Sterility Testing of Immonobiological Medicinal Products in Russia. Historical Background and Current Requirements

Sterility is one of the key parameters of biological safety of immunobiological medicinal products. The article traces the history  of the development of sterility test methods for immunobiological  medicinal products from as far back as 1961 and up to the current  requirements laid down in the State Pharmacopoeia of the Russian  Federation, 13th edition. The article provides a detailed analysis of  major approaches to the improvement of medicines quality  evaluation based on this parameter, namely to the choice of: optimal growth media and methods of their evaluation, sensitive test strains, incubation conditions, the number of test samples (i.e., sample size)  required for reliable demonstration of batch sterility; as well as  approaches to the development of a test design that would accommodate specific aspects of production and use of  immunobiological products. The article dwells upon the longstanding use of the sterility testing scheme developed in the national agency for control of immunobiological products — L.A. Tarasevich State  Institute for Standardization and Control of Medicinal  Immunobiological Products. The article analyses the current status of harmonisation of requirements for sterility testing of immunobiological products and other groups of medicines with those of the leading world pharmacopoeias, and prospects of using these requirements in the Eurasian Economic Union.

1. 1 . Federal Law, December 22, 2014, No. 429-FZ «On Amendments to the Federal Law «On Circulation of Medicines» (In Russ.)

2. Federal Law, September 17, 1998, No. 157-FZ «About the Immuno Prophylaxis of Infectious Diseases» (Revised July 18, 2011) (In Russ.)

3. Sanitary Regulations SR 3.3.2.015–94. «Production and Monitoring of Medical Immunobiological Products to Ensure Their Quality» (Approved by the Decision of the State Committee for Sanitary and Epidemiological Supervision of Russia of August 12, 1994) (In Russ.)

4. Rules for the Organization of Production and Quality Control of Medicinal Products (Approved by the Order of the Ministry of Industry and Trade of the Russian Federation of June 14, 2013, No. 916) (In Russ.)

5. The State Pharmacopoeia of the Russian Federation 12th ed. Part 1. Мoscow: SCEEMP; 2008 (In Russ.)

6. Microbiological Control of Sterility of Medicinal Products. Lecture 10 (In Russ.) Available from: http://www.gmpua.com/QC/Sterilitytesting.pdf

7. State Pharmacopoeia of the USSR 7th ed. Мoscow–Leningrad: Medgiz; 1934 (In Russ.)

8. WHO Technical Report Series, No. 530, 1975. 25 report (In Russ.)

9. State Pharmacopoeia of the USSR 9th ed. Moscow: Мedgiz; 1961 (In Russ.)

10. State Pharmacopoeia of the USSR 10th ed. Мoscow: Meditsina; 1968 (In Russ.)

11. Instructions for Controlling the Sterility of Vaccines, Anatoxins, Bacteriophages, Therapeutic Sera and Allergens (Approved by the Ministry of Health of the USSR, 1971) (In Russ.)

12. Bendas LG, Runova VF, Petrova IT, Raskin BM. Dehydrated Medium for Control of Sterility of Medical Biological Preparations. In: The Standards, Strains and Methods of Control of Viral, Bacterial Products and Allergens. Collection of Research Papers of MNIIVS im. I.I Mechnikova. Moscow; 1975. P. 266–70 (In Russ.)

13. Petrova IT, Rezepov FF. On the Possibility of Using a Single Nutrient Medium to Control the Sterility of Medical Biological Products. In: The Standards, Strains and Methods of Control of Viral and Bacterial Products. Collection of Research Papers of MNIIVS im. I.I. Mechnikova. Moscow; 1977. P. 186–92 (In Russ.)

14. Order of the Ministry of Health of the USSR of February 19, 1979, No. 192 «On Improving the Control of the Sterility of Bacterial and Viral Preparations». «Instructions for the Control of the Sterility of Vaccines of Anatoxins, Bacteriophages, Serum Preparations and Allergens» (In Russ.)

15. 39/<71>/2016. United States Pharmacopeia. 39th ed. Available from: http://www.uspnf.com/uspnf/login

16. European Pharmacopoeia 9.0. 2017. Available from: http://online6.edqm.eu/ep900

17. 2.2.11/6.0/2012. Indian Pharmacopoeia.

18. 4.06/XVII/2016. The Japanese Pharmacopoeia. 17th ed. Available from: http://jpdb.nihs.go.jp/jp17e/000217650.pdf

19. Order of the Ministry of Health of the USSR, January 13, 1983, No. 31 «On the Unification of Methods for the Control of Medical Immunobiological Preparations». Collection of Instructions on General Methods for Controlling Sterility, Physicochemical Properties, Pyrogenicity, Absence of Contaminants and Toxicity of Immunobiological Preparations (In Russ.)

20. Nutrient Medium for the Control of Medical Biological Preparations (Thioglycolic Medium), Dry. TU. 42.14.162–79 (In Russ.)

21. Petrova IT. Standardization of the Method of Sterility Control of Medical Biological Preparations. Cand. Biol. Sci [Thesis]. Мoscow; 1981 (In Russ.)

22. Gavristova IA, Andreeva ZM, Bendas LG. Author’s Certificate No. 990808 for an Invention «Method for Quality Control of a Thioglycolic Medium». Application No. 3311679 of July 3, 1981 (In Russ.)

23. FS 42-354ВС–90. Nutrient Medium for Sterility Control (Thioglycolic Medium) (In Russ.)

24. FS 42-3390–97. Nutrient Medium for Sterility Control (Thioglycolic Medium) (In Russ.)

25. Instructions for Use of the Nutrient Medium for Sterility Control, Dry (Thioglycolic Medium) Approved on December 29, 1990 (In Russ.)

26. State Pharmacopoeia of the USSR 11th ed. Publication 2. Moscow: Meditsina; 1989 (In Russ.)

27. VFS 42-1844-88. Test for Sterility (In Russ.)

28. Decree of the Government of the Russian Federation, December 18, 1995, No. 1241 «Concerning the State Control over Medical Immunobiological Preparations» (In Russ.)

29. Order of the Ministry of Healthcare of the Russian Federation and the State Committee for Sanitary and Epidemiological Supervision of the Russian Federation, March 4, 1996, No. 79/36 «On the Improvement of State Control Over Medical Immunobiological Preparations» (In Russ.)

30. Medunitsyn NV. Vaccinology. Moscow: Triada-X; 2010 (In Russ.)

31. Decree of the State Sanitary Epidemiological Service of the Russian Federation, June 3, 1994, No. 5 «On Introduction of System of the State Registration and Certification of Medical Immunobiological Preparations» (In Russ.)

32. МUK 4.1/4.2.588–96 «Testing of Injectable Medical Immunobiological Preparations» (Approved by the State Committee on Sanitary and Epidemiology Surveillance, October 31, 1996) (In Russ.)

33. Ozeretskovsky NA, Zatolochina KE, Snegireva II. Suggestions for Preventing Undesired Reactions at Application Immunobiological Medicinal Products in the Russian Federation. Safety and Risk of Pharmacotherapy 2015; (1): 25–9 (In Russ.)

34. The International Pharmacopoeia. 7th ed. 2017. Available from: http://apps.who.int/phint/en/p/docf/

35. Movsesyants AA, Bondarev VP, Olefir YuV, Merkulov VA, Shimchuk LF. Quality Standarts for Immunobiological Medicinal Products — New Texts in the State Pharmacopoeia of the Russian Federation. The Bulletin of the Scientific Centre for Expert Evaluation of Medicinal Products 2016; (2): 38–41 (In Russ.)

36. Order of the Ministry of Industry and Trade of the Russian Federation, October 23, 2009, No. 965 «On Approval of the Strategy for the Development of the Pharmaceutical Industry of the Russian Federation for the Period Until 2020» (In Russ.)

37. Federal Law of the Russian Federation, April 12, 2010, No. 61-FZ «On Circulation of Medicines» (As Amended by Federal Law No. 192-FZ of July 27, 2010, No. 271-FZ of October 11, 2010, No. 313-FZ of November 29, 2010) (In Russ.)

38. Lepakhin VK, Olefir YuV, Merkulov VA, Bunatyan ND, Romanov BK, Yavorsky AN, Rychikhina EM. The History of Creation and Development of the Control and Licensing System of Medicines in Russia. The Bulletin of the Scientific Centre for Expert Evaluation of Medicinal Products 2016; (1): 3–10 (In Russ.)

39. Sukhanova SM, Zaharova NE. Nutrient Media in the Practice of Microbiological Research. In: Guide to Medical Microbiology. Moscow: Binom; 2008. P. 221–54 (In Russ.)

40. Sukhanova SM, Berdnikova ZE, Zaharova NE. A New Approach to Trials of Drugs for Sterility. In: All-Russian Research-to-Practice Conference «Vaccinology-2010». Improvement of Immunobead and Logical Means of Prevention, Diagnosis and Treatment of Infectious Diseases. Moscow; 2010. P. 108 (In Russ.)

41. Order of the Ministry of Health of the Russian Federation, October 29, 2015, No. 771 «Approval of General Pharmacopeia Articles and Pharmacopeia Articles» (In Russ.)

42. General Monograph 1.2.4.0003.15 Sterility. The State Pharmacopoeia of Russian Federation 13th ed. V. 3. Moscow; 2015 (In Russ.) Available from: http://www.femb.ru/feml