Amgen employs a stringent development process that is customized for each biosimilar. To begin, it is imperative that we understand the structure and function of the reference product. To do so, we review the literature on both the disease and the reference product.
Then we acquire the reference product and use sophisticated analytical tests to determine its CQAs, which:7
Then we identify the desired attribute profile of the reference product, subsequently requiring the development of manufacturing parameters that result in a biosimilar product. Scientists typically evaluate over 100 attributes of the biosimilar in comparison to the reference product,, determining which are most important for producing a biosimilar that meets regulatory standards for high quality. Only the amino acid sequence of the reference product is known, so it is impossible to exactly replicate the manufacturing process. The attributes of the biosimilar medicine are highly unlikely to ever be identical to those of the reference product. The manufacturing of biologics is complex as the required production systems (eg, cell lines) are highly sensitive to the manufacturing process. Therefore, differences between the originator biologic and biosimilar are expected, and may be acceptable, as long as they can be demonstrated not to produce any clinically meaningful differences in the biosimilar compared with the reference product.2,8,9
Amgen has the deep scientific capabilities needed to create and select a promising clone from literally thousands of cells. The optimal clone produces the antibody that matches the biological function of the reference product as closely as possible, promoting the development of a biosimilar that has no clinically meaningful differences from the reference product.2,7
Once the clone is chosen, we custom design a process to effectively produce the biosimilar with specific quality attributes so that the biosimilar is highly similar with no clinically meaningful differences to the reference product. This requires:8-10
References: 1. Boccia R, Jacobs I, Popovian R, de Lima Lopes G Jr. Can biosimilars help achieve the goals of US health care reform? Cancer Manag Res. 2017;9:197-205. 2. US Food and Drug Administration. Guidance for industry: scientific considerations in demonstrating biosimilarity of a therapeutic protein product to a reference product. www.fda.gov/downloads/drugs/guidances/ucm291128.pdf. Accessed October 29, 2019. 3. Mellstedt H, Niederwieser D, Ludwig H. The challenge of biosimilars. Ann Oncol. 2008;19:411-419. 4. US Food and Drug Administration. Guidance for industry: quality considerations in demonstrating biosimilarity of a therapeutic protein product to a reference product. www.fda.gov/downloads/drugs/guidances/ucm291134.pdf. Accessed October 29, 2019. 5. US Federal Trade Commission. Emerging health care issues: follow-on biologic drug competition: a federal trade commission report. www.ftc.gov/reports/emerging-health-care-issues-follow-biologic-drug-competition-federal-trade-commission-report. Accessed October 29, 2019. 6. EuropaBio. Guide to Biological Medicines: A Focus on Biosimilar Medicines. 2011. 7. Vulto AG, Jaquez OA. The process defines the product: what really matters in biosimilar design and production? Rheumatology. 2017;56:iv14-iv29. 8. Blauvelt A, Cohen AD, Puig L, Vender R, van der Walt J, Wu JJ. Biosimilars for psoriasis: preclinical analytical assessment to determine similarity. Br J Dermatol. 2016;174:282-286. 9. Desanvincente-Celis Z, Gomez-Lopez A, Anaya JM. Similar biotherapeutic products: overview and reflections. Immunotherapy. 2012;4:1841-1857. 10. Conner J, Wuchterl D, Lopez M, et al. The biomanufacturing of biotechnology products. In: Shimasaki C, ed. Biotechnology Entrepreneurship: Starting, Managing, and Leading Biotech Companies. Waltham, MA: Academic Press; 2014:351-385. 11. Dranitsaris G, Amir E, Dorward K. Biosimilars of biological drug therapies. Drugs. 2011;71:1527-1536. 12. Ramanan S, Grampp G. Drift, evolution, and divergence in biologics and biosimilars manufacturing. BioDrugs. 2014;28:363-372.