An Overview of Current Regulatory Requirements for Approval of Biosimilar Insulins.

Insulin analog patent expiry is likely to mean that, increasingly, copies of original biopharmaceutical products will be submitted for authorization. Experience with biosimilars in other therapeutic areas suggests that careful regulation and caution are needed. Published guidelines of regulatory authorities around the world on approval of biosimilars and, where available, insulin biosimilars were reviewed. Information was sourced through Internet searching and cross-referencing guidelines. As of August 2014, general biosimilar and insulin-specific guidelines are available in 34 countries and two countries/regulatory domains, respectively. Many guidelines are clearly related to, or partly derived from, the general and insulin-specific European Medicines Agency (EMA) guidelines. Areas covered by these guidelines are fairly consistent, covering preclinical, pharmacokinetic (PK), and pharmacodynamic (PD) studies in humans and clinical areas; however, there are differences in emphasis. The EMA insulin-specific guidelines include detailed criteria on PK/PD studies, as do most other general biosimilar guidelines and, to a lesser extent, clinical studies. The U.S. Food and Drug Administration has general biosimilar guidelines, emphasizing consideration of the whole package of in vitro, biological, and human studies, rather than concentrating on any one aspect. In countries such as Mexico, guidelines are broad, leaving wide discretion to the regulatory authority. In conclusion, from a global perspective, this area of drug regulation is heterogeneous and evolving, and the authors call for an initiative aimed at harmonizing the requirements for biosimilar insulins.

The biosimilar insulin landscape: current developments.

Biosimilar insulins have the potential to increase access to treatment among patients with diabetes mellitus, reduce treatment costs, and expand market competition. The patents for several insulins are soon to expire, meaning there is room for copies of these products--or 'biosimilars'--to join the marketplace. It is vital that similar safety and efficacy to the innovator product is demonstrated for biosimilars. This presents many possible manufacturing and regulatory challenges. Complex manufacturing processes mean that even small differences between manufacturers can have a potential impact on the final product. Several companies are currently developing biosimilar insulins or are already producing these products in emerging markets with different regulatory requirements. For insulin biosimilars to be licensed in more established markets, manufacturers will need to meet the rigid criteria set out by agencies such as the European Medicines Agency and US Food and Drug Administration, and fulfill several pre-clinical, clinical, and pharmacovigilance surveillance criteria. As a result of differing regulatory requirements, there are possible gaps in the publically available clinical data to support the safety and efficacy of biosimilar insulins from around the world current as of July 2014. This review summarizes the current biosimilar insulin landscape.