Drying process
The present invention relates to a method of drying biological and other labile samples so that they can be preserved as a highly viscous liquid. The method involves the steps of preparing a preservation sample by dissolving/suspending an active agent in a solution of a stabilizing agent, subjecting the preservation sample to such temperature and pressure conditions that the preservation sample loses solvent by evaporation without freezing or bubbling to form a foam and removing solvent until the preservation sample dries to form a highly viscous liquid.
1. A method for preserving an active agent comprising the steps of:
a) preparing a preservation sample by dissolving or suspending active agent in a solution of a stabilizing agent comprising a polyol at a concentration of between 3.15% and 50% (w/v);
b) subjecting the preservation sample to a temperature condition and to a pressure condition below 30 mbar, such that the preservation sample loses solvent by evaporation without freezing or bubbling, thereby forming a viscous liquid,
wherein the active agent retains at least 40% of the antigenicity, activity, immunogenicity, or combination thereof, as compared to a reference sample that has not been subject to the evaporation process.
2. The method of claim 1 , further comprising the step of:
c) further subjecting the preservation sample to temperature and pressure conditions such that the viscous liquid dries to form a highly viscous liquid.
3. The method of claim 1 , comprising reducing the pressure to at least 2 mBars and no more than 20 mbars during step b).
4. The method of claim 1 , wherein the temperature external to the preservation sample is between 5° C. and 37° C. during step b).
5. The method of claim 2 , wherein the temperature external to the preservation sample is between 5° C. and 37° C. during step c).
6. The method of claim 2 , wherein the temperature external to the preservation sample is higher during step c) than it is in step b).
7. The method of claim 6 , wherein the temperature external to the preservation sample is increased to above 20° C. during step c).
8. The method of claim 2 , wherein the pressure is reduced in step c) compared to the pressure during step b).
9. The method of claim 8 , wherein the pressure is reduced to 1 mbar or below during step c).
10. The method of claim 1 , wherein step b) is completed in less than 4 hours.
11. The method of claim 2 , wherein steps b) and c) are completed in less than 12 hours.
12. The method of claim 1 , wherein the stabilizing agent comprises a glass forming polyol selected from the group of: glucose, maltulose, iso-maltulose, lactulose, sucrose, maltose, lactose, sorbitol, iso-maltose, maltitol, lactitol, palatinit, trehalose, raffinose, stachyose, melezitose, and dextran.
13. The method of claim 12 , wherein the stabilizing agent is sucrose.
14. The method of claim 12 , wherein the concentration of stabilizing agent is 5-10% (w/v).
15. The method of claim 1 , wherein the preservation sample comprises phenol red.
16. The method of claim 1 , wherein the preservation sample is dried in a container with a solvent repellent interior surface.
17. The method of claim 1 , wherein the active agent comprises a molecule selected from the group of: protein, peptide, amino acid, polynucleotide, oligonucleotide, polysaccharide, oligosaccharide, polysaccharide-protein conjugate, and oligosaccharide-protein conjugate.
18. The method of claim 1 , wherein the active agent comprises a biological system selected from the group of: cells, subcellular compositions, bacteria, viruses, virus components and virus like particles.
19. The method of claim 18 , wherein the active agent comprises IPV (inactivated polio virus).
20. The method of claim 18 , wherein the active agent comprises Haemophilus influenzae type b polysaccharide or oligosaccharide.
21. The method of claim 18 , wherein the active agent comprises Neisseria meningitidis C polysaccharide or oligosaccharide.
22. The method of claim 1 , wherein the active agent comprises a vaccine.
23. A composition obtained by the method of claim 1 , comprising a highly viscous liquid comprising an active agent and a glass forming polyol stabilizing agent wherein the composition comprises a solvent content of less than 15% (w/w).
24. The composition of claim 23 , wherein the active agent retains at least 40% of the antigenicity, activity, inimunogenicity, or combination thereof, as compared to a reference sample that has not been subject to the evaporation process.
25. The composition of claim 23 , comprising a glass forming polyol selected from the group of: glucose, maltulose, iso-maltulose, lactulose, sucrose, maltose, lactose, sorbitol, iso-maltose, maltitol, lactitol, palatinit, trehalose, raffinose, stachyose, melezitose, and dextran.
26. The composition of claim 25 , wherein the glass forming polyol is sucrose.
27. The composition of claim 23 , wherein the active agent comprises a molecule selected from the group of: protein, peptide, amino acid, polynucleotide, oligonucleotide, polysaccharide, oligosaccharide, polysaccharide-protein conjugate, and oligosaccharide-protein conjugate.
28. The composition of claim 23 , wherein the active agent comprises a biological system selected from the group of: cells, subcellular compositions, bacteria, viruses, virus components, and virus like particles.
29. The composition of claim 23 , wherein the active agent comprises a vaccine.
30. The composition of claim 23 , wherein the active agent comprises IPV.
31. The composition of claim 23 , wherein the active agent comprises a bacterial polysaccharide or oligosaccharide.
32. The composition of claim 31 , wherein the active agent comprises a Haemophilus influenzae b polysaccharide or oligosaccharide.
33. The composition of claim 23 , wherein the active agent comprises a Neisseria meningitidis serogroup C polysaccharide or oligosaccharide.
34. The composition of claim 23 , held within a container with a solvent repellent interior surface.
35. An immunogenic composition or vaccine comprising the composition of claim 23 , and a pharmaceutically acceptable excipient.
36. A method of making a vaccine comprising the step of reconstituting the composition of claim 23 , in an aqueous solution.
37. The method of claim 36 , wherein the aqueous solution comprises a mixture of acellular or whole cell Diphtheria antigen, Tetanus antigen and Pertussis antigens.
38. The method of claim 37 ,wherein the vaccine comprising the mixture of acellular or whole cell Diphtheria antigen, Tetanus antigen and Pertussis antigens is at least in part adjuvanted with aluminium hydroxide.
39. A kit comprising the composition of claim 23 , held in a first container and a liquid vaccine component held in a second container.
40. The composition of claim 31 , wherein the polysaccharide or oligosaccharide is conjugated to a carrier protein.
41. The method of claim 1 , wherein the stabilizing agent is present at a concentration of between 3.15% and 25% (w/v).