Standardisation of human immunoglobulin preparations: Harmonising Russian State pharmacopoeia with world quality standards

INTRODUCTION. Human immunoglobulin preparations (HIP) used in medicine effectively treat autoimmune diseases, inflammatory diseases, and immune deficiencies and prevent diseases of various aetiologies. Harmonising Russian national quality standards (monograph and general pharmacopoeial monographs) for HIP with world quality standards is one of priorities for improving medical supply in Russia. Current quality standards for HIP need to be revised due to significant differences from the leading world pharmacopoeias in what regards quality assessment.

AIM. This study aimed to systematise and analyse national and international compendial quality control requirements for HIP as part of aligning Russian State  Pharmacopoeia  with  the world quality standards, in order to develop HIP monograph drafts.

DISCUSSION. 33 monographs for HIP have been analysed in several pharmacopoeias: 14 monographs in European Pharmacopoeia (Ph. Eur.) and British Pharmacopoeia (BP), 7 — in Indian Pharmacopoeia (IP), and 12 — in Chinese Pharmacopoeia (ChP). The study has shown the number of quality standards for HIP in certain regional and national pharmacopoeias. Ph. Eur., BP, and IP were found to have no general chapters for HIP, while ChP included 2 general chapters. Ph. Eur. and BP showed the highest number of monographs on specific HIP. Currently, United States Pharmacopoeia (USP) shows no monographs on HIP. Considering a recent trend towards harmonisation of national and regional compendial requirements, the authors have analysed HIP quality requirements from Russian State Pharmacopoeia and Ph. Eur., recognised as the basic pharmacopoeia. A comparative analysis of Russian quality standards has shown differences in very important quality parameters, e.g. prekallikrein activator, antibodies to hepatitis B surface antigen, immunoglobulin А (normal HIP for intramuscular and subcutaneous administration), and antibodies to hepatitis А virus (HIP for intramuscular administration). The study also showed the difference in the existing quality  assessment  approach,  and  the  resulting need to align Russian and international quality requirements for HIP, improve quality assurance, and unify control methods. The completed analysis of compendial quality requirements for HIP was used to prepare the drafts of the general chapter monographs on normal HIP as per administration.

CONCLUSIONS. Comparative analysis of compendial requirements shows the need to harmonise Russian quality standards for HIP with the leading world pharmacopoeias, primarily Eur. Pharm. The developed drafts of the monographs have been aligned with their counterparts around the world and include up-to-date methods of quality assessment. Further HIP standardisation requires new compendial references.

1. Wilson BE, Freman CM. Immunoglobulin therapy for immunodeficiency. Allergy Asthma Proc. 2024;45(5):364–70. https://doi.org/10.2500/aap.2024.45.240053

2. Mukhina AA, Abramova IN, Kuzmina NB, et al. Immunoglobulin replacement therapy in patients with primary immunodeficiency diseases in Russia. Pediatric Hematology/Oncology and Immunopathology. 2020;19(4):18–29 (In Russ.). https://doi.org/10.24287/1726-1708-2020-19-4suppl-18-29

3. Gröning R, Walde J, Ahlm C, et al. Intravenous immunoglobulin therapy for COVID-19 in immunocompromised patients: A retrospective cohort study. Int J Infect Dis. 2024;144:107046. https://doi.org/10.1016/j.ijid.2024.107046

4. Farrugia A, Bansal M, Marjanovic I. Estimation of the latent therapeutic demand for immunoglobulin therapies in autoimmune neuropathies in the United States. Vox Sang: 2021;117(2):208–19. https://doi.org/10.1111/vox.13134

5. Vasiliev TL, Starkina OV. Pooled human immunoglobulin preparations as immunomodulating drugs. Mol Biol. 2019;53(5):758–66. https://doi.org/10.1134/S002689841905015X

6. Zubkova NV. Biotechnological aspects of effective and safe processing of donor plasma: problems and prospects. Biological Products. Prevention, Diagnosis, Treatment. 2014;(1):4–10 (In Russ.). EDN: SSXZEB

7. Ghorbani J, Kompany-Zareh M, Tahmasebi E. Antibodies purification from human plasma using fractionation, chromatography and gel electrophoreses assisted by multivariate analysis of complimentary absorption and fluorescence spectra. J Chromatogr B Analyt Technol Biomed Life Sci. 2021;1167:122526. https://doi.org/10.1016/j.jchromb.2021.122526

8. Chepanov SV, Zainulina MS, Selkov SA. Clinical and immunological substantiation of the protocol for the use of plasmapheresis and intravenous immunoglobulins in pregnant women with antiphospholipid syndrome. Medical Immunology (Russia). 2025;27(1):35–44 (In Russ.). https://doi.org/10.15789/1563-0625-UOP-2893

9. Vakhlayrskaya SS, Kostyleva MN, Botkina AS, et al. Practical aspects of the application of intravenous immunoglobulins for intravenous administration in various pathologies. Pediatria n.a. G.N. Speransky. 2021;100(2):174–81 (In Russ.). EDN: IFYDHG

10. Yarutkin AV, Bagirova VL. State Pharmacopoeia of the Russian Federation edition XV: development priorities. Regulatory Research and Medicine Evaluation. 2024;14(5):572–9 (In Russ.). https://doi.org/10.30895/1991-2919-2024-14-5-572-579

11. Kornilova OG, Bagirova VL. Pharmacopoeial standardisation of biological medicinal products: Basic principles for the common pharmaceutical market of the Eurasian Economic Union Economic Union. Biological Products. Prevention, Diagnosis, Treatment. 2025;25(1):72–82 (In Russ.). https://doi.org/10.30895/2221-996X-2025-25-1-71-82

12. Ustinnikova OB, Shcherbachenko IM, Kolesnikova ON, et al. Issues of physicochemical quality assessment of immunobiological medicinal products in the context of formation of a regulatory system in the Eurasian Economic Union. Journal Biomed. 2024;20(3E):117–28 (In Russ.). https://doi.org/10.33647/2713-0428-20-3E-117-128