Human plasma in the production of medicinal products: national differences in terms of harmonization with global compendial requirements

INTRODUCTION. Plasma-derived medicinal products (PDMPs) are used to treat a number of systemic diseases, immunodeficiency disorders, and life-threatening conditions.  The  growing PDMP consumption necessitates the scaling of production and the provision of a stable supply of plasma, with the quality meeting international standards.

AIM. This study aimed to systematize and analyze national and international compendial requirements for the quality of human plasma, including that used for PDMP production, within harmonization process of national requirements with global quality standards for the development of draft pharmacopeial monographs.

DISCUSSION. Analyzed regulatory documents and scientific literature revealed that plasma donation rates per donor ranged from 24 to 104 times per year in various countries, while acceptable donation volumes ranged from 650 to 850 mL. A two-stage donor selection system based on the results of two consecutive laboratory tests ensures high viral safety of medicinal products, which complies with international standards, including those of Plasma Protein Therapeutics Association. In the Russian Federation, the mandatory quarantine period for human blood plasma is 120 days. In the United States, plasma producers have voluntarily implemented a 60-day plasma quarantine protocol for further production. In France, plasma quarantine also lasts for two months. Analyzed viral safety control and assurance of individual donations, minipools, and fractionation pools (FPs) for viral markers in the national and regional quality standards revealed different approaches to standardization. The European and Indian Pharmacopoeias require testing of individual plasma donations for antibodies to HIV-1 and HIV-2, hepatitis C virus (HCV), and HBsAg. The US Code of Federal Regulations requires testing of individual plasma donations for HBsAg, antibodies to HIV-1, HIV-2, HCV, and HIV and HCV nucleic acids. The State Pharmacopoeia of the Russian Federation (SP RF) requires testing of each individual plasma donation for HBsAg, antibodies to HCV, HIV-1 p24 antigen, antibodies to HIV-1 and HIV-2, and the Treponema pallidum. As part of harmonizing SP RF with the monographs of foreign pharmacopoeias, requirements were established for the quality of human plasma, including that used for PDMP production.

CONCLUSIONS. The results of a comparative analysis of national and international quality requirements for fractionated plasma and virus-inactivated human plasma indicate the need to develop modern approaches to standardization and quality control. Draft pharmacopoeial monographs Human plasma for fractionation and Human virus-inactivated plasma have been prepared.

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