Reference standards for evaluating the potency of human immunoglobulin preparations: Literature review

INTRODUCTION. Pharmaceutical production uses reference standards as an integral part of metrological support for analytical methods. A systematic literature analysis on standardisa­tion of human immunoglobulin preparations, particularly specific and special-purpose ones, will allow evaluating the metrological support in the Russian Federation and identifying new approaches to obtaining and using reference standards to assess specific potency.

AIM. This study aimed to analyse published data on the range of reference standards used to evaluate potency of human immunoglobulins in the Russian Federation and abroad.

DISCUSSION. PubMed, eLIBRARY.RU, and ConsultantPlus® legal research system showed that the list of international reference standards includes Rh₀(D), hepatitis B, tetanus, staphylococcal and cytomegalovirus infections, rabies, and smallpox human immunoglobulins. No reference standard is available for human immunoglobulin against tick-borne encephalitis, since no specific human immunoglobulin is produced in the European Union. There is an absolute dependence on the import of international reference standards for assessing the potency of human hepatitis B, cytomegalovirus, and rabies immunoglobulins. Reference standards are typically obtained from ready-to-use batches of medicinal products and then stabilised, bottled under sterile conditions, and lyophilised. The Register of the State Pharmacopoeia of the Russian Federation includes reference standards for Rh0(D), anti-tetanus serum, and staphylococcal immunoglobulin. Unlike international reference standards, pharmacopoeial standards are produced as solutions, thus significantly reducing antibody stability. For pharmacopoeial reference standards, statistical uncertainty of the certified value is established in the Russian Federation; however, while certifying international reference standards, their certification is not obligatory. According to literature analysis, the key requirements for reference standards are stability and composition / properties similar to standardised preparations. Russian and foreign certification requirements of reference standards have certain differences. The number of Russian reference standards based on human immunoglobulin G is limited, since they are mostly obtained from horse blood serum.

CONCLUSIONS. Russian pharmaceutical industry shows a deficit of national reference standards used for assessing specific potency of human immunoglobulins and donor plasma for their production. Thus, such reference standards should be released as lyophilisates and certified in international units, with an evaluation of statistical uncertainty of the antibody content.

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