Biosimilars: BIO Comments to EMA on their Biosimilars Guideline on Non-clinical/Clinical Considerations

The Biotechnology Industry Organization (BIO) thanks the European Medicines Agency (EMA) for the opportunity to submit comments on the revised “Guideline on similar biological medicinal products containing biotechnology-derived proteins as active substance: non-clinical and clinical issues (EMEA/CHMP/BMWP/42832/2005 Rev. 1).” BIO commends EMA on the update of this Draft Guideline, which provides an important international precedent for the development and regulation of biosimilar biological medicinal products.

BIO represents more than 1,100 biotechnology companies, academic institutions, state biotechnology centers and related organizations across the United States and in more than 30 other nations. BIO members are involved in the research and development of innovative healthcare, agricultural, industrial and environmental biotechnology products, thereby expanding the boundaries of science to benefit humanity by providing better healthcare, enhanced agriculture, and a cleaner and safer environment.

In general, BIO agrees that a stepwise approach is desirable in biosimilar development, beginning with physicochemical similarity before commencing non-clinical and final clinical development.

BIO also agrees that ‘the nature and complexity of the reference product has an impact on the extent of the (non-) clinical studies to confirm biosimilarity,’ however, we strongly believe that it is ultimately the degree to which the reference product can be elucidated, in terms of both its physiochemical properties at its molecular level and its mechanism of action (MoA), that will have an influence on the amount of work required to confirm biosimilarity.

While BIO considers extrapolation between indications an important consideration underlying the biosimilar framework, BIO strongly believes that it is important to ensure that each extrapolated indication is fully justified. BIO believes that it is clear that additional evidence will usually be required, although it may differ depending on clinical experience, available literature data, MoA of the active substance of the reference product in each indication, and the receptors involved. Such additional evidence and justification are necessary to demonstrate separately the safety and efficacy of each of the extrapolated indications. This general principle is set out in the Annex to Directive 2001/83, as amended, and we ask that the competent authorities follow it and carefully review the justifications provided by the biosimilar applicants.

BIO appreciates this opportunity to comment on the revised “Guideline on similar biological medicinal products containing biotechnology-derived proteins as active substance: non-clinical and clinical issues (EMEA/CHMP/BMWP/42832/ 2005 Rev. 1).” We would be pleased to provide further input or clarification of our specific, detailed comments, which follow in Section 2, as needed.