Systematic approach to cross-contamination risk management in the production of medicinal products

Introduction. Good Manufacturing Practice (GMP) requires drug manufacturers to apply risk management principles in their operations. One of the main risks to the quality and safety of pharmaceuticals is cross-contamination. The introduction of a systematic approach to contamination risk management requires manufacturers to make a comprehensive assessment of both production processes and the organization of production sites (premises, equipment, systems, etc.). Therefore, the transition to the current GMP requirements for operating production sites may require significantly higher financial and labor costs than for projected production facilities.

Aim. Development of a scientifically based program and methodology for cross-contamination risk management for existing pharmaceutical industries, taking into account compliance with the harmonized GMP requirements of the Russian Federation and the EAEU and world practice.

Materials and methods. In the course of the study, methods of risk management, analysis and systematization of data and a process approach were used.

Results and discussion. The key aspects of the organization of the co-manufacturing of medicines are outlined. A step-by-step approach to risk management, involving a preliminary assessment of the conformity of a production organization with GMP requirements is described. The proposed scheme is aimed at ensuring the continuous functioning of the cross-contamination risk management process.

Conclusion. The presented risk management methodology aims to conduct a proper assessment of the risks of cross-contamination for multiproduct pharmaceutical enterprises. This technique allows to identify areas that need improvement to ensure compliance of manufacturing sites with GMP requirements, which ultimately contributes to improving the quality of medicines.

1. Ob utverzhdenii Pravil nadlezhashchey proizvodstvennoy praktiki: Prikaz Minpromtorga Rossii ot 14.06.2013 g. № 916 (s izmeneniyami na 18.12.2015 g.): zaregistrirovano v Minyuste Rossii 10.09.2013 № 29938 [On the approval of the Rules of Good Manufacturing Practice: Order of the Ministry of Industry and Trade of Russia dated 14.06.2013 No 916 (as amended on December 18, 2015): registered with the Ministry of Justice of Russia on September 10, 2013 No. 29938]. Available at: http://www.consultant.ru. Accessed: 18.08.2021. (In Russ.)

2. Podpruznikov Yu. V., Shestakov V. N. Review, characteristics and analysis of the last changes in the GMP requirements. Razrabotka i registratsiya lekarstvennykh sredstv = Drug development & registration. 2016;(3):202–218. (In Russ.)

3. Ob utverzhdenii Pravil nadlezhashchey proizvodstvennoy praktiki Evraziyskogo ekonomicheskogo soyuza: Reshenie Soveta Evraziyskoy ekonomicheskoy komissii ot 03.11.2016 № 77 [On approval of the Rules of Good Manufacturing Practice of the Eurasian Economic Union: Decision of the Council of the Eurasian Economic Commission dated 03.11.2016 No 77]. Available at: http://www.consultant.ru. Accessed: 18.08.2021. (In Russ.)

4. EudraLex Volume 4 EU Guidelines for Good Manufacturing Practice for Medicinal Products for Human and Veterinary Use. 2015. Available at: https://ec.europa.eu/health/documents/eudralex/vol-4_en. Accessed: 18.08.2021.

5. Sargent E. V., Flueckiger A., Lovsin Barle E., Luo W., Molnar L. R., Sandhu R., Weideman P. A. The Regulatory Framework for Preventing Cross-Contamination of Pharmaceutical Products: History and Considerations for the Future. Regulatory Toxicology and Pharmacology: RTP. 2016;79(1):S3–S10. DOI: 10.1016/j.yrtph.2016.05.029.

6. ICH guideline Q9 on quality risk management: EMA/CHMP/ICH/24235/2006 – 2015. Available at: https://ich.org/page/qualityguidelines. Accessed: 18.08.2021.

7. Prikaz Minpromtorga Rossii ot 12.12.2013 № 1997 "Ob utverzhdenii Rekomendatsiy po organizatsii proizvodstva i kontrolya kachestva lekarstvennykh sredstv" [Order of the Ministry of Industry and Trade of Russia dated December 12, 2013 No. 1997 "On approval of the Recommendations for the organization of production and quality control of medicines"]. Available at: http://www.consultant.ru. Accessed: 18.08.2021. (In Russ.)

8. ISPE Baseline® Guide: Volume 7 – Risk-Based Manufacture of Pharmaceutical Products (Risk-MaPP). Makati: International Society for Pharmaceutical Engineering; 2017. 178 p.

9. How safe is your process? The usual causes of pharmaceutical contamination. Pharmaceutical Technology. 2018. Available at: https://www.pharmaceutical-technology.com/powder-handling/causes-of-pharmaceutical-contamination. Accessed: 15.09.2021.

10. ICH guideline Q10 on pharmaceutical quality system EMA/CHMP/ICH/214732/2007 – 2008. Available at: https://ich.org/page/quality-guidelines. Accessed: 18.08.2021.

11. Spiridonova A. A., Khomutova E. G. The risk-oriented approach in the quality management system of an industrial enterprise: the problem of selecting the methods of risk management. Organizator proizvodstva = Organizer of Production. (In Russ.) 2017;25(2):92–100. DOI: 10.25065/1810-4894-2017-25-2-92-100.

12. GOST R 58771-2019 "Menedzhment riska. Tekhnologii otsenki riska" [GOST R 58771-2019 "Risk management. Risk Assessment Technologies"]. Moscow: Standartinform; 2020. 146 p. (In Russ.)

13. Spiridonova A. A., Rudakova V. A., Khomutova E. G. Quality risk management of immunobiological drug production under cultivation conditions. Biofarmatsevticheskiy zhurnal = Russian Journal of Biopharmaceuticals. 2019;11(4):54–60. (In Russ.) DOI: 10.17513/np.407.

14. Inspection of health based exposure limit (HBEL) assessments and use in quality risk management: AIDE-memoire PI 052-1. Secretariat of the Pharmaceutical Inspection Convention. 2020. Available at: http://www.picscheme.org. Accessed: 08.08.2021.