Abstract:
In principle, biosimilars could mitigate the problem of the rising cost of biological medicines. However, the current stringent and non-harmonized regulatory practices hinder competition and contribute to the high price level of biosimilars. The quality, safety, and efficacy of biosimilars developed, according to the current guidelines of ‘stringent’ regulatory agencies have proven to be excellent. Analytical and in vitro functional testing combined with clinical pharmacokinetic and pharmacodynamic studies provide the essential data to prove the similarity of candidate biosimilars to their reference products. The standard in vivo non-clinical toxicological studies are useless, and the value of ‘confirmatory’ controlled efficacy (and safety) trials have been questioned by several independent retrospective studies of current biosimilars, including monoclonal antibodies and fusion proteins. Thus, the development of biosimilars could be streamlined to lower costs without increasing risks to efficacy or safety of products. The UK regulatory agency, Medicines and Healthcare products Regulatory Agency (MHRA), and World Health Organization (WHO) have recently revised their biosimilar guidelines to allow the development of biosimilars without ‘confirmatory’ clinical efficacy studies when the biosimilar candidate can be thoroughly characterized and shown to be structurally and functionally similar to the reference product that has no unpredictable serious adverse effects. The European Medicines Agency (EMA) is already exploring possibilities to revise its guidance accordingly. Unfortunately, the US Food and Drug Administration (FDA) is still hesitating. The US guidance should be revised to remove the interchangeability studies and reduce the controlled efficacy trials. Otherwise, the global biosimilar market will not be able to provide better access to biological medicines.