The next generation
Our process is what defines us
At Amgen, we excel at the highly specialized, iterative process of developing monoclonal antibodies in vitro, scaling up the optimal cell line, time and again, in large-scale bioreactors, and checking and rechecking for batch-to-batch consistency.4,5
Engineering a biosimilar
On the basis of a reference biologic’s critical quality attributes (CQAs), a biosimilar is engineered to be highly similar in terms of host cell proteins, product attributes, variants, process impurities, and stability profile.
Characterization and comparative studies
High similarity in analytical and pharmacokinetic/pharmacodynamic (PK/PD) data between the reference biologic and the biosimilar indicates a lower risk of clinical differences.
Quality standards in manufacturing
Rigorous quality standards throughout the manufacturing process and extensive risk assessments ensure product safety and efficacy.
Medicines born of living cells
Our biologic medicines are manufactured using living cells engineered to produce therapeutic proteins in large quantities. Those cells are very sensitive to conditions produced during their synthesis and handling, and a series of culturing and purification steps are required to produce a consistent, high-quality active ingredient.8
An extensive screening process is used, consisting of the following steps:
- Process line development
- Cell expansion
- Cell culture
- Purification (multiple steps)
- Virus inactivation/removal
- Packaging and storage
- Quality assurance and characterization
- Stability testing
The complexities of biosimilar manufacturing
All of the complexities of manufacturing biologics apply to biosimilar medicines as well. But biosimilar creation also has its own set of intricacies.
References: 1. Kozlowski S. US FDA perspectives on biosimilar biological products. Presented at: 2014 Biotechnology Technology Summit; June 13, 2014; Rockville, MD. www.ibbr.umd.edu/sites/default/files/public_page/Kozlowski%20-%20Biomanufacturing%20Summit.pdf. Accessed April 24, 2018. 2. US Food and Drug Administration. Quality Considerations in Demonstrating Biosimilarity of a Therapeutic Protein Product to a Reference Product: Guidance for Industry. www.fda.gov/downloads/drugs/guidances/ucm291134.pdf. Published April 2015. Accessed April 25, 2018. 3. US Food and Drug Administration. Scientific Considerations in Demonstrating Biosimilarity to a Reference Product: Guidance for Industry. www.fda.gov/downloads/drugs/guidances/ucm291128.pdf. Published April 2015. Accessed April 20, 2018. 4. Desanvicente-Celis Z, Gomez-Lopez A, Anaya J-M. Similar biotherapeutic products: overview and reflections. Immunother. 2012;4:1841-1857. 5. Ramanan S, Grampp G. Drift, evolution, and divergence in biologics and biosimilars manufacturing. BioDrugs. 2014;28:363-372. 6. Bee JS, Randolph TW, Carpenter JF, Bishop SM, Dimitrova MN. Effects of surfaces and leachables on the stability of biopharmaceuticals. J Pharma Sci. 2011;100:4158-4170. 7. 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. 8. Lybecker KM. The biologics revolution in the production of drugs. Fraser Institute. www.fraserinstitute.org/studies/biologics-revolution-in-the-production-of-drugs. Accessed April 25, 2018. 9. Dranitsaris G, Amir E, Dorward K. Biosimilars of biological drug therapies. Drugs. 2011;71:1527-1536. 10. Liu HF, Ma J, Winter C, Bayer R. Recovery and purification process development for monoclonal antibody production. mAbs. 2010;2:480-499. 11. Mellstedt H, Niederwieser D, Ludwig H. The challenge of biosimilars. Ann Oncol. 2008;19:411-419. 12. Roger SD. Biosimilars: how similar or dissimilar are they? Nephrology. 2006;11:341-346. 13. Hesse F, Wagner R. Developments and improvements in the manufacturing of human therapeutics with mammalian cell cultures. Trends Biotechnol. 2000;18:173-180.