Principles of Analytical Similarity Assessment
Detailed evaluation of the similarity in structural and functional properties between a proposed biosimilar product and the reference product necessitates a carefully designed analytical study program. Although regulatory agencies, such as EMA and US FDA, have published guidance documents outlining the requirements for analytical similarity assessment, the implications are often not fully understood by biosimilar developers. This chapter discusses important considerations for all aspects of the design of the analytical similarity assessment, including the selection of the test materials; the product characteristics to be compared, and the associated analytical testing methods and plan; suitability of analytical procedures, in design and performance; processing and interpretation of analytical test data; and the methods for assessment of analytical study results. The design of comparative forced degradation studies, intended to compare the pattern and kinetics of product degradation, is also discussed. Differences in regulatory expectations between EU and USA are identified, together with their implications for the conception of a study program intended to support product approval in both jurisdictions.
KeywordsAnalytical similarity Analytical methods Biosimilar Quality attributes Forced degradation Tiering Criticality assessment Process shift Design of experiments Statistics
- CMC Biotech Working Group. A-Mab: a case study in bioprocess development (version 2.1). October 30, 2009.Google Scholar
- Dong X (Cassie). 2nd Statistical and Data Management Approaches for Biotechnology Drug Development; 2015 Sept 29–30; Rockville, MD, USA.Google Scholar
- EMA. CHMP/437/04 Rev 1: guideline on similar biological medicinal products. October 23, 2014a.Google Scholar
- EMA. EMA/CHMP/BWP/247713/2012: guideline on similar biological medicinal products containing biotechnology-derived proteins as active substance: quality issues (revision 1). May 22, 2014b.Google Scholar
- EMA. EMA/CHMP/138502/2017: reflection paper on statistical methodology for the comparative assessment of quality attributes in drug development (draft). March 23, 2017a.Google Scholar
- EMA. Herceptin European public assessment report - scientific discussion. [Online] [Cited: May 10, 2017b.] http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Scientific_Discussion/human/000278/WC500049816.pdf.
- EMA. Aranesp product information - all authorised presentations. [Online] [Cited: February 23, 2018.] http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_All_Authorised_presentations/human/000332/WC500026150.pdf.
- European Biopharmaceutical Enterprises (EBE). Concept paper: forced degradation studies for therapeutic proteins. March 24, 2015.Google Scholar
- European Parliament and Council. EU directive 2001/83/EC (As Amended). s.l. : EudraLex Vol. 1; Consolidated Version.Google Scholar
- European Parliament and Council. Directive 2004/27/EC. March 31, 2004.Google Scholar
- Eurostat. Eurostat: statistics explained. http://ec.europa.eu/eurostat/statistics-explained/index.php/Glossary:Observation_unit.
- Freitag AJ. The immunogenicity of protein aggregates: studies on a murine monoclonal antibody in wild-type mice. Ph.D. thesis, Faculty of Chemistry and Pharmacy, Ludwig-Maximilians-Universität München, Munich, Germany (2012)Google Scholar
- ICH. Q5C: stability testing of biotechnological/biological products. November 30, 1995.Google Scholar
- ICH. Q1D: bracketing and matrixing designs for stability testing of new drug substances and products. February 7, 2002.Google Scholar
- ICH. Q5E: comparability of biotechnological/biological products subject to changes in their manufacturing process. November 18, 2004.Google Scholar
- ICH. Q8(R2): pharmaceutical development. August 2009.Google Scholar
- Karow M. Applying risk ranking for similarity into the QTPP for antibody biosimilars. 2016 PDA biosimilars conference, Baltimore, MD, USA. 20–21 June 2016.Google Scholar
- Rhiel GS, Chaffin WW. An investigation of the large-sample/small-sample approach to the one-sample test for a mean (sigma unknown). J Stat Educ. 1996;4(3). https://doi.org/10.1080/10691898.1996.11910515
- Schmidt AS. Forced degradation studies for biopharmaceuticals. BioPharm Int. 2016;29(7):54–7.Google Scholar
- Stangler T. What to control? CQAs and CPPs. 2011 BWP workshop on setting specifications, London, UK. September 9, 2011.Google Scholar
- Tsong Y, Dong X, Shen M. Development of statistical methods for analytical similarity assessment. J Biopharm Stat. 2015 Sep 15. https://doi.org/10.1080/10543406.2015.1092038. [Epub ahead of print].
- U.S. FDA. Guidance for industry: immunogenicity assessment for therapeutic protein products. August 2014.Google Scholar
- U.S. FDA. Guidance for industry: scientific considerations in demonstrating biosimilarity to a reference product. April 2015a.Google Scholar
- U.S. FDA. Guidance for industry: quality considerations in demonstrating biosimilarity of a therapeutic protein product to a reference product. April 2015b.Google Scholar
- U.S. FDA. Guidance for industry: clinical pharmacology data to support a demonstration of biosimilarity to a reference product. December 2016.Google Scholar
- U.S. FDA. Guidance for industry (draft): statistical approaches to evaluate analytical similarity (withdrawn June-2018). September 2017.Google Scholar
- U.S. FDA. Aranesp (BLA 103951), SUPPL-5374: label. Drugs@FDA: FDA approved drug products. [Online] [Cited: February 23, 2018.] https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/103951s5374lbl.pdf.
- U.S. FDA CDER. Quality review BLA761042 - GP2015 (etanercept), Sandoz. 2016.Google Scholar
- Varchetta S, Gibelli N, Oliviero B, Nardini E, Gennari R, Gatti G, Silva LS, Villani L, Tagliabue E, Ménard S, Costa A, Fagnoni F. Elements related to heterogeneity of antibody-dependent cell cytotoxicity in patients under trastuzumab therapy for primary operable breast cancer overexpressing HER2. Cancer Res. 2007;67:11991–9.CrossRefGoogle Scholar
- Zhong X, Somers W. Recent advances in glycosylation modifications in the context of therapeutic glycoproteins. [book auth.] Dr. Hon-Chiu Leung. Integrative proteomics. London: InTech Open Access; 2012.Google Scholar