Biological medicines (biologics) have made substantial contributions to the treatment of many chronic and serious diseases such as cancers, chronic inﬂammatory diseases and some rare genetic disorders, and are expected to provide signiﬁcant therapeutic beneﬁts to many patients who would otherwise have had limited treatment options.
Development of biosimilars or follow-on biologics is therefore an undeniable reality. However, biologics (other than blood products and vaccines) are relatively recent in origin and are beyond the reach of many patients due to their high price. Additionally, unlike a generic chemical drug, a follow-on biologic is similar but not exactly identical to the reference product, and this poses unique challenges in its development and regulatory approval process. Biological drugs are large therapeutic proteins and are enormously complex in structure. Their manufacture requires complicated biological production and puriﬁcation processes in highly controlled environmental conditions and under strict quality controls. A slight difference in the biological starting material (such as a genetically modified cell line or organism) or a minor change in a step in the manufacturing/purification process can have a significant impact on the quality and purity of the product, and may result in a product with appreciably different characteristics and a variable efficacy and safety profile as compared to the reference innovator product.
Pharmacovigilance is the Key
Post-approval pharmacovigilance is extremely important for biosimilars due to the nature of conditions they treat and the fact that fewer patients are exposed to a biologic during developmental clinical trials. In addition, because biologics are complex proteins which may stay longer in the body and undergo modifications through biological pathways, safety concerns for the molecules are likely to manifest at variable periods which may be outside of the time course of controlled clinical trials. Hence, safety profile of a biologic is not fully elucidated when it is first approved.
Since a biosimilar drug is not identical to the reference innovator product, the efficacy and safety data generated for the latter cannot be directly and completely transferred to the biosimilar. Both its efficacy in various therapeutic indications and its safety profile in diverse risk populations may be different from that of the innovator. Hence, compared to a chemical generic there is a bigger need for strict post-marketing product vigilance (including accurate identification of suspect product), and additional post-approval studies in the case of biosimilar products.
Additional risk management measures include following naming conventions to ensure traceability, having a product-specific risk management plan to address risks which may be different from those of the reference product, careful medical evaluation of all immunogenicity reports within the ‘risk window’, a product label with efficacy and safety information related to both reference and biosimilar product identified by source, and close post-approval monitoring of safety,
Pharmacovigilance and risk management for biosimilars presents a number of unique and signiﬁcant challenges. Routine PV processes may need to be adapted to address these issues. To learn more about these challenges and the possible solutions in safety monitoring and risk management read this whitepaper.