WO2002043790A1

WO2002043790A1 - Pocket system and method for viral inactivation of a fluid from which leukocytes have been previously eliminated

Info

Publication number: WO2002043790A1
Application number: PCT/FR2001/003751
Authority: WO
Inventors: Francis Goudaliez; Thierry Verpoort
Original assignee: Maco Pharma
Priority date: 2000-11-29
Filing date: 2001-11-27
Publication date: 2002-06-06
Also published as: FR2817152B1; AU2002222063A1; FR2817152A1

Abstract

The invention concerns a pocket system (1) for viral inactivation, in closed circuit, of a biological fluid using a virucide substance (2), of the type comprising an inactivation pocket (3) in fluid communication with a container (4) containing the virucide substance (2) and an inlet (5) of a collecting pocket (6) via a filter (7) adapted to eliminate the virucide substance (2), said system (1) comprising a first pipe (16) provided at its upstream end (16a) with means (17) designed for introducing into the system (1) the biological fluid to be inactivated, said pipe (16) being connected, through its downstream end (16b), directly to an inlet (12) of the container (4).

Description

POCKET SYSTEM AND METHOD FOR VIRAL INACTIVATION OF A PRE-DELEUCOCYTE FLUID

The invention relates to a bag system for viral inactivation, in a closed circuit, of a biological fluid using a virucidal substance, as well as to its implementation method.

It typically applies to viral inactivation of blood or a blood component, in particular that of a blood plasma.

There are already known, in particular from document EP-A-0 933 090, bag systems which comprise an inactivation bag in fluid communication on the one hand with a container containing the virucidal substance and on the other hand with an orifice entry of a collection bag via a filter capable of removing the virucidal substance.

Such systems make it possible to carry out in closed circuit:

- the addition of the virucidal substance in the fluid; - the viral inactivation treatment of the fluid present in the inactivation bag;

- removal by filtration of the virucidal substance added to the fluid; and

- the collection of the inactivated fluid and devoid of virucidal substance in the collection bag.

However, the system described in document EP-0 933 090 further comprises a leukocyte filter placed upstream of the container so as to carry out, prior to inactivation, the leukocyte removal from the blood.

This type of system has the particular disadvantage of providing for leukoreduction and inactivation in a dependent manner. However, it may be desirable to dissociate these two treatments by planning to carry them out in separate systems, in particular in the case where all the fluid must be leukoreduced but where it must not necessarily be inactivated using a virucidal substance .

For example, leukoreduced blood plasma can be used either for therapeutic purposes and be inactivated using a virucidal substance before its transfusion or for fractionation purposes and be inactivated during said fractionation.

The invention therefore aims in particular to remedy this drawback by providing a bag system for viral inactivation which is devoid of a leukocyte filter.

Thus, leukoreduction of the fluid can be carried out using a separate system without taking into account the inactivation process that the fluid may eventually have to undergo, then, depending on the needs, all or part of the fluid can be inactivated by closed circuit using a virucidal substance.

To this end, and according to a first aspect, the invention provides a bag system for viral inactivation, in a closed circuit, of a biological fluid using a virucidal substance, of the type comprising a bag of inactivation in fluid communication on the one hand with a container containing the virucidal substance and on the other hand with an inlet orifice of a collection bag via a filter capable of eliminating the virucidal substance, said system comprising a first tube provided with its upstream end of means arranged to allow the introduction into the system of the biological fluid to be inactivated, said tubing being connected, by its downstream end, directly to an inlet orifice of the container.

According to a second aspect, the invention proposes a method of implementing such a bag system, said method providing for the successive stages of: - Introducing into the bag system the fluid to be inactivated by means arranged to allow this introduction;

- Pass the fluid into the inactivation bag via the container so that the inactivation bag contains the fluid containing the virucidal substance;

- apply to the fluid contained in the inactivation bag radiation capable of inactivating any viruses it contains;

- pass the fluid into the collection bag via the filter so that the fluid transferred into the collection bag is inactivated and devoid of virucidal substance.

Other objects and advantages of the invention will appear during the description which follows with reference to the accompanying drawings.

Figure 1 shows, in front view and schematically, an embodiment of a bag system according to the invention.

Figure 2 shows, in front view and schematically, an inactivation bag in which the filter is arranged in an outlet compartment.

Figures 3 and 4 show, in front view and schematically, an inactivation pocket and a container disposed in the vicinity of one of its inlet orifices respectively inside and outside the pocket inactivation.

FIG. 1 shows an embodiment of a bag system 1 for viral inactivation, in a closed circuit, of a biological fluid using a virucidal substance 2.

In a particular example, such a system 1 is intended for viral inactivation of blood or of a blood component previously leukoreduced, in particular to that of a blood plasma for therapeutic use, that is to say having to be transfused to a patient as opposed to a fractionating plasma which is intended to be fractionated into its various constituents so as for example to be used in the manufacture of medicaments.

To this end, the virucidal substance 2 which comprises, for example, methylene blue or its derivatives, is added to the biological fluid with a view to subjecting it to a photodynamic inactivation treatment.

Additives such as mannitol and / or polyol and / or leucine can be added to the virucidal substance 2 so as to ensure its stability during sterilization but also to obtain good quality of manufacture, dosage and solubility.

This treatment, which will not be described in detail here, is based on photochemical reactions between the virucidal substance and the DNA or viral RNA possibly present in the biological fluid.

Indeed, exposure to light of the virucidal substance causes a photochemical reaction which transmits energy to the DNA and RNA molecules so that the virus is inactivated.

The bag system 1 represented in FIG. 1 comprises an inactivation bag 3 in fluid communication on the one hand with a container 4 containing the virucidal substance 2 and on the other hand with an inlet orifice 5 of a bag of collection 6 via a filter 7 capable of eliminating the virucidal substance 2.

The inactivation and collection pockets 3 which may be identical or different, for example comprise an outer envelope formed by two sheets of plastic material assembled by welding on their periphery so as to define an interior volume 8.

The sheets are formed from biocompatible, flexible, sterilizable plastic material and, at least for those of the inactivation bag 3, transparent to light radiation, for example polyvinyl chloride. In addition, inlet 5 and / or outlet 9 orifices are provided between the sheets so as to be able respectively to supply the interior volume 8 with fluid and to transfer said fluid outside said interior volume 8.

In the embodiment shown in FIGS. 1, 3 and 4, two other orifices 10 are conventionally arranged on the same side of the envelope as the inlet 5 and / or outlet orifices 9. The two orifices 10 are closed tightly and sterile by a device 11 which can be torn if the operator wishes to use them as a second inlet and / or outlet.

The container 4 containing the virucidal substance 2 is formed by a portion of tubing provided with an inlet orifice 12 and an outlet orifice 13 between which the virucidal substance 2 is placed.

To this end, the virucidal substance 2 can be in the form of a pellet and the tubing portion can be formed by two half-shells made of rigid plastic material in which is provided a drilled housing capable of receiving said pellet. In this embodiment, the pellet, after assembly of the two half-shells, remains inside the container 4 during the manipulation of the system 1 and is dissolved by the passage of the fluid in the container 4.

The filter 7 capable of removing the virucidal substance 2 comprises a filtering medium 14 which is, for example, placed in a flexible bag 15 such as that described in document EP-A-0 526 678, the description of which will not be repeated here.

According to one embodiment, the filtering medium 14 is produced from at least one hydrophilic material in the form of a porous nonwoven and / or of a porous membrane capable of absorbing and / or adsorbing the virucidal substance 2.

In the case of the treatment of a blood plasma containing methylene blue, let us cite among the possible materials, polymers and / or copolymers based on polyester, acrylonitrile, polyvinylidene fluoride. Such filters 7 capable of removing the virucidal substance are for example described in the document FR-99 13 089, the description of which will not be repeated here.

The system 1 shown in FIG. 1, comprises a first tube 16 provided at its upstream end 16a with means 17 arranged to allow the introduction into the system 1 of the biological fluid to be inactivated, said tube

16 being connected, by its downstream end 16b, directly to the inlet orifice 12 of the container 4.

In the description, the terms “upstream” and “downstream” are defined respectively with respect to the direction of circulation of the fluid from the means

17 to the collection bag 6.

The term "directly" means that no device, and in particular no leukocyte filter, is disposed on the path of flow of the fluid in the first tube 16.

The means 17 are for example means for placing in communication or means for connecting with means for placing in communication of the system 1 with the contents of a pocket (not shown) containing the fluid to be inactivated, for example formed of a puncher.

The system 1 shown in FIG. 1 further comprises:

- A second tube 18 whose downstream end 18b is connected to an inlet orifice 5 of the inactivation bag 3 and whose upstream end 18a is connected to the outlet orifice 13 of the container 4 containing the virucidal substance 2;

- A third tube 19 whose upstream end 19a is connected to an outlet orifice 9 of the inactivation bag 3 and whose downstream end 19b is connected to an inlet orifice 20 of the filter 7; a fourth tube 21 whose upstream end 21a is connected to an outlet orifice 22 of the filter 7 and whose downstream end 21b is connected to an inlet orifice 5 of the collection bag 6.

In another embodiment shown in FIG. 2, the filter 7 is arranged in an outlet compartment 23, formed for example by a weld line 24, of the inactivation pocket 3.

The internal volume 8 of the inactivation bag 3 containing the fluid then communicates, via an orifice 25 formed in the weld line 24, with the filter 7, either directly in the case where the filter medium 14 is disposed directly in compartment 23 and the system 1 then no longer comprises a third tube 19, either by means of a tube 26 in the case where the filter 7 is arranged in compartment 23 (FIG. 2).

In this embodiment, the inlet 5 and outlet 9 orifices of the inactivation bag 3 are distributed on either side of the envelope.

In a further embodiment, the container 4 is arranged in the vicinity or in an inlet orifice 5 of the inactivation bag 3 so that the system 1 no longer comprises a second tube 18.

For example, the container 4 can be placed inside the internal volume 8 (FIG. 3) or outside (FIG. 4) thereof, on the downstream end 16b of the first tube 16.

The steps of the method for implementing the bag system 1 represented in FIG. 1 for the viral inactivation, in a closed circuit, of a blood plasma are described below.

The plasma, which has been leukoreduced beforehand, for example by closed circuit filtration, is collected in a pocket. Depending on the plasma requirements for therapeutic use, the bag can then be connected to the bag system 1 by means 17 provided for this purpose so as to supply the system 1 with plasma to be inactivated using the substance. virucidal 2.

Alternatively, this connection can be made in a sterile manner so as to be able to increase the storage time of the inactivated plasma prior to its transfusion.

The plasma is transferred, via the first and second tubes 16, 18, from the bag to the inactivation bag 3 via the container 4 containing the virucidal substance 2.

When the plasma passes through the container 4, the latter dissolves the tablet of virucidal substance 2 so that the inactivation bag 3 contains plasma containing virucidal substance 2.

To this end, at least one dissolving agent can be added to the tablet of virucidal substance 2 so as to improve its solubilization by the plasma.

Then, an inactivation treatment is implemented, for example by irradiating the fluid contained in the inactivation bag 3 with light radiation, so as to inactivate any viruses.

Then the inactivated fluid is transferred, via the third and fourth pipes 19, 21, from the inactivation bag 3 to the collection bag 6 via the filter 7 so as to remove the virucidal substance 2 from the fluid.

The collection bag 6 thus contains the inactivated plasma which is devoid of virucidal substance 2. Then, the collection bag 6 can be separated from the bag system 1, for example by cutting and sealing the fourth tubing 21, so that the collection bag 6 can be used, possibly after a storage time, directly in an arranged system to transfuse its contents to a patient.

Claims

1. Pouch system (1) for viral inactivation, in a closed circuit, of a biological fluid using a virucidal substance (2), of the type comprising an inactivation pocket (3) in fluid communication on the one hand with a container (4) containing the virucidal substance (2) and on the other hand with an inlet orifice (5) of a collection bag (6) via a filter (7) capable of eliminating the virucidal substance (2), said system (1) being characterized in that it comprises a first tube (16) provided at its upstream end (16a) with means (17) arranged to allow introduction into the system (1) biological fluid to be inactivated, said tube (16) being connected, by its downstream end (16b), directly to an inlet orifice (12) of the container (4).

2. Pouch system according to claim 1, characterized in that the container (4) is arranged in the vicinity or in an inlet orifice (5) of the inactivation pocket (3).

3. Bag system according to claim 1 or 2, characterized in that the filter (7) is arranged in an outlet compartment (23) of the inactivation bag (3).

4. bag system according to claim 1, characterized in that it further comprises: - a second tube (18) whose downstream end (18b) is connected to an inlet orifice (5) of the bag d '' inactivation (3) and whose upstream end

(18a) is connected to an outlet orifice (13) of the container (4) containing the virucidal substance (2);

- a third tube (19) whose upstream end (19a) is connected to an outlet orifice (9) of the inactivation bag (3) and whose downstream end

(19b) is connected to an inlet port (20) of the filter (7); - a fourth tube (21) whose upstream end (21a) is connected to an outlet orifice (22) of the filter (7) and whose downstream end (21 b) is connected to an inlet orifice (5 ) of the collection pocket (6).

5. Pouch system according to any one of claims 1 to 4, characterized in that the virucidal substance (2) comprises methylene blue supplemented with mannitol and / or polyol and / or leucine as well as at minus a dissolving agent.

6. Bag system according to any one of claims 1 to 5, characterized in that the filtering medium (14) is produced from at least one hydrophilic material in the form of a porous nonwoven and / or d '' a porous membrane capable of absorbing and / or adsorbing the virucidal substance (2).

7. Method for implementing a bag system (1) according to any one of claims 1 to 6, said method providing the successive stages of:

- Introducing into the bag system (1) the fluid to be inactivated by means (17) arranged to allow this introduction; - passing the fluid into the inactivation bag (3) via the container (4) so that the inactivation bag (3) contains the fluid containing the virucidal substance (2);

- apply to the fluid contained in the inactivation bag (3) radiation capable of inactivating any viruses it contains; - pass the fluid through the collection bag (6) via the filter (7) so that the fluid transferred into the collection bag (6) is inactivated and devoid of virucidal substance (2).

8. Method according to claim 7, characterized in that, after the transfer of the fluid in the collection bag (6), said collection bag (6) is dissociated from the bag system (1), for example by cutting and sealing the fourth tube (21).

9. Method according to claim 7 or 8, characterized in that it is applied to viral inactivation of blood or of a blood component previously leukoreduced.

10. Method according to claim 9, characterized in that the blood component is plasma.