Quality of biopharmaceuticals: Comparability exercise and post-approval surveillance

Abstract

Biopharmaceuticals (including biosimilars) are defined as a class of biologicals where the active substance is produced in living cells through recombinant DNA technology. When regulating biopharmaceuticals, among other things, the quality, where determining and measuring quality attributes (QAs), is considered a key regulatory aspect. A subset of QAs is considered critical QAs (CQAs) because small differences in these may potentially influence clinical outcomes of the therapy in patient care when they fall outside the acceptable range and limit. Therefore, the thesis aimed to study the quality of biopharmaceuticals (including biosimilars) by providing insight into (1) the comparability of QAs with emphasis on the CQAs, and (2) post-approval quality-related surveillance and actions by regulatory authorities after these medicines have been approved for use. The thesis provides learning regarding post-approval changes and defects in the quality of biopharmaceuticals that could potentially influence patient care. Moreover, the thesis reflects on the potential implications and future directions of comparability of CQAs and post-approval quality surveillance for regulation, policy-making, and patient care. The thesis concluded that the comparison of biopharmaceuticals relies significantly on the comparability of CQAs and also articulates that detecting small differences in and the criticality of QAs are crucial for demonstrating comparability. In the future, we will work on questions about the possible effects of small differences in clinical outcomes for patient care. The studies in the thesis have also shown that safety and efficacy of biopharmaceuticals must go hand in hand with ensuring pharmaceutical quality. Post-approval follow-up, surveillance, and regulatory action where necessary remain essential building blocks of a trusted biopharmaceutical system.