Preview

Biological Products. Prevention, Diagnosis, Treatment

Advanced search

An experience of scaling and intensifying the industrial production of the Gam-COVID-Vac vector adenovirus vaccine in the limiting conditions of the pandemic

https://doi.org/10.30895/2221-996X-2022-22-4-382-391

Abstract

The COVID-19 pandemic has presented a global challenge to the health system. More than 200 years of world epidemiological experience since the first mass use of vaccines have convincingly shown that effective vaccines are the key tools in the fight against dangerous infectious diseases, especially epidemic and pandemic ones. In the context of a rapidly spreading pandemic of a new infectious agent, it is crucial not only to develop fundamentally new vaccines, but also to be able to quickly organise their large-scale production. In the Russian Federation, in 2020, a team of the National Research Centre for Epidemiology and Microbiology named after Honorary Academician N.F. Gamaleya developed an innovative vector vaccine, Gam-COVID-Vaс, for the prevention of coronavirus disease caused by the SARS-CoV-2 virus. A number of pharmaceutical companies faced the challenge of producing the vaccine. The aim of the study was to optimise the production technology of Gam-COVID-Vac for scaling and increasing the production capacity. In the course of the work, the authors established critical quality attributes of the product, optimised analytical methods for their control, identified poorly scalable technological stages, streamlined the technological process before its transfer to production, and modified non-scalable and technologically unfeasible stages. The work resulted in the launch of industrial-scale production of active pharmaceutical ingredients for both components of Gam-COVID-Vac, which made it possible not only to meet the critical need for COVID-19 immunoprophylaxis in the Russian Federation, but also to supply this vaccine to a number of foreign countries.

About the Authors

A. N. Morozov
Generium JSC
Russian Federation

Anton N. Morozov, Cand. Sci. (Biol.)

10 Testovskaya St, Moscow 123112



I. R. Yakhin
Generium JSC
Russian Federation

Ildar R. Yakhin, Cand. Sci. (Biol.)

10 Testovskaya St, Moscow 123112



N. V. Stratonova
Generium JSC
Russian Federation

Natalya V. Stratonova, Cand. Sci. (Biol.)

10 Testovskaya St, Moscow 123112



M. V. Kutskir
Generium JSC
Russian Federation

Maksim V. Kutskir, Cand. Sci. (Biol.)

10 Testovskaya St, Moscow 123112



D. A. Poteryaev
Generium JSC
Russian Federation

Dmitry A. Poteryaev, Cand. Sci. (Biol.)

10 Testovskaya St, Moscow 123112



R. A. Khamitov
Generium JSC
Russian Federation

Ravil A. Khamitov, Dr. Sci. (Med.), Professor

10 Testovskaya St, Moscow 123112



References

1. Logunov DY, Dolzhikova IV, Zubkova OV, Tukhvatulin AI, Shcheblyakov DV, Dzharullaeva, AS, et al. Safety and immunogenicity of an rAd26 and rAd5 vector-based heterologous prime-boost COVID-19 vaccine in two formulations: two open, non-randomised phase 1/2 studies from Russia. Lancet. 2020;396(10255):887–97. https://doi.org/10.1016/S0140-6736(20)31866-3

2. Logunov DY, Dolzhikova IV, Shcheblyakov DV, Tukhvatulin AI, Zubkova OV, Dzharullaeva AS, et al. Safety and efficacy of an rAd26 and rAd5 vector-based heterologous prime-boost COVID-19 vaccine: an interim analysis of a randomised controlled phase 3 trial in Russia. Lancet. 2021;397(10275):671–81. https://doi.org/10.1016/S0140-6736(21)00234-8

3. Mohammed AQ, Sunkari PK, Srinivas P, Roy AK. Quality by design in action 1: controlling critical quality attributes of an active pharmaceutical ingredient. Org Process Res Dev. 2015;19(11):1634–44. https://doi.org/10.1021/OP500295A

4. Stratonova NV, Lisov AS, Morozov AN, Tyupa DV, Khamitov RA. Methodological approaches to validation of therapeutic recombinant proteins production based on the Quality by Design Concept. Biopreparaty. Profilaktika, diagnostika, lechenie = BIOpreparations. Prevention, Diagnosis, Treatment. 2018;18(3):175–83. (In Russ.) https://doi.org/10.30895/2221-996X-2018-18-3-175-183

5. Zubkova OV, Ozharovskaia TA, Dolzhnikova IV, Popova O, Shcherbakov DV. Grousova DM, et al. Immunobiological agent for inducing specific immunity against severe acute respiratory syndrome virus SARS-CoV-2. WO2021002776A1; 2021.

6. Wissing S, Faust N, Scheer N. Overview: manufacturing adenoviral vectors at large scale: how to select the best process and cell line to avoid RCA formation. Gen Eng Biotech News. 2021;41(10):35. https://doi.org/10.1089/gen.41.10.12

7. Joe CCD, Jiang J, Linke T, Li Y, Fedosyuk S, Gupta G, et al. Manufacturing a chimpanzee adenovirus-vectored SARS-CoV-2 vaccine to meet global needs. Biotechnol Bioeng. 2022;119(1):48–58. https://doi.org/10.1002/bit.27945

8. Srivastava A, Mallela KMG, Deorkar N, Brophy G. Manufacturing challenges and rational formulation development for AAV viral vectors. J Pharm Sci. 2021;110(7):2609–24. https://doi.org/10.1016/j.xphs.2021.03.024

9. Kawka K, Wilton AN, Madadkar P, Medina MFC, Lichty BD, Ghosh R, Latulippe DR. Integrated development of enzymatic DNA digestion and membrane chromatography processes for the purification of therapeutic adenoviruses. Sep Purif Technol. 2021;254(1):117503. https://doi.org/10.1016/j.seppur.2020.117503


Supplementary files

Review

For citations:


Morozov A.N., Yakhin I.R., Stratonova N.V., Kutskir M.V., Poteryaev D.A., Khamitov R.A. An experience of scaling and intensifying the industrial production of the Gam-COVID-Vac vector adenovirus vaccine in the limiting conditions of the pandemic. Biological Products. Prevention, Diagnosis, Treatment. 2022;22(4):382-391. (In Russ.) https://doi.org/10.30895/2221-996X-2022-22-4-382-391

Views: 973


Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.


ISSN 2221-996X (Print)
ISSN 2619-1156 (Online)