Seminar 4.2 - Diary by William Chin
Freiburg, March 8, 2014 - The major emphasis for EUCRAF’s Seminar 4.2 was on the non-clinical and clinical development of biopharmaceuticals. This was a continuation from Seminar 4.1 where the topics presented here specifically addressed the Module 4 and 5 requirements in the CTD. This seminar was led by Dr. Ronald Grobe-Einsler (formerly Bayer) and attended by a total of 29 participants.
The panel of speakers included Dr. Bernd Müller-Beckmann (formerly Roche Penzberg), Dr. Jennifer Sims (formerly Novartis, Integrated Biologix), Dr. Simon Day (Clinical Trials Consulting & Training Ltd), Dr. Paul Chamberlain (NDA Advisory Board, bioLOGICA Consulting), Dr. Alex Veldman (CSL Behring), Dr. Thomas Kirchlechner (Sandoz Biopharmaceuticals Development) and Dr. Gabriele Schäffner-Dallmann (EUCRAF). Unlike generic drugs where principally no preclinical testing is required, biosimilars demand extensive in vitro characterization. Particularly, the comparability exercise regarding physico-chemical characterization in comparison to the reference product has to be performed. Abbreviated clinical program is necessary to demonstrate the absence of clinically meaningful differences between the biosimilar and reference product. Traditional animal safety assessments will have limited value in determination of biosimilarity if the relevance of test species is not first established. A review of the Tegenero case was presented by Dr. Jennifer Sims, reminded us of how a drug candidate that was confirmed as safe and efficacious in preclinical studies, had a disastrous outcome in six human volunteers who faced life-threatening conditions. Immunogenicity in animals is not always predictive for humans. However, development of a suitable preclinical animal model supplemented with in vitro and ex vivo human assays as well as the use of appropriate biomarker coupled with risk mitigation approaches, could ensure the safety of healthy volunteers and patients in clinical trials. Dr. Ronald Grobe-Einsler highlighted the role of validated biomarkers and surrogate endpoints to support drug registration. A discriminative biomarker is needed to pre-screen patient populations or to predict the course of disease during drug development programs. Dr. Simon Day spoke about the need for a comprehensive understanding of the mode of action of “high-risk” mAbs and the importance of population selection and sequential inclusion of subjects in Phase 1 trial, dose selection and its titration, as well as risk assessment and mitigation plans. A pharmacovigilance system is to establish and maintain a favorable benefit-risk profile in patients. Dr. Paul Chamberlain gave a detailed presentation on the biology of immunogenicity and how it had become a subject of concern in the approval of biopharmaceuticals by regulators. Hence, the primary purpose of applying a risk-based approach to immunogenicity is to strengthen the awareness of the risks and minimizing unfavorable outcomes. Dr. Alex Veldman spoke passionately about his clinical experience with an orphan drug for the treatment of Molybdenum Cofactor Deficiency Type A, an ultra-rare, genetic metabolic disorder that causes irreversible neurologic damage in newborns. It’s a classic tale of bench to bedside of how basic preclinical investigation in a laboratory resulted in a new therapy for patients that progressed to drug registration with major global regulatory bodies around the world. In conclusion, this seminar provided lots of important take home messages pertaining to the development and approval of biosimilars. In addition, it was an excellent opportunity to network with fellow lectures and other participants as well. Seminar 5 on the development of medicinal product for children is scheduled in May 8, 2014 and I am looking forward to this exchange of ideas and knowledge.
William Chin is currently undertaking Master’s in Regulatory Affairs for Biopharmaceuticals at EUCRAF and previously obtained a Ph.D. in Biomedical Science from the Department of Pharmacy, National University of Singapore.