The Integrated Model of Quality Management System of Laboratory Studies of Medicines (Review)

Introduction. The publication is devoted to the role of laboratory research in ensuring the quality of domestic medicines and is a review and analysis of regulatory documents and current publications on this topic.

Text. A number of different types of laboratories are involved in Drug life cycle and ensuring their effectiveness and safety. Today there are a large number of regulations governing laboratory research. Common to all types of laboratories and regulatory documents is the need to organize an effective quality management system (QMS) for the drug life cycle laboratories. The aim of this review is to analyze approaches to regulating the quality of laboratory research of domestic drugs and to consider the most effective QMS model, which is fundamental for all types of laboratories in the life cycle of drugs.

Conclusion. The laboratory research quality system serves as a basic tool for achieving the ultimate goal - the clinical value of drugs and is designed to ensure that risks for patients are minimized. At the same time, each stage of the drug life cycle provides a solution to a specific problem on the way to this goal, which must be taken into account when building a QMS in each type of laboratory. The range of regulatory documents and external assessment systems (accreditation, certification, inspection control, etc.) in the field of domestic laboratory research is quite diverse. In this regard, it is advisable for the laboratory to build a harmonious QMS based on priorities in accordance with the goals and objectives. The most effective method for building such a system is an integrated management system model.

1. Federal'nyy zakon Rossiyskoy Federatsii № 184-FZ ot 27.12.2002 "O tekhnicheskom regulirovanii" [Federal Law of Russian Federation № 184-FZ of 27 December 2002 "On Technical Regulation"]. Available at: http://www.consultant.ru/document/cons_doc_LAW_40241/ Accessed: 26.07.2021. (In Russ.)

2. SDA-06-2009 "Terminy i opredeleniya, ispol'zuemye v edinoy sisteme otsenki sootvetstviya v oblasti promyshlennoy, ekologicheskoy bezopasnosti, bezopasnosti v energetike i stroitel'stve" [System of documents for accreditation SDA-06-2009 "Terms and definitions used in the unified conformity assessment system in the field of industrial, environmental safety, safety in energy and construction"]. Available at: https://docs.cntd.ru/document/902356361. Accessed: 26.07.2021. (In Russ.)

3. SDA-15-2009. "Trebovaniya k ispytatel'nym laboratoriyam" [System of documents for accreditation SDA-15-2009. "Requirements for testing laboratories"] Available at: http://www.normacs.ru/Doclist/doc/VJFV.html. Accessed: 26.07.2021. (In Russ.)

4. GOST ISO/IEC 17025-2019 "Obshchie trebovaniya k kompetentnosti ispytatel'nykh i kalibrovochnykh laboratoriy" [State standard GOST ISO/IEC 17025-2019 "General requirements for the competence of testing and calibration laboratories"]. Available at: https://docs.cntd.ru/document/1200166732. Accessed: 26.07.2021. (In Russ.)

5. GOST ISO/IEC 17000-2012 "Otsenka sootvetstviya. Slovar' i obshchie printsipy" [State standard GOST ISO/IEC 17000-2012 "Conformity assessment. Vocabulary and general principles"]. Available at: https://docs.cntd.ru/document/1200100949. Accessed: 26.07.2021. (In Russ.)

6. Federal'nyy zakon Rossiyskoy Federatsii № 61-FZ ot 12.04.2010 "Ob obrashchenii lekarstvennykh sredstv" [Federal Law of Russian Federation № 61-FZ of 12.04.2010 "On the Circulation of Medicines"]. Available at: http://www.consultant.ru/document/cons_doc_LAW_99350/ Accessed: 26.07.2021. (In Russ.)

7. Reshenie Soveta Evraziyskoy ekonomicheskoy komissii ot 03.11.2016 № 81 "Ob utverzhdenii Pravil nadlezhashchey laboratornoy praktiki Evraziyskogo ekonomicheskogo soyuza v sfere obrashcheniya lekarstvennykh sredstv" [Decision of the Council of the Eurasian Economic Commission dated 03.11.2016 No. 81 "On approval of the Rules of good laboratory practice of the Eurasian Economic Union in the field of circulation of medicines"]. Available at: https://docs.cntd.ru/document/456026101. Accessed: 26.07.2021. (In Russ.)

8. Feofilova A. E., Foteeva A. V., Rostova N. B. The Modern Concepts of Pharmaceutical Development in the Context of the Transition to a Uniform Regulation of Medicinal Products Circulation. Razrabotka i registratsiya lekarstvennykh sredstv = Drug development & registration. 2020;9(4):171-179. (In Russ.) DOI: 10.33380/2305-2066-2020-9-4-171-179.

9. Rozhnova S. A., Tsypkina A. V. Analysis of the system organization of pharmaceutical drug development. Razrabotka i registratsiya lekarstvennykh sredstv = Drug development & registration. 2017;(3):170-176. (In Russ.)

10. Singh H., Khurana L. K., Singh R. Chapter 3. Pharmaceutical development. In: Pharmaceutical Medicine and Translational Clinical Research. London: Academic Press; 2018. P. 33-46.

11. Torres M. Challenges in implementing quality by design: An industry perspective. Bioprocess International. 2015. Available at: https://bioprocessintl.com/analytical/downstream-development/challenges-in-implementing-quality-by-design-an-industry-perspective/ Accessed: 26.07.2021.

12. Singh L., Sharma V. Quality by Design (QbD) approach in pharmaceuticals: status, challenges and next steps. Drug Delivery Letters. 2015;5(1):2-8.

13. Guideline I. C. H. H. T. Pharmaceutical Development Q8 (R2). Current step 4. 2009. Available at: https://database.ich.org/sites/default/files/Q8_R2_Guideline.pdf. Accessed: 26.07.2021.

14. Guideline I. C. H. H. T. Quality risk management Q9. Current step 4. 2005. Available at: https://database.ich.org/sites/default/files/Q9_Guideline.pdf. Accessed: 26.07.2021.

15. Guideline I. C. H. H. T. Pharmaceutical quality system Q10. Current Step 5. 2008. Available at: https://www.ema.europa.eu/en/documents/scientific-guideline/international-conference-harmonisation-technical-requirements-registration-pharmaceuticals-human_en.pdf. Accessed: 26.07.2021.

16. Lawrence X. Yu., Amidon G., Khan M. A., Hoag S. W., Polli J., Raju G. K., Woodcock J. Understanding pharmaceutical quality by design. The AAPS journal. 2014;16(4):771-783. DOI: 10.1208/s12248-014-9598-3.

17. Politis S. N., Colombo P., Colombo G., M. Rekkas D. M. Design of experiments (DoE) in pharmaceutical development. Drug development and industrial pharmacy. 2017;43(6):889-901. DOI: 10.1080/03639045.2017.1291672.

18. GOST 7.32-2017 SIBID "Otchet o nauchno-issledovatel'skoy rabote. Struktura i pravila oformleniya" [State standard GOST 7.32-2017SIBID "Report on research work. Structure and design rules"]. Available at: https://docs.cntd.ru/document/1200157208. Accessed: 26.07.2021. (In Russ.)

19. Bespalov A., Michel M. C., Steckler T. Good research practice in non-clinical pharmacology and biomedicine. Basingstoke: Springer Nature; 2020. 423 p.

20. Guillen J., Steckler T. Good Research Practice: Lessons from Animal Care and Use. Good Research Practice in Non-Clinical Pharmacology and Biomedicine. 2019:367-382. DOI: 10.1007/164_2019_292.

21. Aladysheva Zh. I., Belyaev V. V., Beregovykh V. V., Brkich G. E., Greybo S. V., Demina N. B., Dzhurko Yu. A., Ivanovskiy S. A., Nikolenko N. S., Komissarova V. A., Korsakov M. K., Lavrent'eva L. I., Meshkovskiy A. P., Miroshnikov A. E., Onegin S. V., Parfenov A. A., Pozdnyakov N. O., Poroykov V. V., Pyatigorskaya N. V., Pyatigorskiy A. M., Rakov A. A., Sidorov A. V., Spitskiy O. R., Trubnikov A. A., Khokhlov A. A., Khokhlov A. L., Chikina I. V., Shabalina M. M., Shabrov V. N., Shitov L. N., Yaichkov I. I. Promyshlennaya farmatsiya. Put' sozdaniya produkta [Industrial pharmacy. Product creation path]. Moscow: Rossiyskaya akademiya nauk; 2019. 393 p. (In Russ.)

22. GOST R ISO 9001-2015 "Sistemy menedzhmenta kachestva. Trebovaniya" [State standard GOST R ISO 9001-2015 “Quality management systems. Requirements"]. Available at: https://docs.cntd.ru/document/1200124394. Accessed: 26.07.2021. (In Russ.).

23. OECD series on principles of good laboratory practice and compliance monitoring-ENV/MC/CHEM-98-17. Organisation for Economic and Co-Operation Development-OECD. 1998. Available at: https://www.oecd.org/officialdocuments/publicdisplaydocumentpdf/?cote=env/mc/chem(98)17&doclanguage=en. Accessed: 26.07.2021.

24. Smirnov V. A., Goryachkin V. V., Shestakov V. N., Abramovich R. A. Guidelines for Promoting the Implementation of Pharmaceutical Quality Systems at EAEU Enterprises Through the Management of the Engagement of Production Personnel. Razrabotka i registratsiya lekarstvennykh sredstv = Drug development & registration. 2021;10(1):136-141. (In Russ.) DOI: 10.33380/2305-2066-2021-10-1-136-141.

25. Zaytseva M. A., Ivanov M. B., Verveda A. B., Lyanginen L. V. Risk Management in Preclinical Trials as Part of an Overall Integrated Quality Management System. Bezopasnost' i risk farmakoterapii = Safety and Risk of Pharmacotherapy. 2020;8(1):36-42. (In Russ.) DOI: 10.30895/2312-7821-2020-8-1-36-42.

26. Narkevich I. A., Flisyuk E. V., Shigarova L. V., Moskvin A. V. Rasprostranenie sistemy menedzhmenta kachestva na nauchnuyu deyatel'nost' [Extension of the quality management system to scientific activity]. Ekonomika kachestva. 2016;4(16):1-8. (In Russ.)

27. Narkevich I. A., Flisyuk E. V., Moskvin A. V., Shigarova L. V., Ivkin D. Yu., Ivkina A. S. Certification for the conformity of iso 9001 equirements as a first phase of implementation of good laboratory practice in the center of experimental pharmacology. Razrabotka i registratsiya lekarstvennykh sredstv = Drug development & registration. 2018;1:226-230. (In Russ.)

28. GOST 33044-2014 "Printsipy nadlezhashchey laboratornoy praktiki" [State standard GOST 33044-2014 "Principles of Good Laboratory Practice"]. Available at: https://docs.cntd.ru/document/1200115791. Accessed: 26.07.2021. (In Russ.)

29. GOST 31883-2012 "Printsipy nadlezhashchey laboratornoy praktiki (GLP). Obespechenie kachestva v sootvetstvii s Printsipami GLP" [State standard GOST 31883-2012 “Principles of Good Laboratory Practice (GLP). Quality assurance in accordance with the GLP Principles]. Available at: https://docs.cntd.ru/document/1200101517. Accessed: 26.07.2021. (In Russ.).

30. Burova E. D., Khodko S. V., Gushchina S. V., Makarova M. N., Makarov V. G. Risk management for quality assurance of preclinical research. Vedomosti Nauchnogo tsentra ekspertizy sredstv meditsinskogo primeneniya = The Bulletin of the Scientific Centre for Expert Evaluation of Medicinal Products. 2017;7(1):25-31. (In Russ.)

31. Knight L. A., Cree I. A. Quality assurance and good laboratory practice. Methods in Molecular Biology. 2011:115-124. DOI: 10.1007/978-1-61779-080-5_10.

32. Reshenie Soveta Evraziyskoy ekonomicheskoy komissii № 79 ot 3.11.2016 "Ob utverzhdenii Pravil nadlezhashchey klinicheskoy praktiki Evraziyskogo ekonomicheskogo soyuza" [Decision of the Council of the Eurasian Economic Commission No. 79 dated November 3, 2016 "On approval of the Rules for Good Clinical Practice of the Eurasian Economic Union"]. Available at: https://docs.cntd.ru/document/456026110. Accessed: 26.07.2021. (In Russ.)

33. Reshenie Soveta Evraziyskoy ekonomicheskoy komissii № 85 ot 3.11.2016 "Ob utverzhdenii Pravil provedeniya issledovaniy bioekvivalentnosti lekarstvennykh preparatov v ramkakh Evraziyskogo ekonomicheskogo soyuza" [Decision of the Council of the Eurasian Economic Commission No. 85 dated November 3, 2016 “On approval of the Rules for conducting bioequivalence studies of medicinal products within the framework of the Eurasian Economic Union”]. Available at: https://docs.cntd.ru/document/456026107. Accessed: 26.07.2021. (In Russ.)

34. Perspektivy razvitiya sistemy GLP v Rossii i EAES [Prospects for the development of the GLP system in Russia and the EAEU]. Available at: https://gxpnews.net/2020/10/perspektivy-razvitiya-sistemy-glp-v-rossii-i-eaes/ Accessed: 26.07.2021. (In Russ.)

35. Haidar S. H., Scheibner K. A. Bioanalytical Inspections: organizational changes and regulatory perspectives. Bioanalysis. 2016;8(10):999-1002. DOI: 10.4155/bio-2016-0052.

36. Kazey V. I. K voprosu ob obespechenii prozrachnosti i kontrolya KI/BE dzhenerikov. V sb.: Mezhdunarodnaya nauchno-prakticheskaya konferentsiya "Razrabotka i registratsiya lekarstvennykh sredstv. Issledovanie preparatov po pravilam EAES" [To the question of the danger of transparency and control of CI/BE of generics. In: International Scientific and Practical Conference “Development and Registration of Medicines. Research of drugs according to the rules of the EAEU"]. 6 December 2020. Moscow. 2020. (In Russ.).

37. Podpruzhnikov Yu. V. Provedenie bioanaliticheskikh issledovaniy v sootvetstvii s trebovaniyami GLP [Conducting bioanalytical research in accordance with the requirements of GLP]. Visnik farmakologii ta farmatsii. 2009;2:33-39. (In Ukrain.)

38. EMA Reflection paper for laboratories that perform the analysis or evaluation of clinical trial samples, EMA/INS/GCP/532137/2010. February 2012.

39. Khokhlov A. L., Lileeva E. G. Analysis of the quality of bioequivalence and pharmacokinetics studies in Russian Federation. Kachestvennaya klinicheskaya praktika. 2016;(2):64-70. (In Russ.)

40. Patel S., Huang Q. M., Jian W., Edom R., Weng N. Overview: Fundamentals of a Bioanalytical Laboratory. Handbook of LC-MS Bioanalysis. 2013:15-27. DOI: 10.1002/9781118671276.ch2.

41. Stevens W. Good clinical laboratory practice (gclp): the need for a hybrid of good laboratory practice and good clinical practice guidelines/standards for medical testing laboratories conducting clinical trials in developing countries. Quality Assurance. 2003;10(2):83-89. DOI: 10.1080/10529410390262727.

42. WHO Good Clinical Laboratory Practice (GCLP). Available at: https://www.who.int/tdr/publications/documents/gclp-web.pdf. Accessed: 26.07.2021.

43. Todd C. А., Sanchez A. М., Garcia A. Thomas N. Denny, Sarzotti-Kelsoe M. Implementation of Good Clinical Laboratory Practice (GCLP) guidelines within the External Quality Assurance Program Oversight Laboratory (EQAPOL). Journal of Immunological Methods. 2014;409:91-98. DOI: 10.1016/j.jim.2013.09.012.

44. GOST R ISO 15189-2009 "Laboratorii meditsinskie. Chastnye trebovaniya k kachestvu i kompetentnosti" [State standard GOST R ISO 15189-2009 "Medical laboratories. Particular requirements for quality and competence"]. Available at: https://docs.cntd.ru/document/1200077769. Accessed: 26.07.2021. (In Russ.)

45. GOST R ISO 53022 "Tekhnologii laboratornye klinicheskie. Trebovaniya k kachestvu klinicheskikh laboratornykh issledovaniy" [State standard GOST R ISO 53022 "Technologies for laboratory clinical cues. Requirements for the quality of clinical laboratory research"]. Part 1-4. Available at: https://docs.cntd.ru/document/1200068114. Accessed: 26.07.2021. (In Russ.)

46. GOST R ISO 53079-2008 "Tekhnologii laboratornye klinicheskie. Obespechenie kachestva klinicheskikh laboratornykh issledovaniy [State standard GOST R ISO 53079-2008 "Clinical laboratory technologies. Quality assurance of clinical laboratory research"]. Part 1-4. Available at: https://docs.cntd.ru/document/1200068744. Accessed: 26.07.2021. (In Russ.)

47. GOST R 53133.2-2008 "Tekhnologii laboratornye klinicheskie. Kontrol' kachestva klinicheskikh laboratornykh issledovaniy" [State standard GOST R 53133.2-2008 "Technologies for laboratory clinicalcues. Quality control of clinical laboratory tests"]. Part 1-4. Available at: https://docs.cntd.ru/document/1200072567. Accessed: 26.07.2021. (In Russ.)

48. Dolgikh T. I. The system of quality management in medical laboratory: the problematic issues of implementation of GOST RKS 9001-2008,GOST R ISO 15189-2009 and GOST R ISO 530792008. Klinicheskaya laboratornaya diagnostika = Russian Clinical Laboratory Diagnostics. 2013;4:49-51. (In Russ.)

49. Utarbaeva I. K., Tungishbaev M. Sistema menedzhmenta kachestva v kliniko-diagnosticheskikh laboratoriyakh [Quality management system in clinical diagnostic laboratories]. Vestnik Kazakhskogo Natsional'nogo meditsinskogo universiteta. 2015;4:364-365. (In Russ.)

50. Lyang O. V., Chernichuk O. V., Rysenkova E. Yu., Zhirova I. A., Kochetov A. G. Problems of quality management of laboratory tests in Russia. Laboratornaya sluzhba = Laboratory Service. 2017;6(2):33-37. (In Russ.)

51. Zadachi chetyrekh etapov instrumenta PVKL [Tasks of the four stages of the PVCL tool]. Available at: https://extranet.who.int/lqsi/ru/content/zadachi-chetyrekh-etapov-instrumenta-pvkl.

52. Upravlenie kachestvom [Quality control]. Available at: Available at: https://extranet.who.int/lqsi/ru/node/526. Accessed: 26.07.2021. (In Russ.)

53. Reshenie Soveta Evraziyskoy ekonomicheskoy komissii № 77 ot 03.11.2016 "Ob utverzhdenii Pravil nadlezhashchey proizvodstvennoy praktiki Evraziyskogo ekonomicheskogo soyuza" [Decision of the Council of the Eurasian Economic Commission № 77 dated 03.11.2016 "On Approval of the Rules of Good Manufacturing Practice of the Eurasian Economic Union"]. Available at: https://docs.cntd.ru/document/456026099. Accessed: 26.07.2021. (In Russ.)

54. Federal'nyy zakon RF № 2300-1 ot 07.02.1992 "O zashchite prav potrebiteley" [Federal Law of the Russian Federation № 2300-1 of 07.02.1992 "On Protection of Consumer Rights"]. Available at: http://www.consultant.ru/document/cons_doc_LAW_305/ Accessed: 26.07.2021. (In Russ.)

55. Pravila proizvodstva i kontrolya kachestva lekarstvennykh sredstv i sistema udostovereniya kachestva farmatsevticheskikh preparatov v mezhdunarodnoy torgovle [Rules for the production and quality control of medicines and the system of certification of the quality of pharmaceuticals in international trade]. Available at: https://apps.who.int/iris/handle/10665/101206. Accessed: 26.07.2021. (In Russ.)

56. WHO Technical Report Series No. 1003, 2017. Available at: https://www.who.int/medicines/areas/quality_safety/quality_assurance/expert_committee/WHO_TRS_1003_full-version.pdf?ua=1. Accessed: 26.07.2021.

57. WHO Technical Report Series, No. 957, 2010. Available at: https://www.who.int/medicines/publications/TRS957_2010.pdf. Accessed: 26.07.2021.

58. Hulebak K. L., Schlosser W. Hazard analysis and critical control point (HACCP) history and conceptual overview. Risk analysis. 2002;22(3):547-552. DOI: 10.1111/0272-4332.00038.

59. Shestakov V. N., Podpruzhnikov Yu. V. Chto takoe khorosho i chto takoe plokho v farmatsevticheskom proizvodstve [What is good and what is bad in pharmaceutical production]. Moscow: FBU «GILS i NP»; 2017. 180 p. (In Russ.)

60. Korcok D., Trsic-Milanovic N., Mitic B., Karadzic N. The importance of integrated management systems in pharmacy. Tehnika. 2020;75(1):120-124. DOI: 10.5937/tehnika2001120k.

61. Yaremchuk A. A., Aleksandrov A. V. Aktual'nost' vnedreniya integrirovannykh sistem menedzhmenta na farmpredpriyatiyakh [Relevance of the implementation of integrated management systems at pharmaceutical enterprises]. Remedium. 2007;7:37-39. (In Russ.)

62. DallingI. Integrated Management Definition. CQIIMSIG. 2007. N.2.1.

63. PAS B. S. Specification of common management system requirements as a framework for integration. 2012.

64. Aleksandrov A. V. Faktor sub'ektivnosti pri otsenke riska po kachestvu [The factor of subjectivity in assessing risk by quality]. Farmatsevticheskaya otrasl'. 2001;5(28):116-119. (In Russ.)

65. Kim J. H., Scialli A. R. Thalidomide: the tragedy of birth defects and the effective treatment of disease. Toxicological sciences. 2011;122(1):1-6. DOI: 10.1093/toxsci/kfr088.