Method of obtaining thermostable dried vaccine formulations

Patent metadata

Field	Value
Publication number	US-9782470-B2
Application number	US-201415029060-A
Country	US
Kind code	B2
Filing date	Oct 13, 2014
Priority date	Oct 16, 2013
Publication date	Oct 10, 2017
Grant date	Oct 10, 2017

Abstract

This present invention relates to compositions and methods for stabilizing a dried vaccine formulations. In particular, the invention provides a method for producing a vaccine composition comprising the steps of providing an aqueous composition comprising a buffer, the vaccine components and between 17.5% w/w and 60% w/w of a non-polymeric sugar, freezing the composition, and applying microwave radiation under a pressure lower than atmospheric pressure in order to sublimate the composition and obtain a dried vaccine formulation. The invention also provides a product obtainable by this method.

First claim

What is claimed is:

1. A method for drying a vaccine composition comprising a virus or viral protein subunit or virus-like particles comprising the steps of:
a) providing an aqueous composition in a primary container comprising a buffer, the virus or viral protein subunit or virus-like particles, and between about 20% w/w and about 60% w/w of one or more non-polymeric sugars;
b) freezing the composition, thereby forming at least one frozen body comprising the buffer in frozen form; and
c) applying microwave radiation in a traveling wave format at a power in a range of between 0.5 and 8 KW/hr/Kg to the frozen body under a pressure below atmospheric pressure to produce a dried formulation.

2. The method according to claim 1 , wherein the composition is sublimated in less than 12 hours.

3. The method according to claim 1 , wherein the composition is sublimated in 3 to 8 hours.

4. The method according to claim 1 , wherein the pressure is in the range of 20 to 500 mTorr.

5. The method according to claim 4 , wherein the pressure is in the range of 20 to 200 mTorr.

6. The method according to claim 1 , wherein the temperature of the composition in step c) does not exceed 45° C.

7. The method according to claim 1 , wherein the temperature of the composition in step c) does not exceed 35° C.

8. The method according to claim 1 , wherein the amount of the sugar in the aqueous composition is chosen from the group that consists of the ranges 20-55% w/w, 20-50% w/w, 20-45% w/w, 25-45% w/w, 25-47.5% w/w, 25-40% w/w, 30-47.5% w/w, 30-40% w/w, 25-35% w/w or 27-30% w/w.

9. The method according to claim 1 , characterised in that the sugar comprises monomeric and/or dimeric molecules.

10. The method according to claim 9 , wherein the sugar is glucose, galactose, maltose, sucrose, trehalose, fructose, lactose, saccharose, mannitol, sorbitol, xylitol or a combination thereof.

11. The method according to claim 1 , wherein the vaccine is a combination vaccine.

12. The method according to claim 1 , wherein the vaccine is an enveloped virus vaccine.

13. The method according to claim 1 , wherein the primary container is selected from glass vial, resin vials, plastic vials, dual cartridge device, or foil-pouch based devices vaccine.

14. The method according to claim 1 , wherein the moisture content of the composition after drying is less than 6.0%.

15. The method according to claim 1 , wherein the dried product formed comprises the vaccine dispersed in a solid matrix of a non-polymeric sugar.

16. The method according to claim 1 , wherein the composition is flash frozen.

17. The method according to claim 12 , wherein the enveloped virus is live.

18. The method according to claim 12 , wherein the enveloped virus is selected from cytomegalovirus, herpes simplex virus, measles, mumps, respiratory syncytial virus, rotavirus, rubella, dengue and varicella.

19. The method according to claim 1 , wherein the ratio of power distribution between the first half cycle and total drying power is 15% to 50%.

20. The method according to claim 1 , wherein the ratio of power distribution between the first half cycle and total drying power is 15% to 30%.

Assignees

• Merck Sharp & Dohme

Inventors

• Bhambhani Akhilesh
• Evans Robert K
• Sinacola Jessica
• Jones Morrisa

Classifications

• A61K47/183

  Amino acids, e.g. glycine, EDTA or aspartame · CPC title

• A61K9/145

  with organic compounds · CPC title

• A61K9/0019

  Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner (non-active ingredients are additionally classified in A61K47/00) · CPC title

• C12N2710/20071

  Demonstrated in vivo effect · CPC title

• A61K2039/70

  Multivalent vaccine · CPC title