- 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
Kelly S Colletti
Senior Research Scientist
Laboratory Sciences, Charles River
6995 Longley Lane, Reno
NV 89511, USA
Tel: +1 775 682 2145
About the author
Kelly Colletti obtained her PhD in Cellular and Molecular Biology at the University of Nevada, Reno in 2005. She is a trained herpes virologist that studied the molecular mechanisms of Cytomegalovirus and Karposi’s Sarcoma Associated Herpes Virus DNA replication. While pursuing her doctoral degree, she learned a diverse set of skills including protein expression and purification, antibody generation, enzymatic assay development, cell culture, molecular biology and protein chemistry. She also obtained an MBA during this time and has a keen business sense. Her postdoctoral fellowship was also in virology developing a reverse genetics model for the Sin Nobre Hantavirus. Kelly joined Charles River in early 2009 and has since become the Program Director of Bioanalytical Sciences for preclinical and clinical services. She is also cross trained in immunotoxicology and has experience running studies in Non-Human Primates with immunophenotyping, TDAR, NK cell activity, and biomarker endpoints. Since joining CRL, Kelly has participated in over 15 biosimilar programs validating bioanalytical and immunogenicity assays to support preclinical and clinical studies. As an industry leader in this field, she has also authored several publications on the subject of biosimilars.
Key factors that influence biosimilar in vitro and in vivo nonclinical testing strategies
Over the years there have been varying opinions from regulatory authorities, industry and the scientific community, on whether nonclinical animal studies are required for demonstrating biosimilarity to an approved reference product. Key stakeholders, including industry and healthcare professionals, are seeking a standardized approach for the nonclinical in vitro and in vivo studies required to support a biosimilar program. However, as the scientific community gains more knowledge and experience in the development of biosimilars, it has become increasingly clear that a ‘one size fits all’ approach is not appropriate in the development of biosimilar products. Each class of biological product poses different scientific challenges and inherent risks based on the unique characteristics of each molecule, including the molecular structure and mechanism of action. This Chapter will review the current regulatory landscape with respect to the requirement for nonclinical studies (e.g., pharmacology, PK and toxicology), as well as the design and utility of animal studies. The strategy employed for in vitro and in vivo nonclinical testing applied in a biosimilar program can have a significant impact on the overall success and cost of the program. The business of biosimilar production and approval is a delicate balance between demonstrating similarity to an approved reference product using state-of-the-art methods while reducing R&D costs in order to deliver biologic medicines that elicit price competition in the marketplace.
Europe is recognized as leading the world in the acceptance of biosimilars in the marketplace. The European Medicines Agency (EMA) has issued various regulatory guidelines and has issued a number of positive opinions for biosimilar products in the past 10 years. To date, there are 19 marketing authorizations issued by the European Commision, including one somatropin, one insulin, five erythropoietins, eight filgrastims, two monoclonal antibodies (infliximab), and two follitropin alfa[1,2]. The first overarching guideline (Guideline on Similar Biological Medicinal Products) was established in 2005 and, subsequently, the first guideline for the scientific approaches for both in vitro and in vivo nonclinical studies was effective in 2006 (Guideline on similar biological medicinal products containing biotechnology-derived proteins as active substance: non-clinical and clinical issues) .