Development of biosimilars--pharmacokinetic and pharmacodynamic considerations.

The European Medicines Agency (EMEA) leads in providing regulatory guidelines to this emerging industry. While biosimilars are not yet available in the United States, as the legal and regulatory pathway is being developed there, biosimilars and other such products are marketed in other regions of the world. We reviewed the European assessment reports of biosimilars to gain insights into the current practices pertaining to the pharmacokinetic (PK) and pharmacodynamic (PD) similarity evaluations because we believe that they might help to shape the future global regulatory landscape. This paper illustrates the molecular complexity of therapeutic proteins, challenges associated with PK and PD evaluations, limitations of similarity assessment using PK and PD endpoints, and design considerations for PK and PD studies. The scope of biotechnology-derived products will be limited to therapeutic protein products, including recombinant human proteins, fusion proteins, and monoclonal antibodies. The challenges to demonstrate similarity are complex and appear to be unique to each therapeutic agent; therefore, the requirements for regulatory approval will most likely continue to be handled at a product-specific level as stipulated in current EMEA guidelines.