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GB2642397A - Method for manufacturing viral vaccines and compositions thereof - Google Patents

Method for manufacturing viral vaccines and compositions thereof

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Publication number
GB2642397A
GB2642397A GB2515823.9A GB202515823A GB2642397A GB 2642397 A GB2642397 A GB 2642397A GB 202515823 A GB202515823 A GB 202515823A GB 2642397 A GB2642397 A GB 2642397A
Authority
GB
United Kingdom
Prior art keywords
cell line
virus
present
concentration
freeze
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Pending
Application number
GB2515823.9A
Inventor
Mhalasakant Dhere Rajeev
Balwant Vaidya Vivek
Ganpatrao Muley Ravindra
Laxman PATIL Sanjay
Vasudeo PANSE Arvind
Shrimantrao Jadhav Ramakant
Hanamant BHOSALE Jayant
Soli Poonawalla Cyrus
Cyrus Poonawalla Adar
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Serum Institute of India Pvt Ltd
Original Assignee
Serum Institute of India Pvt Ltd
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Serum Institute of India Pvt Ltd filed Critical Serum Institute of India Pvt Ltd
Publication of GB2642397A publication Critical patent/GB2642397A/en
Pending legal-status Critical Current

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A61K9/141—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers
    • A61K9/145—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers with organic compounds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K39/12—Viral antigens
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K39/12—Viral antigens
    • A61K39/155—Paramyxoviridae, e.g. parainfluenza virus
    • A61K39/165—Mumps or measles virus
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K39/12—Viral antigens
    • A61K39/20—Rubella virus
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K39/12—Viral antigens
    • A61K39/21—Retroviridae, e.g. equine infectious anemia virus
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A61K9/19—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles lyophilised, i.e. freeze-dried, solutions or dispersions
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K2039/51—Medicinal preparations containing antigens or antibodies comprising whole cells, viruses or DNA/RNA
    • A61K2039/525—Virus
    • A61K2039/5254—Virus avirulent or attenuated
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K2039/54—Medicinal preparations containing antigens or antibodies characterised by the route of administration
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K2039/545—Medicinal preparations containing antigens or antibodies characterised by the dose, timing or administration schedule
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K2039/57—Medicinal preparations containing antigens or antibodies characterised by the type of response, e.g. Th1, Th2
    • A61K2039/575—Medicinal preparations containing antigens or antibodies characterised by the type of response, e.g. Th1, Th2 humoral response
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K2039/70—Multivalent vaccine
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    • C12N2760/00011—Details
    • C12N2760/18011—Paramyxoviridae
    • C12N2760/18411—Morbillivirus, e.g. Measles virus, canine distemper
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    • C12N2760/00011—Details
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    • C12N2760/00011—Details
    • C12N2760/18011—Paramyxoviridae
    • C12N2760/18711—Rubulavirus, e.g. mumps virus, parainfluenza 2,4
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    • C12N2760/00011—Details
    • C12N2760/18011—Paramyxoviridae
    • C12N2760/18711—Rubulavirus, e.g. mumps virus, parainfluenza 2,4
    • C12N2760/18761—Methods of inactivation or attenuation
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    • C12N2770/00011—Details
    • C12N2770/36011—Togaviridae
    • C12N2770/36211—Rubivirus, e.g. rubella virus
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    • C12N2770/00011—Details
    • C12N2770/36011—Togaviridae
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    • C12N2770/00011—Details
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    • C12N2770/36211—Rubivirus, e.g. rubella virus
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Abstract

Present invention provides a method of producing clarified virus pool of virus to obtain a lyophilized/freeze-dried live attenuated virus immunogenic composition/ formulation comprising atleast one or more than one antigens/immunogens. Present invention provides a method of producing a clarified virus pool of viruses such as measles, mumps, rubella. It provides the improved large scale affordable /safe manufacturing processes (encompassing cultivation, purification & formulation stages) that utilize minimum animal origin components, provide high virus yield, ensure virus integrity/stability preservation across manufacturing & storage.

Claims (73)

1. WE CLAIM:
2. 1. A method of producing a clarified virus pool, the method comprising: a. providing a cell line in a cell media, a buffer and a supplement; b. treating cells of the cell line with at least one enzyme; c. infecting the cell line with a virus to form an infected cell line; d. washing of the infected cell line with a virus media and the buffer; e. harvesting the infected cell line in the media to obtain a harvest; optionally re- harvesting the infected cell line one or more times; f. adding at least one stabilizer to the harvest; and g. clarifying the harvest to obtain a clarified virus pool (CVP). optionally, the cell line or the infected cell line in exponential growth phase is - grown with additional ventilation or aeration, or - provided with re-addition of the buffer or - both.
3. 2. The method as claimed in claim 1, wherein the virus is selected from single-stranded, positive-sense, negative-sense, enveloped, non-enveloped RNA viruses belonging to the family Picornaviridae, Caliciviridae, Togaviridae, Matonaviridae, Flaviviridae, Coronaviridae, Retroviridae, Filoviridae, Bunyaviridae, Rhabdoviridae, Orthomyxoviridae, Arenaviridae, Paramyxoviridae.
4. 3. The method as claimed in claim 1 or 2, wherein the virus is single-stranded, negative- sense, enveloped, RNA viruses belonging to the family Paramyxoviridae and single- stranded, positive-sense, enveloped, RNA viruses belonging to the family Matonaviridae.
5. 4. The method as claimed in any one of the claims 1 to 3, wherein the virus is Measles morbillivirus (measles virus), Mumps orthorubulavirus (mumps virus) and Rubivirus rubellae (rubella virus).
6. 5. The method as claimed in any one of the claims 1 to 4, wherein the cell line is selected from animal cell line, mammalian, avian, insect cell line, human cell line, primary cell line, diploid cell line, continuous cell line, Rhesus monkey kidney (RhMK) cells; Primary rabbit kidney cells; Human foreskin fibroblasts; Chick embryo fibroblast (CEF); Human epidermoid carcinoma cells (HEp-2); Human lung carcinoma cells (A549); Human Cervix Epithelial (HeLa); African Green Monkey Kidney Epithelial (Vero); Human Lung Fibroblast (MRC-5); Human Lung Fibroblast (MRC-9); Mouse Embryo Fibroblast (NIH3T3); Mouse Connective Tissue Fibroblast (L929); Chinese Hamster Ovary Fibroblast (CHO); Syrian Hamster Kidney Fibroblast (BHK-21); Human embryo Kidney Epithelial (HEK-293); Human Liver Epithelial (HepG2); Bovine Aorta Endothelial (BAE-1); Human Neuroblastoma Neuronal (SH-SY5Y); Mouse Myeloma Lymphoblast (NS0); Human Hystiocytic Lymphoma Lymphoblast (U937); Human Leukemia Lymphoblast (HL60); Mouse B-cell Lymphoma Lymphoblast (WEHI231); Mouse Lymphoma Lymphoblast (YAC1); Human Myeloma Lymphoblast (U266B1); Human T- cell Leukemia Lymphoblast (Jurkat); Human Monocyte Leukemia Lymphoblast (THP-1); Human embryonic lung cells (W1-38); Madin Darby canine kidney cells (MDCK); Human embryonic retinal cells (PER.C6); Human embryonic retinoblasts (HER.911); Murine non-secreting myeloma (Sp2.0); Epithelial cells of African green monkey kidney origin (BSC-1 cells); Rhesus Monkey Kidney Epithelial Cells (LLC-MK2 cells); Cercopithecus aethiops monkey kidney cells (CV-1 cells); African green monkey kidney fibroblast-like cells (COS-cells); Crandell- Rees Feline Kidney Cells (CRFK cells); Rapidly Accelerated Fibrosarcoma cells (RAF cells); Normal Rabbit Kidney Epithelial Cells (RK-13 cells); Transformed C3H Mouse Kidney-1 (TCMK-1 cells); Pig Kidney Epithelial Cells (LLC-PK1 cells); Porcine kidney cells (PK15 cells); Rabbit kidney cell line (LLC-RK1 cells), Nonsecreting myeloma cell lines (NS-1 cells), New human male diploid cell strain (TIG-1, TIG-7); nonhuman primate diploid cell line (FRhL-2); Human foetal lung (IMR-90, IMR-91) cells; human diploid lung fibroblasts and others.
7. 6. The method as claimed in any one of the claims 1 to 5, wherein the cell line is selected from Human Lung Fibroblast (MRC-5) cell line and Chick embryo fibroblast (CEF) cell line.
8. 7. The method as claimed in any one of the claims 1 to 6, wherein the enzyme is selected from trypsin, recombinant trypsin, dipase, collagenase, hyaluronidase, elastase, cysteine protease, deoxyribonuclease I and chymotrypsin.
9. 8. The method as claimed in any one of the claims 1 to 7, wherein the cell media includes basal media, enriched media, selective and indicator media, transport media, storage media, carbon sources, or combination thereof.
10. 9. The method as claimed in any one of the claims 1 to 8, wherein the supplement includes amino acids, cholesterol, proteins, lactoferrin, linoleic acid, yeast extracts, serums, antioxidants, vitamins, antibiotics, nutrients, trace elements, adherence agents, extension factors, or combinations thereof.
11. 10. The method as claimed in any one of the claims 1 to 9, wherein the buffer is selected from the NaHCO3, NaOH, NaCl, HEPES, PIPES, MES, phosphates, carbonates, Hank’s, Earl’s or combinations thereof.
12. 11. The method as claimed in any one of the claims 1 to 10, wherein the virus media for washing the infected cell line is selected from basal media, enriched media, selective and indicator media, transport media, storage media, carbon sources, or combination thereof.
13. 12. The method as claimed in any one of the claims 1 to 11, wherein the washing of the infected cell lines by the virus media is performed post infection with virus having MOI in the range of 1:5 to 1: 60 and is followed by incubation at 30 to 40°C.
14. 13. The method as claimed in any one of the claims 1 to 12, wherein the at least one stabilizer includes at least one carbohydrate, at least one protein, at least one amino acid, or a combination thereof.
15. 14. The method as claimed in any one of the claims 1 to 13, wherein the clarification of the harvest is carried out using filters, preferably the filters are of material of construction selected from modified PVDF, cellulose acetate, polyethersulfone, polypropylene.
16. 15. The method as claimed in any one of the claims 1 to 14, wherein the clarification of the harvest is carried out using at least one filter having pore size in the range of 0.1 to 10.0 µ.
17. 16. The clarified virus pool (CVP) obtained by the method as claimed in any one of the claims 1 to 15.
18. 17. The method as claimed in any one of the claims 1 to 16, for producing a measles clarified virus pool, the method comprising: a. providing the cell line in a cell media, the buffer and the supplement; b. treating cells of the cell line with the enzyme; c. infecting the cell line with Measles morbillivirus to form the measles infected cell line; d. washing of the measles infected cell line with the virus media and the buffer; e. harvesting the measles infected cell line in the media to obtain the harvest; optionally re-harvesting the measles infected cell line; f. adding the stabilizer to the harvest; and g. clarifying the harvest to obtain the measles clarified virus pool (CVP). optionally, wherein the cell line or the measles infected cell line in exponential growth phase is - grown with additional ventilation or aeration, or - provided with re-addition of the buffer or - both.
19. 18. The method as claimed in claim 17, wherein the cell line is Human Lung Fibroblast (MRC-5) cell line.
20. 19. The method as claimed in any one of the claims 17 or 18, wherein the enzyme is recombinant trypsin.
21. 20. The method as claimed in any one of the claims 17 to 19, wherein the cell media is Minimum Essential Medium.
22. 21. The method as claimed in any one of the claims 17 to 20, wherein the supplement includes glutamine and foetal bovine serum.
23. 22. The method as claimed in claim 21, wherein foetal bovine serum is in the range 5% to 15%.
24. 23. The method as claimed in claim any one of the claims 17 to 22, wherein the virus media is Minimum Essential Medium.
25. 24. The method as claimed in any one of the claims 17 to 23, wherein the buffer comprises of sodium bicarbonate added to virus media and the buffer is in the range 0.5 to 4.0 g/L to maintain optimal pH of 6 to 8.
26. 25. The method as claimed in any one of the claims 17 to 24, wherein the measles virus includes Edmonston strain, including the Schwartz, the Edmonston-Zagreb, the Moraten strains; CAM-70; TD 97; Leningrad-16; AIK-C strain and Shanghai 191 (Ji-191) strains.
27. 26. A measles clarified virus pool (CVP) obtained by the method as claimed in any one of claims 17 to 25.
28. 27. The method as claimed in any one of the claims 1 to 16 for producing a mumps clarified virus pool, the method comprising: a. providing the cell line in the cell media, the buffer and the supplement; b. treating cells of the cell line with the enzyme; c. infecting the cell line with the Mumps orthorubula virus to form a mumps infected cell line; d. washing of the mumps infected cell line with the virus media and the buffer; e. harvesting the mumps infected cell line in the media to obtain the harvest; optionally re-harvesting the mumps infected cell line; f. adding the stabilizer to the harvest; and g. clarifying the harvest to obtain the mumps clarified virus pool (CVP). optionally, wherein the cell line or the mumps infected cell line in exponential growth phase is - grown with additional ventilation or aeration, or - provided with re-addition of the buffer or - both.
29. 28. The method as claimed in claim 27, wherein the cell line is Chick embryo fibroblast (CEF) cell line.
30. 29. The method as claimed in claim 27 or 28, wherein the enzyme is recombinant trypsin.
31. 30. The method as claimed in any one of the claims 27 to 29, wherein the cell media is Minimum Essential Medium.
32. 31. The method as claimed in any one of the claims 27 to 30, wherein the supplement includes glutamine, foetal bovine serum, and neomycin sulphate.
33. 32. The method as claimed in claim 31, wherein foetal bovine serum is in the range 5% to 15%.
34. 33. The method as claimed in any one of the claims 27 to 32, wherein the virus media is Minimum Essential Medium.
35. 34. The method as claimed in any one of the claims 27 to 33, wherein the buffer is sodium bicarbonate added to virus media and the buffer is in the range 0.5 to 4.0 g/L to maintain optimal pH of 6 to 8.
36. 35. The method as claimed in any one of the claims 27 to 34, wherein the virus includes Jeryl-Lynn, RIT 4385, Leningrad-3, Leningrad-Zagreb (L-Zagreb), Urabe Am9, Hoshino strain, Torii strain and S79 Rubini strains.
37. 36. A mumps clarified virus pool (CVP) obtained by the method as claimed in any one of the claims 27 to 35.
38. 37. The method as claimed in any one of the claims 1 to 16 for producing a rubella clarified virus pool, the method comprising: a. providing the cell line in the cell media and the supplement; b. treating cells of the cell line with the enzyme; c. infecting the cell line with the Rubivirus rubellae to form a rubella infected cell line; d. washing of the rubella infected cell line with the virus media and the buffer; e. harvesting the rubella infected cell line in the media to obtain the harvest; optionally re-harvesting the rubella infected cell line; f. adding the stabilizer to the harvest; and g. clarifying the harvest to obtain the rubella clarified virus pool (CVP). optionally, wherein the cell line or the rubella infected cell line in exponential growth phase is - grown with additional ventilation or aeration, or - provided with re-addition of the buffer or - both.
39. 38. The method as claimed in claim 37, wherein the cell line is Human Lung Fibroblast (MRC-5) cell line.
40. 39. The method as claimed in claim 37 or 38, wherein the enzyme is recombinant trypsin.
41. 40. The method as claimed in any one of claims 37 to 39, wherein the cell media is Minimum Essential Medium.
42. 41. The method as claimed in any one of the claims 37 to 40, wherein the supplement includes glutamine, foetal bovine serum, neomycin sulphate or combination thereof.
43. 42. The method as claimed in claim 41, wherein foetal bovine serum is in the range 5% to 15%.
44. 43. The method as claimed in any one of the claims 37 to 42, wherein the virus media is Minimum Essential Medium.
45. 44. The method as claimed in any one of the claims 37 to 43, wherein the buffer is sodium bicarbonate added to virus media and the buffer is in the range 0.5 to 4 g/L to maintain optimal pH of 6 to 8.
46. 45. The method as claimed in any one of the claims 37 to 44, wherein the virus includes Wister RA 27/3 strain, BRD-2 strain, Matsuba, DCRB19, Takahashi, Matsuura and TO- 336 strains.
47. 46. A rubella clarified virus pool (CVP) obtained by the method as claimed in any one of claims 37 to 45.
48. 47. A method of obtaining a lyophilized/ freeze-dried MMR immunogenic composition comprising at least one CVP selected from a measles CVP, a mumps CVP, a rubella CVP or a combination thereof, the method comprising: providing a measles CVP of claim 26 or obtained by any one of claims 17 to 25, a mumps CVP of claim 36 or obtained by any one of claim 27 to 35, a rubella CVP of claim 46 or obtained by any one of claims 37 to 45, or a combination thereof, blending of the CVPs, followed by lyophilizing the blended CVPs.
49. 48. The method as claimed in claim 47, wherein the method includes: a) thawing at least one CVP of measles, mumps, rubella virus or combination thereof at 30 to 35°C to obtain the thawed CVP; b) blending the thawed CVP and blind vaccine to obtain a blended solution; c) clarifying the blended solution through a 0.45µ filter to obtain a homogenous bulk; d) aseptically filling the homogenous bulk into sterilized vials, followed by transferring the vials to a lyophilizer/ freeze dryer. e) lyophilizing/ freeze drying the vials containing the homogenous bulk.
50. 49. The method as claimed in claim 48, wherein the lyophilizing/ freeze-drying step comprises: a) pre-freezing shelf, loading the trays containing vials of the MMR immunogenic composition on the shelf; b) freezing; c) primary drying/ sublimation and d) secondary drying
51. 50. A lyophilized/ freeze-dried MMR immunogenic composition obtained by the method as claimed in claim 49, the composition comprising; a) atleast one virus; b) stabilizer comprising atleast one carbohydrate, atleast one amino acid and atleast one hydrolyzed protein.
52. 51. The lyophilized/ freeze-dried MMR immunogenic composition as claimed in claim 50, comprising of live attenuated measles virus present at a dose of not less than 1000 CCID50 per dose, live attenuated mumps virus present at a dose of not less than 5000 CCID50 per dose and live attenuated rubella virus present at a dose of not less than 1000 CCID50 per dose.
53. 52. The lyophilized/ freeze-dried MMR immunogenic composition as claimed in claim 50, comprising of atleast one carbohydrate selected from a group consisting of natural carbohydrate, synthetic carbohydrate, monosaccharides, disaccharides, trisaccharides, oligosaccharides, reducing sugar, non-reducing sugar, sugar alcohols, polyol, polyhydroxyl compounds, chemically modified carbohydrates and glass transition facilitating agents which include sucrose, mannitol, trehalose, mannose, raffinose, lactitol, lactobionic acid, glucose, maltulose, iso- maltulose, maltose, lactose sorbitol, dextrose, fructose, glycerol, sorbitol, and fucose and a combination thereof.
54. 53. The lyophilized/ freeze-dried MMR immunogenic composition as claimed in claim 50, comprising of atleast one amino acid selected from a group consisting of tricine, leucine, iso-leucine, L-histidine, glycine, glutamine, L-arginine, L-arginine hydrochloride, lysine, L-alanine, Tryptophan, Phenylalanine, Tyrosine, Valine, Cysteine, Glycine, Histidine, Methionine, Proline, Serine, Threonine and a combination thereof.
55. 54. The lyophilized/ freeze-dried MMR immunogenic composition as claimed in claim 50, comprising of atleast one hydrolyzed protein obtained by chemical, enzymatic or thermal hydrolysis of protein from either plant or animal sources.
56. 55. The lyophilized/ freeze-dried MMR immunogenic composition as claimed in claim 50, comprising of at least one hydrolyzed protein selected from a group consisting of gelatin, lactalbumin hydrolysate, monosodium glutamate, collagen hydrolysate, keratin hydrolysate, peptides, Casein hydrolysate and whey protein hydrolysate.
57. 56. The lyophilized/ freeze-dried MMR immunogenic composition as claimed in claim 50, wherein the composition comprises; d) at least one carbohydrate at concentration range of 1-20% (w/v) e) at least one amino acid at concentration range of 0.01-10% (w/v); f) at least one hydrolyzed protein at concentration range of 0.1-10% (w/v)
58. 57. The lyophilized/ freeze-dried MMR immunogenic composition as claimed in claim 56, wherein at least one of the carbohydrate is sorbitol present at a concentration of 1 to 20% (w/v), 1 to 10% (w/v), preferably 3-6% (w/v).
59. 58. The lyophilized/ freeze-dried MMR immunogenic composition as claimed in claim 56, wherein at least one of the amino acid selected from a group consisting of tricine present at a concentration of 0.1% to 2% (w/v), L-histidine present at a concentration of 0.1% to 2% (w/v), L-alanine present at a concentration of 0.01% to 1% (w/v) and L-arginine hydrochloride present at a concentration of 0.1% to 5% (w/v).
60. 59. The lyophilized/ freeze-dried MMR immunogenic composition as claimed in claim 56, wherein atleast one of the hydrolysed protein selected from a group consisting of gelatin present at a concentration of 0.1% to 5% (w/v) and lactalbumin hydrolysate present at a concentration of 0.1% to 2% (w/v).
61. 60. The lyophilized/ freeze-dried MMR immunogenic composition as claimed in claim 50, comprising of an adjuvant selected from a group consisting of aluminum hydroxide, aluminum phosphate, aluminum hydroxyphosphate, and potassium aluminum sulfate or a mixture thereof.
62. 61. The lyophilized/ freeze-dried MMR immunogenic composition as claimed in claim 50, comprising of an immunostimulatory component selected from a group consisting of an oil and water emulsion, MF-59, a liposome, a lipopolysaccharide, a saponin, lipid A, lipid A derivatives, Monophosphoryl lipid A, 3–deacylated monophosphoryl lipid A, AS01, AS03, an oligonucleotide, an oligonucleotide comprising at least one unmethylated CpG and/or a liposome, Freund’s adjuvant, Freund’s complete adjuvant, Freund’s incomplete adjuvant, CRL-8300 adjuvant, muramyl dipeptide, TLR-4 agonists, flagellin, flagellins derived from gram negative bacteria, TLR-5 agonists, fragments of flagellins capable of binding to TLR-5 receptors, QS-21, ISCOMS, Chitosan, saponin combination with sterols and lipids.
63. 62. The lyophilized/ freeze-dried MMR immunogenic composition as claimed in claim 50, comprising of a pharmaceutically acceptable additive selected from a group consisting of transporter, excipient, binder, carrier, isotonic agent, emulsifier and humectant.
64. 63. The lyophilized/ freeze-dried MMR immunogenic composition as claimed in claim 50, wherein the excipient is selected from a group consisting of salt including NaCl, KCl, KH2PO4, Na2HPO4.2H2O, CaC12, and MgCl2; non-ionic surfactant including polysorbate 20, polysorbate 40, polysorbate 60, polysorbate 65, polysorbate 80, polysorbate 85, nonylphenoxypolyethoxethanol, octylphenoxypolyethoxethanol, oxtoxynol 40, nonoxynol- 9, triethanolamine, triethanolamine polypeptide oleate, polyoxyethylene- 660 hydroxystearate, polyoxyethylene- 35 ricinoleate, soy lecithin and a poloxamer - 0.001%- 0.05%; polymers including dextran, carboxymethylcellulose, hyaluronic acid ad cyclodextrin.
65. 64. The lyophilized/ freeze-dried MMR immunogenic composition as claimed in claim 50, wherein the lyophilized/freeze-dried viral vaccine composition is reconstituted with an aqueous solution selected from a group consisting of saline, buffer and WFI (water for injection).
66. 65. The lyophilized/ freeze-dried MMR immunogenic composition as claimed in claim 64, wherein the buffer is selected from a group consisting of sodium chloride, acetate, carbonate, citrate, lactate, gluconate, tartrate, phosphate buffer saline, borate, histidine buffer, succinate buffer, HEPES, TRIS and Citrate-phosphate.
67. 66. The lyophilized/ freeze-dried MMR immunogenic composition as claimed in claim 64, wherein the final pH of the reconstituted composition is in the range of pH 6.5 to 7.5.
68. 67. The lyophilized/freeze-dried MMR immunogenic composition as claimed in any one of the claims 50-66, comprising: a) live attenuated measles virus present at a dose of not less than 1000 CCID50 per dose, live attenuated mumps virus present at a dose of not less than 5000 CCID50 per dose and live attenuated rubella virus present at a dose of not less than 1000 CCID50 per dose; b) stabilizer comprising carbohydrate consisting of sorbitol present at a concentration of 1 to 10% (w/v); amino acid consisting of tricine present at a concentration of 0.1% to 2% (w/v), L- histidine present at a concentration of 0.1% to 2% (w/v), L-alanine present at a concentration of 0.01% to 1% (w/v) and L-arginine hydrochloride present at a concentration of 0.1% to 5% (w/v); and hydrolyzed protein consisting of gelatin present at a concentration of 0.1% to 5% (w/v) and lactalbumin hydrolysate present at a concentration of 0.1% to 2% (w/v).
69. 68. The lyophilized/freeze-dried MMR immunogenic composition as claimed in claim 67, comprising: a) live attenuated measles virus present at a dose of not less than 1000 CCID50 per dose, live attenuated mumps virus present at a dose of not less than 5000 CCID50 per dose and live attenuated rubella virus present at a dose of not less than 1000 CCID50 per dose; b) stabilizer comprising carbohydrate consisting of sorbitol present at a concentration of 5% (w/v); amino acid consisting of tricine present at a concentration of 0.3% (w/v), L-histidine present at a concentration of 0.21% (w/v), L-alanine present at a concentration of 0.1% (w/v) and L-arginine hydrochloride present at a concentration of 1.6% (w/v); and hydrolyzed protein consisting of gelatin present at a concentration of 2.5% (w/v) and lactalbumin hydrolysate present at a concentration of 0.35% (w/v).
70. 69. The lyophilized/freeze-dried MMR immunogenic composition as claimed in claim 68, wherein the lyophilized virus vaccine composition is in the form of a single dose composition or a multi-dose composition.
71. 70. The lyophilized/freeze-dried MMR immunogenic composition as claimed in claim 69, wherein the multi-dose composition additionally comprises preservative.
72. 71. A kit comprising the lyophilized/freeze-dried MMR immunogenic composition as claimed in claim 67 or 68 comprises; a) a first container containing a lyophilized (freeze-dried) viral vaccine composition said composition comprising: live attenuated measles virus present at a dose of not less than 1000 CCID50 per dose, live attenuated mumps virus present at a dose of not less than 5000 CCID50 per dose and live attenuated rubella virus present at a dose of not less than 1000 CCID50 per dose; carbohydrate consisting of sorbitol present at a concentration of 1 to 10% (w/v); amino acid consisting of tricine present at a concentration of 0.1% to 2% (w/v), L-histidine present at a concentration of 0.1% to 2% (w/v), L-alanine present at a concentration of 0.01% to 1% (w/v) and L-arginine hydrochloride present at a concentration of 0.1% to 5% (w/v); and hydrolyzed protein consisting of gelatin present at a concentration of 0.1% to 5% (w/v) and lactalbumin hydrolysate present at a concentration of 0.1% to 2% (w/v); and b) a second container containing an aqueous solution selected from saline or water for injection (WFI) for the reconstitution of the lyophilized (freeze-dried) vaccine composition.
73. 72. A kit comprising the lyophilized/freeze-dried MMR immunogenic composition as claimed in claim 67 or 68 comprises; a) a first container containing a lyophilized (freeze-dried) viral vaccine composition said composition comprising: live attenuated measles virus present at a dose of not less than 1000 CCID50 per dose, live attenuated mumps virus present at a dose of not less than 5000 CCID50 per dose and live attenuated rubella virus present at a dose of not less than 1000 CCID50 per dose; carbohydrate consisting of sorbitol present at a concentration 5% (w/v); amino acid consisting of tricine present at a concentration 0.3% (w/v), L-histidine present at a concentration 0.21% (w/v), L-alanine present at a concentration 0.1% (w/v) and L-arginine hydrochloride present at a concentration 1.6% (w/v); and hydrolyzed protein consisting of gelatin present at a concentration of 2.5% (w/v) and lactalbumin hydrolysate present at a concentration 0.35% (w/v); and b) a second container containing an aqueous solution selected from saline or water for injection (WFI) for the reconstitution of the lyophilized (freeze-dried) vaccine composition.
GB2515823.9A 2023-03-27 2024-03-27 Method for manufacturing viral vaccines and compositions thereof Pending GB2642397A (en)

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CN113373107A (en) * 2021-01-29 2021-09-10 上海生物制品研究所有限责任公司 Method for producing virus by preparing passage chick embryo cells in large scale
WO2023037387A2 (en) * 2021-09-08 2023-03-16 Serum Institute Of India Private Limited Freeze-dried viral combination vaccine compositions and process for preparation thereof

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* Cited by examiner, † Cited by third party
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IN202022019429A (en) * 2020-05-07 2021-02-05
CN113373107A (en) * 2021-01-29 2021-09-10 上海生物制品研究所有限责任公司 Method for producing virus by preparing passage chick embryo cells in large scale
WO2023037387A2 (en) * 2021-09-08 2023-03-16 Serum Institute Of India Private Limited Freeze-dried viral combination vaccine compositions and process for preparation thereof

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