ABSTRACT
The WHO informal consultation was held to promote the revision of WHO guidelines on evaluation of similar biotherapeutic products (SBPs) adopted by the Expert Committee on Biological Standardization (ECBS) in 2009. It was agreed in the past consultations that the evaluation principles in the guidelines are still valid, but a review was recommended to provide more clarity and case-by-case flexibility. The opportunity was therefore taken to review the experience and identify areas where the current guidance could be more permissive without compromising its basic principles, and where additional explanation could be provided regarding the possibility of reducing the amount of data needed for regulatory approval. The meeting participants applauded the leading role taken by the WHO in providing a much-needed streamlined approach for development and evaluation of SBPs which will provide efficient and cost-effective product development and increase patient access to treatments. It was recognized that the principles as currently described in the draft WHO guidelines are based on sound science and experience gained over the last fifteen years of biosimilar approvals. However, since these guidelines when finalised will constitute the global standard for biosimilar evaluation and assist national regulatory authorities in establishing revised guidance and regulatory practice in this complex area, it was felt that further revision and clarity on certain perspectives in specific areas was necessary to dispel uncertainties arising in the current revised version. This report describes the principles in the draft guidelines, including topics discussed and consensus reached.
Subject(s)
Biosimilar Pharmaceuticals , Humans , Referral and Consultation , World Health OrganizationABSTRACT
Although biosimilars approved in the European Union have proved to be safe and efficacious, their licensing requirements continue to be disputed by medical professionals. In particular, extrapolation to indications of the originator without one's own clinical data of the biosimilar is controversial. Conceptually, the development of biosimilars is derived from that of generics. However, due to their complexity and inherent variability, considerably more data are necessary for biosimilars to demonstrate comparability with the originator (the reference product) than for the usually low-molecular generics. Biosimilars increase competition and help contain healthcare, and they improve access for patients to valuable treatments with biologicals. However, biosimilar development is a laborious and lengthy process and requires major biotechnological know-how. The basis is comprehensive, structural, and functional characterization of the biosimilar and reference product as well as their comparison with suitable and sensitive methods. The clinical development programme is reduced and tailored to address remaining uncertainties and to confirm comparable clinical performance. Extrapolation of data to other indications of the reference product is the greatest cost advantage of biosimilar development, but must always be scientifically justified and, if necessary, substantiated by further data. The scientific principles underlying the comparability exercise for a biosimilar are the same as those applied to a change in the manufacturing process of an already licensed biological. In both cases, different versions of a biological substance are compared and the clinical relevance of observed differences is assessed. Competent authorities do have decades of experience in evaluating changes in the manufacturing process, which they can now apply to biosimilars. For approval of a biosimilar and extrapolation of data, the totality of the evidence from the complete comparability exercise is considered, as has been the case for the first biosimilar infliximab.