- Chapter 1: Current regulatory landscape for biosimilars approval
- Chapter 2: Overview of biosimilars development
- Chapter 3: Case Studies: EU Regulatory Guidelines and how to interpret them
- Chapter 4: Analytical Comparability (chemistry, manufacturing and controls related product attributes)
- Chapter 5: Key factors that influence biosimilar in vitro and in vivo nonclinical testing strategies
- Chapter 6: Immunogenicity assessment for biosimilars: assay development, validation and interpretation
- Chapter 7: Case studies: challenges of developing and validating PK and immunogenicity assays to support pre-clinical and clinical comparability studies for biosimilars
- Chapter 8: Biosimilar monoclonal antibodies
Laboratory for Therapeutic & Diagnostic Antibodies
Department of Pharmaceutical & Pharmacological Sciences
KU Leuven, Campus GHB, ON2,
PB 820, 3000 Leuven, Belgium
Tel. +32 16 323431
About the author
Professor Paul J Declerck, obtained his Ph.D. in Pharmaceutical Sciences from the University of Leuven (Leuven, Belgium) in 1984. After post-doctoral training in the Laboratory of Biochemical Cytology at the Rockefeller University (New York, USA) with Professor C de Duve, he joined the Center for Molecular and Vascular Biology with Prof D Collen, at the University of Leuven, in 1986. In 1991, he was appointed Professor of Pharmaceutical Biotechnology at the Faculty of Pharmaceutical Sciences, and then became full Professor in 1997. He is currently Research Director of the Laboratory for Therapeutic and Diagnostic Antibodies at the Department of Pharmaceutical and Pharmacological Sciences (University of Leuven). His research is focused on structure–function relationships of (recombinant) proteins and on the development of monoclonal antibodies for research, diagnostic and therapeutic purposes. He has expertise in the area of recombinant proteins, monoclonal antibody technology, biotechnology, drug development, structure–function relationship in proteins and biosimilars.
Prof. Declerck has given numerous invited lectures at international meetings and has authored over 220 scientific papers in peer-reviewed journals.
He is President of the Commission of Medicines for human use of the Belgian Federal Agency for Medicines and Health Products, Dean of the faculty of Pharmaceutical Sciences of the University of Leuven, President of the International Society for Fibrinolysis and Proteolysis, and member of various international scientific advisory boards.
According to PubMed, the term ‘biosimilar’ has existed for 10 years in scientific literature, with the first biosimilar having been introduced onto the European market in 2006. Early biosimilars concerned relatively small proteins such as human growth hormone, epoetin and filgrastim. In 2013, the first biosimilar monoclonal antibody (infliximab) was approved. It is beyond any doubt that the emergence of biosimilars has an important impact on biopharmaceutical companies involved in the production of biotechnological medicines. This is also illustrated by the fact that biosimilars from blockbuster drugs are currently also being developed by competing ‘originator’ companies.
Bringing copies of off-patent biotechnological drugs to the market has required the development of particular guidelines by regulatory authorities. Chapters 1–3 in this e-book cover the various aspects of these issues, and the consequences for biosimilar development and the analytical requirements. The concept of biosimilar development is based on a very detailed, thorough analytical comparison between the biosimilar and its reference product. General aspects that need to be taken into account and particular concerns (e.g., analysis of glycosylation patterns) regarding physicochemical characterization are discussed in Chapter 4. Once sufficient bioanalytical similarity has been demonstrated, it is acceptable to reduce the extent of nonclinical tests as discussed in Chapter 5. Immunogenicity is one of the major concerns and requires well-developed and characterized assays for detection of an antibody response towards the drug. Chapters 6 and 7 discuss important aspects in the design and validation of these assays, and the possible impact of external factors. Finally, Chapter 8 is devoted in particular to scientific and regulatory issues for the safe approval of biosimilar monoclonal antibodies.
It is clear that the field of biosimilars has evolved considerably and is likely to be subject to significant expansion in the future. Scientific progress in the area of analytical techniques is expected to allow an even more detailed comparative analysis of biosimilars against reference products. One of the key challenges will be to judge in a reliable and predictive manner which differences may, or may not, have an impact on the safety or efficacy of the biosimilar. This may subsequently result in less pre-approval clinical studies for granting market authorization. Finally, the future will have to tell whether, or not, the introduction of biosimilars really contributes towards a sustainable healthcare budget.