Implementation of modern quality management system requirements in the production management of reference standards for pharmaceuticals and medicine

Objective: To summarize current requirements for the quality management system (QMS) in the production of reference materials (RMs) for pharmaceutical and medical applications, as well as to assess the challenges and prospects of system implementation to ensure reliable quality control of medicinal products.

Material and methods. The study analyzed international and national regulatory documents, including ISO 9001, ISO/IEC 17025, ISO 17034 standards as well as good manufacturing practice (GMP) and good laboratory practice (GLP) guidelines. Experiences in QMS implementation at RMs manufacturing enterprises in Russia and abroad was examined. The research methodology was based on a comparative analysis of requirements and practical approaches to quality assurance.

Results. Ensuring RM production quality requires integration of the international standards ISO 9001, ISO/IEC 17025, ISO 17034, and GMP/GLP guidelines. Comparative analysis showed that the Russian quality system in RM production is gradually aligning with the global benchmarks through ISO-based accreditation and international cooperation, while retaining elements of state regulation. Promising directions for QMS development include further harmonization of international standards, digitalization of quality control, and differentiation of RMs to include new medicinal product types. All this necessitates development of novel methodology.

Conclusion. An effective QMS in RM production is a critical factor in ensuring the quality and safety of pharmaceutical products. Integration of ISO standards and GMP/GLP principles enables the production of reference materials with the required accuracy, stability, and traceability, recognized at the international level. Further improvement of the quality system will provide the industry with reliable reference materials and enhance confidence in quality control results both domestically and internationally.

1. European Commission. EudraLex – Volume 4 – Good Manufacturing Practice (GMP) guidelines. Available at: https://health.ec.europa.eu/medicinal-products/eudralex/eudralex-volume-4_en (accessed 12.02.2025).

2. OECD series on principles of good laboratory practice and compliance monitoring. Available at: https://ntp.niehs.nih.gov/sites/default/files/iccvam/suppdocs/feddocs/oecd/oecd_glpcm.pdf (accessed 12.02.2025).

3. Studenok V.V., Kremleva O.N. Reference materials in the system of metrological assurance of quantitative analysis. Industrial laboratory. Diagnostics of materials. 2019; 85 (1 (II)): 130–4 (in Russ.). https://doi.org/10.26896/1028-6861-2019-85-1-II-130-134.

4. Shchepochkina O.Y., Gegechkori V.I., Prokof’eva V.I., et al. Modern approaches to the development of standard samples of drugs. Khimiko-farmatsevticheskii zhurnal. 2020; 54 (7): 49–54 (in Russ.). https://doi.org/10.30906/0023-1134-2020-54-7-49-54.

5. Bessonov Yu.S., Kremleva O.N. National market of reference materials. Curreent state, problems, and development prospects. Part 1. Introduction. Development of the national market of reference materials. Measurement Standards. Reference Materials. 2017; 13 (3–4): 9–19 (in Russ.). https://doi.org/10.20915/2077-1177-2017-13-3-4-9-19.

6. Pankov A.N., Zyryanova I.N., Kremleva O.N., et al. The need and potential for import substitution of reference materials in the Russian Federation: analysis of data from the Federal Information Fund for Ensuring the Uniformity of Measurements. Measurement Standards. Reference Materials. 2024; 20 (1): 47–58 (in Russ.). https://doi.org/10.20915/2077-1177-2024-20-1-47-58.

7. Chepilo D.A., Gegechkori V.I., Shchepochkina O.Yu., et al. A complex approach to the determination of authenticity in the development of standard samples for ace inhibitors. Химико-фармацевтический журнал. 2022; 56 (4): 41–7. https://doi.org/10.30906/0023-1134-2022-56-4-41-47.

8. Trubacheva L.V.1, Didik M.V.1, Chernova S.P.1, Slobodina V.Sh. Standard samples. For the question about creation and attestation. Chemical Physics and Mesoscopy. 2010; 12 (4): 539–42 (in Russ.).

9. Gegechkori V.I., Shatilina A.A., Shulga N.A., et al. Application of the fluorimetry method for the determination of impurities in pancreatin in developing a reference standard. Khimiko-farmatsevticheskii zhurnal. 2022; 56 (11): 59–63 (in Russ.). https://doi.org/10.30906/0023-1134-2022-56-11-59-63.

10. Gegechkori V.I., Shatilina A.A., Shulga N.A., et al. Biological reference materials: topical issues of development and certification procedure. Measurement Standards. Reference Materials. 2023; 19 (3): 21–9 (in Russ.).

11. Shulga N.A., Gegechkori V.I., Gorpinchenko N.V., et al. Development of ketoprofen impurity A (1-(3-Benzoylphenyl)ethanone) as a certified reference material for pharmaceutical quality control. Pharmaceuticals. 2025; 18 (1): 59. https://doi.org/10.3390/ph18010059.

12.