Biologics: EMA Concept Paper on the Revision of the Guideline on Similar Biological Medicinal Products Containing Biotechnology-derived Proteins as Active Substance: Non-clinical and Clinical Issues

The Biotechnology Industry Organization (BIO) thanks the European Medicines Agency (EMA) for the opportunity to submit comments on “Concept paper on the revision of the guideline on similar biological medicinal products containing biotechnology-derived proteins as active substance: non-clinical and clinical issues.”

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.

BIO notes that the concept paper does not address immunogenicity in the context of risk management plans. In some situations, neutralizing antibodies can result in important clinical consequences for patients, and a sponsor may need to provide ongoing antibody evaluation support services to support the risk management plan; this would also permit a physician to confirm the cause of an unwanted drug reaction (whether immunogenicity or loss of efficacy) and, hence, make a better informed decision on therapy.

BIO suggests consideration for more information on extrapolation to sensitive patient populations. It is suggested that the criteria outlined in the World Health Organization (WHO) guideline may be a useful starting place. In particular, it would be helpful to have guidance with an emphasis on studying biosimilarity in these specific patient populations with regards to clinical effect. BIO suggests the criteria for extrapolation should discuss when a similar safety or immunogenicity profile may be inferred from the less sensitive population when these situations might be addressed in a risk management plan, or when comparative studies are required prior to receiving marketing authorization for such indications.

Specific, detailed comments are included below. We would be pleased to provide further input or clarification of our comments, as needed.