Quality (Attributes) over quantity: Minimal essential quality attributes for determining antibody stability in postproduction handling stability studies

Abstract

Quality attributes (QAs) of monoclonal antibody (mAb) therapeutics can be jeopardized when exposed to stress factors during administration, potentially leading to patient safety risks. Therefore, strict product handling instructions are provided by the manufacturer. However, because of variations in available supplies and local guidelines, there is a need for broadened handling options in clinical setting, to improve logistics and reduce costs and shortages. Therefore 3rd parties (parties other than the manufacturer) have conducted postproduction handling stability studies (PHSS) to provide additional stability data for extended conditions. However, there is no QA standardization for PHSS, because relations between QAs and clinical outcomes are mostly unknown. In this review we present an overview of 31 PHSS by 3rd parties on mAb therapeutics. Products, extended conditions, and assessed QAs were evaluated. Much variance in studied QAs, used analytical techniques, and study comprehensiveness was found. However, a positive trend was observed that over time more and more studies confirm with industry standards. The need for consensus for necessary QAs is discussed. Finally, a proposal for shared responsibility for stability data is presented; manufacturers provide physicochemical stability data, and pharmacists ensure microbiological stability, for safe use of mAb products when alternative handling instructions are applied.