PACKAGING FOR A MEDICAMENT USED FOR INNOVATIVE THERAPY

Abstract

Disclosed is a product including: a) at least one substance selected from recombinant nucleic acids, single cells and single tissues, the compound being contained in a primary container; and b) a secondary container containing the primary container, the secondary container consisting of an insulating material. Also disclosed is a method for transporting a substance selected from recombinant nucleic acids, single cells and single tissues, which uses the product.

Claims

1-10. (canceled)

11. A product comprising: a) at least one substance chosen from recombinant nucleic acids, myoblasts, isolated mesenchymal stem cells, isolated hematopoietic stem cells and immunocompetent cells, said substance being present in a primary container; and b) a secondary container, in which the primary container present, said secondary container consisting of an insulating material, and said product being present in a tertiary container comprising a heat regulation unit.

12. The product as claimed in claim 11, wherein the insulating material constituting the secondary container is a polymer chosen from polypropylene, polytetrafluoroethylene, polyethylene, polycarbonate, polyethylene terephthalate, polyvinyl chloride, polyvinylidene fluoride and their mixtures.

13. The product as claimed in claim 11, wherein the primary container is chosen from a bag, a tube, a bottle, a vial, a syringe, a microtube and a well plate.

14. The product as claimed in claim 11, further comprising a temperature probee.

15. The product as claimed in claim 11, the product being coated with a layer of material resistant to X-rays.

16. The product as claimed in claim 11, wherein the primary and secondary containers are leaktight.

17. A process for the transportation of a substance chosen from recombinant nucleic acids, isolated cells and isolated tissues comprising the following stages: i) placing said substance in a primary container; ii) placing said primary container obtained in stage i) in a secondary container, and thus obtaining a product as claimed in claim 11; and iii) closing the secondary container obtained in stage ii), said product being present in a tertiary container comprising a heat regulation unit.

18. The product of claim 14, wherein the temperature probe is a wire temperature probe.

19. The product of claim 15, wherein the layer of material resistant to X-rays is a sheet of lead.

20. The product as claimed in claim 16, wherein the tertiary container is leaktight.

21. A process for the transportation of a substance chosen from recombinant nucleic acids, isolated cells and isolated tissues comprising the following stages: i) placing said substance in a primary container; ii) placing said primary container obtained in stage i) in a secondary container, and thus obtaining a product as claimed in claim 12; and iii) closing the secondary container obtained in stage ii), said product being present in a tertiary container comprising a heat regulation unit.

22. A process for the transportation of a substance chosen from recombinant nucleic acids, isolated cells and isolated tissues comprising the following stages: i) placing said substance in a primary container; ii) placing said primary container obtained in stage i) in a secondary container, and thus obtaining a product as claimed in claim 13; and iii) closing the secondary container obtained in stage ii), said product being present in a tertiary container comprising a heat regulation unit.

23. A process for the transportation of a substance chosen from recombinant nucleic acids, isolated cells and isolated tissues comprising the following stages: i) placing said substance in a primary container; ii) placing said primary container obtained in stage i) in a secondary container, and thus obtaining a product as claimed in claim 14; and iii) closing the secondary container obtained in stage ii), said product being present in a tertiary container comprising a heat regulation unit.

24. A process for the transportation of a substance chosen from recombinant nucleic acids, isolated cells and isolated tissues comprising the following stages: i) placing said substance in a primary container; ii) placing said primary container obtained in stage i) in a secondary container, and thus obtaining a product as claimed in claim 15; and iii) closing the secondary container obtained in stage ii), said product being present in a tertiary container comprising a heat regulation unit.

25. A process for the transportation of a substance chosen from recombinant nucleic acids, isolated cells and isolated tissues comprising the following stages: i) placing said substance in a primary container; ii) placing said primary container obtained in stage i) in a secondary container, and thus obtaining a product as claimed in claim 16; and iii) closing the secondary container obtained in stage ii), said product being present in a tertiary container comprising a heat regulation unit.

26. A process for the transportation of a substance chosen from recombinant nucleic acids, isolated cells and isolated tissues comprising the following stages: i) placing said substance in a primary container; ii) placing said primary container obtained in stage i) in a secondary container, and thus obtaining a product as claimed in claim 18; and iii) closing the secondary container obtained in stage ii), said product being present in a tertiary container comprising a heat regulation unit.

27. A process for the transportation of a substance chosen from recombinant nucleic acids, isolated cells and isolated tissues comprising the following stages: i) placing said substance in a primary container; ii) placing said primary container obtained in stage i) in a secondary container, and thus obtaining a product as claimed in claim 19; and iii) closing the secondary container obtained in stage ii), said product being present in a tertiary container comprising a heat regulation unit.

28. A process for the transportation of a substance chosen from recombinant nucleic acids, isolated cells and isolated tissues comprising the following stages: i) placing said substance in a primary container; ii) placing said primary container obtained in stage i) in a secondary container, and thus obtaining a product as claimed in claim 20; and iii) closing the secondary container obtained in stage ii), said product being present in a tertiary container comprising a heat regulation unit.

Description

EXAMPLE 1: TRANSPORTATION OF VACCINE

[0045] A biological substance, in the case in point a vaccine, is transported under different conditions.

[0046] The maintenance of the temperature is evaluated during the duration of the transportation.

Determination of the Time for the Fall in Temperature of a Product Stabilized at Ambient Temperature and Introduced into a Casing Equipped with a Temperature Regulating Unit, Everything being Placed in a Chamber Under the ST96A Profile

1-1 Tertiary Container (Casing)

[0047] Packaging: Casing R11

[0048] External dimensions: 394310521 mm

[0049] Working dimensions: 171267224 mm

[0050] Insulator: Polyurethane foam and VIP panels

[0051] Separators: a separator made of plastic fiber

1-2 Temperature Regulating Unit

[0052] Designation: Rigid Snowgam 10/05

[0053] Arrangement: individual

[0054] Number of packs: 1

[0055] Dimensions: 18014535 mm

[0056] Weight of the pack: 670 g

[0057] Designation: Rigid Snowgam 12/05

[0058] Arrangement: individual

[0059] Number of packs: 2

[0060] Dimensions: 23018035 mm

[0061] Weight of the pack: 890 g

[0062] Designation: TRU (Thermal Regulating Unit)

[0063] Arrangement: individual

[0064] Number: 1

[0065] Dimensions: 300200150 mm

[0066] Weight: 7.38 kg

2Measurement of the Temperature

[0067] Thermobuttons used and positions:

[0068] Thermobutton number: THB 03 Location: Ambient temperature

[0069] Thermobutton number: THB 08 Location: Product

[0070] Thermobutton number: THB 10 Location: Casing interior

3Test Conditions

[0071] Type of products: Empty syringe (primary container) placed in a cardboard packaging with dimensions of 4323133 mm.

[0072] The syringe is placed inside a polypropylene box with dimensions of 200190110 mm (secondary container). Kraft paper was placed around the vaccine in order to immobilize it.

4Conditions of Loading

[0073] Temperature: +21 (3 C.)

[0074] Arrangement of the Rigid Snowgam 10/05 pack: at the bottom at +5 C.

[0075] Arrangement of the Rigid Snowgam 12/05 packs: 1 on each long side at +5 C.

[0076] Arrangement of the TRU: on the top at 21 C.

[0077] Arrangement of the plastic fiber separator: between the TRU and the polypropylene box containing the product.

[0078] The R11 casing was charged with the different cold accumulators and also the TRU and the polypropylene box (with immobilization); everything being placed in the test chamber for 24 hours (first 24 hours of the profile). After these 24 hours, the casing was opened and the vaccine (stabilized at ambient temperature) was added to the load.

ST96A Profile:

[0079]

TABLE-US-00001 ST96A Temperature Duration +22 C. 3 H +28 C. 4 H +22 C. 9 H +28 C. 8 H +40 C. 4 H +28 C. 3 H +22 C. 9 H +25 C. 8 H +22 C. 3 H +28 C. 4 H +22 C. 9 H +28 C. 8 H +40 C. 4 H +28 C. 3 H +22 C. 9 H +25 C. 8 H

Conclusion

[0080] In this configuration, the temperature of a vaccine introduced at ambient temperature into the casing equipped with 1 Rigid Snowgam 10/05, 2 Rigid Snowgam 12/05 and 1 TRU reaches 8 C. after testing for 30 minutes.

[0081] Subsequently, the casing is capable of maintaining the vaccine between +2 C. and +8 C. for at least 96 hours in this configuration.

EXAMPLE 2: TEST OF VALIDATION OF THE INSULATING PROPERTIES OF THE SECONDARY CONTAINER WHEN EMPTY

[0082] The aim is to demonstrate that, at a very low temperature, the polypropylene packaging (i.e. secondary container) makes it possible to reduce the thermal impact which might potentially detrimentally affect the integrity of a substance chosen from recombinant nucleic acids, isolated cells and isolated tissues.

[0083] The other objective is to demonstrate that, after transportation, when the secondary packaging made of polypropylene has returned to ambient temperature, the latter slows down the rise in temperature and thus makes possible a more secure handling for the substance.

[0084] The test is as follows:

[0085] A polypropylene packaging is placed in a freezer <60 C. for 10 h. A probe A (probe of Sensitech TempTale 4 Dry Ice type, which makes possible measurements from +60 C. to 110 C.) is placed inside the packaging and another B (of the same type) is placed outside the packaging.

[0086] This test is carried out in a room having a temperature regulated at 23 C.

[0087] The test began on Apr. 17, 2014 at 18 h 51 and came to an end on Apr. 18, 2014 at 10 h 07.

Result:

The Probe A was Placed Inside the Packaging:

Fall in Temperature:

[0088] Maximum value: 22.5 C. at Apr. 17, 2014 18:51

[0089] Target freezing value: <60.0 C. at Apr. 17, 2014 18:59

[0090] Time for falling from the maximum value (ambient temperature) to the target freezing value (ambient temperature of the freezer): 8 minutes

Rise in Temperature:

[0091] Minimum value: 77.5 C. at Apr. 18, 2014 09:51

[0092] Value above 0 C. (2.6 C.) at Apr. 18, 2014 09:57

[0093] Maximum value: 22.9 C. at Apr. 18, 2014 10:07

[0094] Time for rising from the minimum value (ambient temperature of the freezer) to the maximum value (ambient temperature): 16 minutes

[0095] Time for rising from the minimum value (ambient temperature of the freezer) to the first value above 0 C.: 6 minutes

The Probe B was Placed Outside the Packaging:

Fall in Temperature:

[0096] Maximum value: 22.5 C. at Apr. 17, 2014 18:51

[0097] Target freezing value: <60.0 C. at Apr. 17, 2014 18:55

[0098] Time for falling from the maximum value (ambient temperature) to the target freezing value (ambient temperature of the freezer): 4 minutes

Rise in Temperature:

[0099] Minimum value: 77.9 C. at Apr. 18, 2014 09:51

[0100] Value above 0 C. (10.6 C.) at Apr. 18, 2014 09:54

[0101] Maximum value: 22.7 C. at Apr. 18, 2014 10:00

[0102] Time for rising from the minimum value (ambient temperature of the freezer) to the maximum value (ambient temperature): 9 minutes

[0103] Time for rising from the minimum value (ambient temperature of the freezer) to the first value above 0 C.: 3 minutes.

Conclusion:

[0104] It is found that the polypropylene packaging (secondary container) provides a more gentle fall in temperature and also a slower rise in temperature. Specifically, all the parameters are on average multiplied by two.

EXAMPLE 3: TEST OF VALIDATION OF THE INSULATING PROPERTIES OF THE SECONDARY CONTAINER

[0105] Two 50 ml Duran Schott flasks each filled with 25 ml of water are placed in a cold chamber in order to take the temperature.

[0106] The first flask is subsequently placed in an isothermal transportation bag and surrounded with two gel packs frozen beforehand to 80 C.

[0107] The second flask is first of all placed in the polypropylene packaging (secondary container) before being placed in an isothermal transportation bag and surrounded with two gel packs frozen beforehand to 80 C.

[0108] Each isothermal bag is equipped with a wire probe, one of which will be placed inside the isothermal packaging. The probes used are probes of Sensitech TempTale 4 Dry Ice type which make possible measurements from +60 C. to 110 C.

[0109] The isothermal packaging is placed beforehand in the cold chamber in order to also be at temperature.

[0110] The aim is to demonstrate that the polypropylene packaging makes it possible to reduce the impact of the excess freezing caused by gel packs which have been frozen too much placed in a refrigerated truck, which might potentially detrimentally affect the integrity of a substance chosen from recombinant nucleic acids, isolated cells and isolated tissues, or also distort the temperature reading during transportation.

Results:

[0111] The test began on 22/04/14 at 16 h 36 and came to an end on 23/04/14 at 9 h 33.

[0112] A much smaller fall in the temperature measured by the probe inside the polypropylene packaging is observed, in comparison with the temperature measured by the probe placed directly in the middle of the two gel packs.

[0113] The difference in fall in temperature is approximately 20 C.

[0114] This test allows it to be concluded that a polypropylene packaging placed between two gel packs frozen beforehand to 80 C. for 10 h and allowed to defrost for approximately 4 h inside an isothermal transportation bag makes it possible to provide maintenance of the temperature between +2 C. and +8 C. for approximately 13 h.

Conclusion:

[0115] It is found that the polypropylene packaging provides a much smaller fall in temperature than the same product not packaged in a polypropylene packaging.

EXAMPLE 4: TEST OF VALIDATION OF THE INSULATING PROPERTIES OF THE SECONDARY CONTAINER

[0116] This protocol is targeted at testing the progression and the conditions under which the withdrawn samples are transported. A buffer solution or water is used to simulate the tissues or cells withdrawn.

[0117] The objective of this report is to describe the transfer of tissues/cells between a hospital and the site of production of the innovative therapy medicament. With the aim of mimicking this transfer of withdrawn tissues/cells, two tests were carried out: [0118] one using a buffer of PBS formulation, on 6 May 2014, over a temperature of +34/+38 C.; [0119] the other using water, on 17 Sep. 2014, over a temperature of +34/+38 C.

[0120] On each occasion, the objective is to guarantee the integrity of the flask during the transportation, from the removal up to the delivery, at a controlled temperature.

Materials Used:

Buffer or Water:

[0121] The formulation buffer mimicking the withdrawn sample (first test) was prepared beforehand on the hospital site. A 50 ml Sarstedt tube containing this buffer was thus prepared and placed in an incubator at +37 C. on May 6, 14 at 10 h 00.

TABLE-US-00002 Sarstedt tube Name of the product PBS Description Formulation buffer Dimension d. 2 cm h. 10 cm Volume 50 ml Labeling NA

[0122] The water mimicking the withdrawn sample (second test) was prepared beforehand on the hospital site. A 50 ml Sarstedt tube containing this water was thus prepared and placed in an incubator at +37 C. of the Nantes University Hospital Center (UHC) on Sep. 17, 2014 at 10 h 00.

TABLE-US-00003 Sarstedt tube Description Water Dimension d. 2 cm h. 10 cm Volume 50 ml Labeling NA

External Packaging:

[0123] The external packaging is composed of a casing with packs.

[0124] This packaging was prepared in order to maintain a temperature of +34/+38 C.

Packaging Protocol:

[0125] The Sarstedt tube containing the PBS or the water is placed in a 95 kPa plastic bag with a capacity of 11 (secondary packaging), then in a polypropylene box (200190110 mm) and then in the external packaging (394310521 mm).

Probes:

[0126] Two probes were used for this transportation test: [0127] a probe incorporated in the packaging, programmed at +34/+38 C.; [0128] a Thermobutton probe programmed with a measurement interval of 3 min for recording. Temperature +34/+38 C.

[0129] The results of the first test are as follows:

TABLE-US-00004 Internal Time temperature Actions elapsed Date Hour [+34 C.; +38 C.] Starting probes 00:00:00 5 May 2014 09:00:00 23.2 C. Installation of the 01:51:00 5 May 2014 10:51:00 21.9 C. accumulators Rise in temperature 02:06:00 5 May 2014 11:06:00 34.1 C. Departure package 02:51:00 5 May 2014 11:51:00 37.6 C. Opening: Handling 05:24:00 5 May 2014 14:24:00 36.2 C. at point A Arrival package on 1 Day 6 May 2014 13:15:00 35.5 C. the hospital site 04:15:00 Opening: Addition 1 Day 6 May 2014 13:27:00 35.1 C. of the withdrawn 04:27:00 sample Departure package + 1 Day 6 May 2014 13:36:00 34.5 C. withdrawn sample 04:36:00 Arrival package + 2 Days 7 May 2014 12:15:00 35.4 C. withdrawn sample A 03:15:00 Opening: Recovery 2 Days 7 May 2014 14:45:00 35.4 C. of the withdrawn 05:45:00 sample Temperature < than 5 Days 10 May 2014 23:33:00 33.9 C. 34 C. 14:33:00 Index Internal Temperature ( C.) Specification [+34.0; +38.0] C. Maximum 37.8 C. Minimum 21.9 C. Mean during the transportation 35.5 C. [05 May 2014 10:51- 07 May 2014 14:45]

[0130] The tube arrived under good conditions and adhering to the set points for the temperatures during the transportation.

[0131] The results of the second test were as follows:

TABLE-US-00005 Internal Time temperature Actions elapsed Date Hour [+34 C.; +38 C.] Starting probes 00:00:00 16 Sep. 2014 11:18 36.1 C. Departure package: 00:06:00 16 Sep. 2014 11:24 36.3 C. Sofrigam to Ulis Opening: Handling 03:27:00 16 Sep. 2014 14:45 35.5 C. CfC Ulis Arrival package on 21:24:00 17 Sep. 2014 08:42 35.5 C. the site of the Nantes UHC Opening: Addition 1 Day 17 Sep. 2014 11:51 34.8 C. withdrawn sample 00:33:00 Nantes UHC Departure package + 1 Day 17 Sep. 2014 11:54 34.8 C. withdrawn sample 00:36:00 Nantes UHC Arrival packaging + 2 Days 18 Sep. 2014 12:36 35.4 C. withdrawn sample 01:18:00 CfC Ulis Opening: Recovery 2 Days 18 Sep. 2014 16:18 30.1 C. withdrawn sample 04:54:00 CfC Ulis Rise in temperature 2 Days 18 Sep. 2014 16:33 34.2 C. after closing 05:15:00 Temperature < than 6 Days 22 Sep. 2014 13:33 32.5 C. 34 C. 02:15:00 Index Internal Temperature ( C.) Specification [+34.0; +38.0] C. Maximum 37.8 C. Minimum 24.9 C. Mean during the transportation 35.5 C. [17 Sep. 2014 11:51- 18 Sep. 2014 16:18]

[0132] The tube arrived under good conditions and adhering to the set points for the temperatures during the transportation.

[0133] In conclusion, these transportation operations are in accordance: the material transported was maintained at a good temperature and for at least 48 h.