Excipients in biological medicinal products: Functional classification, stability issues, and analytical quantitation approaches

INTRODUCTION. When developing and evaluating new biological products (BP), potential adverse action and complicated analytical procedure are a specific issue. Innovative analytical methods and selection of excipients allow for risk minimisation and enhanced quality control of biological products. AIM. This study aimed to analyse modern quantitative approaches to BP excipients and assess their prospects in improving laboratory expertise during authorisation and quality compliance testing of a biological product that has been launched into the commercial market. DISCUSSION. The literature search was performed using SciFinder, PubMed, and eLIBRARY.RU databases. The authors showed data on functional classification of the excipients. Potential adverse effects were analysed, including sucrose nephropathy when using intravenous immunoglobulin preparations containing sucrose; hypoglycaemia; changes in amino acid metabolism; decreased DNA and RNA synthesis, and inhibition of platelet function caused by elevated sodium caprylate in albumin preparations. Analysed methods are based on excipient degradation. Possible solutions have been described (reduction or replacement with another excipient, such as sodium caprylate excluded from the BPs of many manufacturers). Innovative search approaches were used for new adjuvants (MF59, АS01, АS03, AS04, and RC-529) combining immune response inducers and delivery systems. The described mathematical model was used to select excipient composition. The authors analysed literature covering analytical methods for excipient quantitation, including liquid and gas-liquid chromatography and spectrophotometric quantitation methods of the most significant excipients in BPs (amino acids, polysorbates, phenol, phenoxyethanol, benzyl alcohol, and sodium caprylate). Prospects of different analytical techniques were considered (size-exclusion HPLC for evaluation of polysorbate 80, HILIC HPLC for selective quantitation of amino acid components, hydrophilic HPLC with refractometric detection and ion-exchange HPLC with amperometric detection for selective quantitation of carbohydrate stabilisers (sorbitol, mannitol, trehalose, glucose, lactose, sucrose, maltose), as well as gas-liquid chromatography for 2-phenoxyethanol and m-cresol. CONCLUSIONS. Selecting BP excipients is a complex task that requires a control strategy not only for established concentrations, but also for products of possible degradation. Developing unified analytical methods for excipient quantitation is a priority for quality assurance of BPs authorised and launched into the commercial market.