of biotechnological products produced, once-usable packaging materials are becoming increasingly important. In addition to the reduced validation costs, these once-usable packaging materials also offer the advantage that they can be used across products, that the costly cleaning procedures are completely eliminated and the investment costs for new production plants can be reduced many times over.

Biopharmaceutical materials in liquid form are increasingly being filled in certain bags, once usable flexible plastic packaging materials The bags consist of several plastic layers, each of which has different properties, including mechanical stability, flexibility, low gas permeability, etc Special characteristics must be the plastic layer that comes into direct contact with the product Films that currently have the most stable properties are eg EVA (Ethylene Vinyl Acetate) or LDPE (Low Density Poly Ethylene) outside (1) to the inside (9) are shown:

1 . ) Nylon

2.) LLDPE

3.) LLDPE

4.) Nylon

5.) EVOH (Ethylene Vinyl -OH) 6.) Nylon

7.) LLDPE

8.) LLDPE

9.) LDPE

Often, however, liquid storage in bags does not provide sufficient long-term stability so that the biopharmaceutical material can be minimized to minimize deleterious effects, e.g. chemical degradation must be frozen. To slow down reaction kinetics as far as possible, a sufficiently low storage temperature must be selected. However, at temperatures below -10 ° C, bags show greatly reduced mechanical stability. A small impact is usually sufficient to cause small cracks that lead to the total loss of content when the biopharmaceutical materials thaw.

In order to avoid mechanical stress on the frozen bags, solutions are already being offered on the market to provide the bag with maximum protection. The patented CELSIUS® system from Sartorius-Stedim (U.S. Patents 6,453,683;

6,684,646; 6,698,213; 6,786,054 and 6,945,056) provides a protective frame in which the bag is frozen and protects it from impact from the side.

However, since the protective frame of the Celsius® system is still open at the front and rear, EnviroCooler® offers freezer containers, which are also designed to ensure safe transport under controlled temperature conditions, and which are described in US Pat. No. 5,924,302. The fundamental disadvantage of this construction is the lack of specificity with regard to the geometry of the goods to be transported, the durability, the inability to clean and above all the further necessary packing of the frozen and thus extremely sensitive bags. A solution for the lack of specificity with respect to the geometry is proposed in a document of the company Human Genome Sciences Inc. (WO2007 / 139873). Here a special container is described, which corresponds to the exact dimensions of the CELSIUS® bags with associated frame. By using plastic materials, this container is easy to clean. However, the problem of packing the frozen bag remains. The system described in US 6,453,683 has the considerable disadvantage that the bag without a special freezer can not be brought into a form in which this space can be stored to save, since the bag is not per se through the frame in one for storage optimized shape is brought. The storage of the frozen bags in the frame without further protective cover still carries the risk of mechanical damage.

The system described in WO2007 / 139873 offers the possibility of storing and shipping bags economically. However, freezing in their containers is not possible within a reasonable time because of the inadequate thermoconvection inside the container. The freezing of the bag with a freezing system inside the container is not possible due to the design of the container.

Both systems also show the common drawback that the bags in the frozen state must be carried by one person at least from the freezer to the protective cover, which is a risk in the sensitivity of the frozen bags.

BRIEF DESCRIPTION OF THE DRAWINGS

Figure 1 shows a carrier according to the invention with two plane-parallel plates (1), which are connected by two scissor hinges (2) with each other so that the distance between the plates is variable. For this purpose, guides for the joint ends are set up on the plates. By means of a locking screw (3), the joint and thus the distance between the plates can be fixed.

Figure 2 shows an embodiment with a molding (4) for suspending a bag.

Figure 3 shows a carrier according to the invention, which is covered with a plastic sheath (6). DESCRIPTION OF THE INVENTION

The present invention overcomes disadvantages of the systems described in the prior art. It is a carrier for pharmaceutical packaging according to Figure 1, consisting of two plane-parallel plates (1) which are connected by two scissor hinges (2) so that the distance between the plates is variable, each joint means (3) contains, which allow a fixing of the joint. Preferably, such a means is a locking screw or locking lever, optionally also a quick-release mechanism or a device for achieving a detected torque. The plates are preferably made of a thermally conductive material, preferably of a metal, more preferably of steel, in particular V2A. The dimensioning of the carrier is suitably adapted to the size of the bags used. A good adaptation to common bag sizes, for example, in a carrier with plate dimensions of 0.5 - 0.6 m x 0.7 -0.8 m (width x length), in a preferred embodiment 0.530 m x 0.710 m. The joints can for example be designed so that a light plate spacing between 0.01 m and 0.30 m is adjustable.

In a preferred embodiment, at least one of the plates has means (4) for attaching a pharmaceutical container. Such a means may be a suitable shape of the plate in the form of a hook or a recess, in which the bag can be hung. Furthermore, it is advantageous if the carrier has a carrying handle (5).

For additional protection, when the carrier contains the packaging material containing the biopharmaceutical material, the carrier may be enveloped in a protective sheath, preferably a plastic film, in particular a gas-impermeable plastic film. A further embodiment therefore relates to the described carrier, characterized in that it is enveloped by a gas-impermeable plastic film (6).

Since the carrier is kept at temperatures below freezing for a longer time in the inventive use, it is important that the materials used are cold-resistant, preferably to -85 ° C. In a further aspect, the invention relates to a method for freezing pharmaceutical preparations which are liquid at temperatures above 0 ° C., in particular aqueous solutions of pharmaceutical active substances, comprising the steps a. a flexible pharmaceutical packaging material is placed between the plates of a carrier as described above, and optionally attached to the carrier, with a predetermined distance of the plates adjusted via the scissors hinges and the hinges fixed in this position;

b. the packaging material is filled with the liquid pharmaceutical preparation in an amount such that more than 50%, preferably more than 80%, of the surface of the packaging material rests on the plates in a conclusive manner;

c. the preparation is frozen in the package between the plates of the carrier using the plates of the carrier for heat exchange.

Preferably, the pharmaceutical preparation thus treated is stored and / or transported in the frozen state in the carrier.

An advantage of the carrier according to the invention is that it allows the setting of a predefined distance of the plates and thus adaptable to different bag sizes and quantities. The bag, preferably a plastic bag, can be placed between the plates and is filled in the carrier with a quantity of fluid sized such that a majority of the bag surface has conclusive contact with the plates, preferably more than 50%, more preferably more than 80%. the bag surface. This allows a good heat transfer through the plates as a heat exchanger in the freezing phase and an optimized storage volume. The packaging-containing liquid is then frozen, expedient by the carrier with the packaging material and the liquid contained therein in a freezing (plate freezer) is introduced.

The bag can also be filled outside the carrier, introduced in the filled state in the carrier and then frozen. Therefore, in a further aspect, the present invention relates to a method for freezing pharmaceutical preparations that are liquid at temperatures above 0 ° C, in particular aqueous solutions of pharmaceutical agents, comprising the steps a. a carrier as described above is set to a maximum plate distance; b. a flexible pharmaceutical packaging filled with a liquid pharmaceutical preparation is introduced into the carrier; c. the plates are moved towards each other so that more than 50%, preferably more than 80% of the surface of the packaging material rest in a conclusive manner on the plates and fixed in this position; d. the preparation is frozen in the package between the plates of the carrier using the plates of the carrier for heat exchange.

Preferably, the carrier is aligned horizontally before the plates are moved toward each other (step (c)). The present invention is particularly suitable for packaging, freezing, storing and transporting aqueous protein solutions.

The invention described here offers the following possibilities:

Complete protective cover in which the bag

o can be clamped in the liquid state

o without having to remove the bag from the protective cover, you must be able to freeze it

o can be frozen in a universal freezer (normal plate freezer)

o can be frozen by using a thermally conductive material in a cold room

o no longer needs to be transported without full protection after freezing, d. H. protected at any time after bottling

o offers the best possible storage volume due to the infinitely adjustable height (defined by the degree of filling of the bag)

The carrier can be used for every bag available on the market. The carrier is reusable

The carrier is easy to clean. Exemplary embodiment: execution of the freezing process

The following example uses a carrier measuring 0.710 m by 0.530 m (length x width of plates) which is universally applicable to many plastic bags currently available on the market. It will also assume a plastic bag measuring 0.654 m by 0.431 m (length x width). The filling volume of the inserted in the protective plastic bag can be varied continuously. The lower filling limit of the plastic bag is defined by the bulge resulting from the degree of filling of the plastic bag and should not fall below a thickness of 0.035 m. The upper filling limit is limited only by the maximum filling volume of the plastic bag used.

The carrier gem. Fig. 1, 2 is completely raised to a plate spacing of 0.275 m and placed vertically on the opposite side of the handle. It follows the on the side mounted screws easy fixation of the degree of opening of the wearer, so that a collapse is no longer possible. In the run-up to specially tailored, cold stable foam parts gem. Fig. 1 (7) inserted in the clamps provided for this purpose. The clamping device are slightly overstretched, so that the inserted foam moldings can be pushed and fixed with slight pressure.

The filled with an aqueous protein solution and labeled on the handle plastic bag which corresponds to the above parameters in terms of type and size, filling volume is suspended in the protective cover in a standing condition in the designated holder from above. After hanging, the protective cover with the plastic bag in it is placed horizontally on a table with the handle side down, so that the plastic bag lying down can assume its full, flat extent. The hoses located on the plastic bag are inserted into the previously clamped foam parts and thus fixed. Loosen the side mounting screws and slowly lower the top of the contactor sleeve onto the plastic bag. The lateral fixing screws are tightened with a defined torque of 10 Nm. The construction of the protective sleeve gives the user the freedom to either put it into a special freezing facility for further processing or simply place it in a freezing cell to freeze the biopharmaceutical content. If a special freezing system is used, it should be constructed like a plate cooler, which moves its cooling plates either in a horizontal or vertical position. An example of a suitable plate cooler are lyophilizers whose cooling plates are in a horizontal position to each other. The variant of the vertical plate cooler can be used by freezing equipment for minced meat or off-shore plate cooler for immediate freezing of fish. Again, cooled, perpendicular to each other plates together to ensure optimum heat transfer to the intermediate Good.

The variant of the horizontal plate cooler will be further described. The

Contact sleeve is placed between two cooling plates, which have the maximum distance to each other. An in-plant guide rail or the like ensures that the protective cover with the plastic container therein is flat without tilting on the cooling plate. Yes, after running the freezer, several plastic bags can be frozen at the same time.

After the plate cooler has been started, the cooling plates, which are held absolutely horizontally by a special design, are moved together with a defined contact pressure, so that all the cooling plates rest on the protective covers with full surface. This ensures optimum heat transfer from the plastic bag via the protective cover to the cooling plates. The contact pressure is defined by the total weight to be moved, which is composed of the degree of loading of the freezing system, the degree of filling of the filled plastic bags and the weight of the cooling plates. The contact pressure must be selected in such a way that all cooling plates rest on the protective sheaths without gaps when the collapse is complete.

After completion of the freezing process, the conditions defined by special temperature programs and dependent on the degree of filling of the system, the cooling plates are moved apart again up to their maximum distance. The protective cover with the inner plastic bag is removed from the handle and inserted into a pre-tempered transport container.

Claims

claims

1 . Carrier for pharmaceutical packaging, consisting of two plane-parallel plates (1) which are interconnected by two scissor hinges (2) such that the distance between the plates is changeable, each hinge containing means (3) allowing the joint to be fixed ,

2. A carrier according to claim 1, characterized in that the means for fixing the joint is a locking screw.

3. A carrier according to claim 1 or 2, characterized in that at least one of the plates has a means (4) for attachment of a pharmaceutical container.

4. Carrier according to one of the preceding claims, characterized in that it comprises a carrying handle (5).

5. Carrier according to one of the preceding claims, characterized in that the plates consist of a thermally conductive material, preferably of a metal, particularly preferably of steel, in particular V2A.

6. Carrier according to one of the preceding claims, characterized in that it is enveloped by a gas-impermeable plastic film (6).

7. A carrier according to any one of the preceding claims, characterized in that the materials used are cold-resistant to -85 ° C.

8. A method for packaging, storing and / or transporting pharmaceutical preparations which are liquid at temperatures above 0 ° C, in particular aqueous solutions of pharmaceutical agents, comprising the steps a. A flexible pharmaceutical packaging is placed between the plates of a carrier according to any one of claims 1 to 7 and optionally attached to the carrier, wherein a predetermined distance of the plates set on the scissor hinges and the joints are fixed in this position; b. the packaging material is filled with the liquid pharmaceutical preparation in an amount such that more than 50%, preferably more than 80%, of the surface of the packaging material rests on the plates in a conclusive manner; c. the preparation is frozen in the packaging between the plates of the carrier, the plates of the carrier being used for heat exchange;

9. The method according to claim 8, characterized in that the thus treated pharmaceutical preparation is stored in the frozen state in the carrier and / or transported.

10. The method according to claim 8 or 9, characterized in that the packaging means is a plastic bag.

1 1. A method for freezing pharmaceutical preparations which are liquid at temperatures above 0 ° C, in particular aqueous solutions of pharmaceutical active substances, comprising the steps of a. a carrier according to one of claims 1 to 7 is set to a maximum plate spacing; b. a flexible pharmaceutical packaging filled with a liquid pharmaceutical preparation is introduced into the carrier; c. the plates are moved towards each other so that more than 50%, preferably more than 80% of the surface of the packaging material rest in a conclusive manner on the plates and fixed in this position; d. the preparation is frozen in the package between the plates of the carrier using the plates of the carrier for heat exchange. A method according to claim 1 1, characterized in that the thus treated pharmaceutical preparation is stored and / or transported in the frozen state in the carrier.

Use of a carrier according to one of claims 1 to 7 for freezing liquid pharmaceutical preparations in flexible pharmaceutical packaging, preferably plastic bags.