Abstract
Regulatory approval of biosimilar products requires demonstration of analytical similarity of functional and structural attributes between the proposed biosimilar product and on-market reference product. The statistical framework for how to evaluate the analytical similarity data has recently been published and a U.S. regulatory guidance is expected soon. This paper illustrates the challenges and issues encountered by Hospira (a Pfizer company) in implementing this newly described statistical framework to support the analytical similarity assessments for biosimilar products. A simulation approach using multilevel (hierarchical) linear regression is also proposed to statistically derive shelf-life specification limits. The approach may be applicable when there is larger volume of data that can be generated as part of the analytical similarity assessment. The performance of the simulation approach is compared when there is a limited vs. sufficiently large sample size and when the quality attribute of interest has a low vs. high analytical variability. The proposed simulation approach to calculate shelf-life specification limits is also benchmarked against a commonly utilized approach in industry based on a fixed effect Analysis of Covariance (ANCOVA) model.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
FDA approves first biosimilar product Zarxio. March 6, 2015. Available at (http://www.fda.gov/newsevents/newsroom/pressannouncements/ucm436648.htm)
Scientific Considerations in Demonstrating Biosimilarity to a Reference Product: Guidance for Industry. April, 2015. Available at (http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM291128.pdf)
Tsong, Y., Shen, M., Dong, C. (2015), “Development of Statistical Approaches for Analytical Biosimilarity Evaluation”. Presentation at DIA Statistics Forum. April 2015. North Bethesda, MD
Burdick, R. K. and Ramírez, J. G. (2015) “Statistical Issues in Biosimilar Analytical Assessment: Perspectives on FDA ODAC Analysis, Presentation at DIA Conference, Washington, D. C., April.
Zhang, L. and Wu, S. (2015). “How to Set Biosimilarity Bounds in Biosimilar Developments”, Presentation at Joint Graybill and ICSA Annual Conference, Fort Collins, CO, June.
Chow, S.C. (2014). “On Assessment of Analytical Similarity in Biosimilar Studies”. Drug Des 3: 119. doi:10.4172/2169-0138.1000e124
Westlake, W. J. (1981). “Response to T. B. L. Kirkwood: Bioequivalence testing--a need to rethink. “Biometrics 37:589-594.
Schuirmann, D. J. (1987). “A comparison of the two one-sided tests procedure and the power approach for assessing the equivalence of average bioavailability.” J Pharmacokinet Biopharm 15(6): 657-680.
Q6A Specifications: Test Procedures and Acceptance Criteria for New Drug Substances and New Drug Products: Chemical Substances (2000). Available at http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/ucm134966.htm
Q6B Specifications: Test Procedures and Acceptance Criteria for Biotechnological / Biological Products (1999). Available at http://www.fda.gov/ucm/groups/fdagov-public/@fdagov-drugs-gen/documents/document/ucm073488.pdf
Q1A(R2) Stability Testing of New Drug Substances and Products (2003). Available at http://www.fda.gov/ucm/groups/fdagov-public/@fdagov-drugs-gen/documents/document/ucm073369.pdf
Q1E Evaluation of Stability Data (2004). Available at http://www.fda.gov/ucm/groups/fdagov-public/@fdagov-drugs-gen/documents/document/ucm073380.pdf
Allen, P. V., Dukes, G. R. and Gerger, M. E. (1991). “Determination of release limits: a general methodology.” Pharm Res 8(9): 1210-1213.
Murphy, J. R. and Hofer J. D. (2002). “Establishing Shelf Life, Expiry Limits, and Release Limits.” Drug Information Journal 36(4): 769-781.
Schofield, T., Apostol, I., Koeller, G., Powers, S., Stawicki, M. and Wolfe, R. A. (2008). “A Rational Approach for Setting and Maintaining Specifications for Biological and Biotechnology-Derived Products - Part 2.” Biopharm International 21(7).
Dong, X., Tsong, Y. and Shen, M. (2014). “Statistical Considerations in Setting Product Specifications.” Journal of Biopharmaceutical Statistics 25(2): 280-294.
Gelman, A. and Hill, J. (2007). Data analysis using regression and multilevel/hierarchical models. New York, NY, Cambridge University Press.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2016 Springer International Publishing Switzerland
About this paper
Cite this paper
Montes, R., Bernat, B., Srebalus-Barnes, C. (2016). Statistical Applications for Biosimilar Product Development. In: Lin, J., Wang, B., Hu, X., Chen, K., Liu, R. (eds) Statistical Applications from Clinical Trials and Personalized Medicine to Finance and Business Analytics. ICSA Book Series in Statistics. Springer, Cham. https://doi.org/10.1007/978-3-319-42568-9_20
Download citation
DOI: https://doi.org/10.1007/978-3-319-42568-9_20
Published:
Publisher Name: Springer, Cham
Print ISBN: 978-3-319-42567-2
Online ISBN: 978-3-319-42568-9
eBook Packages: Mathematics and StatisticsMathematics and Statistics (R0)