Despite already having been in the U.S. market for many years,2 biosimilars still face skepticism and confusion from patients, prescribers, and payers around how they are made, what the difference is between biosimilars and generics, and what the biosimilars approval pathway looks like.3 The below FAQs address these topics and a few others to offer an introductory understanding of biosimilars and their development process.
A biosimilar is a biologic, or medication that comes from a living source, that is highly similar to, and has no clinically meaningful differences from, the biologic that is already approved by the FDA (known as the originator biologic).1
Biosimilars and generic drugs are not the same. Biosimilars have a different molecular size and structure from generics. Additionally, generics are copies of synthetic drugs (created from chemicals), while biosimilars are modeled after biologics, which are derived from a living source.
The manufacturing process for generic drugs will result in an active ingredient that is the same within each manufactured lot and between lots, whereas biosimilars will have inherent variation (i.e., small changes to the protein molecule) within each lot and between lots as a natural part of their manufacturing process. As a result, the research and development of biosimilar drugs is much more complex and costly than that of generics.4
The Biologics Price Competition and Innovation Act (BPCIA), signed into law in 2010 as part of the Affordable Care Act, established an abbreviated approval pathway for biosimilars in the U.S.5 The goal of a biosimilar development program is to demonstrate biosimilarity between the proposed biosimilar and its originator biologic, not to independently establish the safety and effectiveness of the proposed biosimilar. This generally means that biosimilar manufacturers do not need to conduct as many expensive and lengthy clinical trials.5
Biologics are the fastest-growing class of medications in the United States and account for a substantial and growing portion of health care costs.6 Because of that, the BPCIA created an abbreviated approval pathway to help provide patients with greater access to safe and effective biological products. This pathway helps reduce the time and cost of development without compromising safety and effectiveness.5
Biosimilar manufacturers will typically include the following data in an application:
Because biologics contain active substances derived from living cells or organisms, the development of a biosimilar is much more complex than the process for developing a small-molecule generic drug.
A biosimilar requires the creation of a new manufacturing process and a custom cell line, since the originator biologic’s manufacturing process is proprietary and not publicly available.7 Due to the complex nature and production methods of biologics, relatively minor changes in manufacturing processes may significantly affect product quality, safety, and efficacy.8
Based on the provisions in the BPCIA, the FDA recommends a step-by-step biosimilar development approach to identify any potential clinically meaningful differences between biosimilars and their originator biologics.9
Comparative clinical testing as part of the biosimilar development program is needed to demonstrate that no clinically meaningful differences exist in terms of safety and efficacy between a biosimilar and its originator biologic.
The clinical program generally includes a comparative pharmacokinetics study (with a pharmacodynamics comparison where suitable biomarkers exist), which is commonly conducted in healthy volunteers. This is typically followed by a comparative clinical study that is designed to assess comparative efficacy, safety, and immunogenicity in at least one relevant and sensitive patient population.
The aim of the comparative clinical efficacy studies is not to re-establish safety and efficacy, as this has already been established independently for the originator biologic. Rather, the aim is to confirm that there are no clinically meaningful differences between the potential biosimilar and the originator biologic.10
To learn more about the promise of biosimilars, the impact they can create, and our work in this space, visit the following pages:
1. US Food and Drug Administration. What is a biosimilar? https://www.fda.gov/media/108905/download.
2. Biosimilars in the United States 2023-2027. IQVIA. https://www.iqvia.com/insights/the-iqvia-institute/reports/biosimilars-in-the-united-states-2023-2027. Published January 31, 2023.
3. Cohen H, McCabe D. The importance of countering biosimilar disparagement and misinformation. BioDrugs 2020;34(4):407-414.
4. Decreasing drug costs through generics and Biosimilars. National Conference of State Legislatures. https://www.ncsl.org/health/decreasing-drug-costs-through-generics-and-biosimilars. Published January 21, 2022.
5. Biologics Price Competition and Innovation Act, HR 3590, 111th Cong (2009). Pub L No. 111-148. https://www.fda.gov/media/78946/download.
6. Center for Drug Evaluation and Research. Biosimilars review and approval. U.S. Food and Drug Administration. https://www.fda.gov/drugs/biosimilars/review-and-approval.
7. Dolinar RO. Biosimilars are not generics. Healio. March 17, 2015. Accessed July 12, 2022. https://www.healio.com/news/endocrinology/20150317/j500_1303_01_news_print_4.
8. Mellstedt H, Niederwieser D, Ludwig H. The challenge of biosimilars. Ann Oncol. 2008;19(3):411-419.
9. U.S. Food and Drug Administration. Scientific Considerations in Demonstrating Biosimilarity to a Reference Product. April, 2015. https://www.fda.gov/media/82647/download.
10. Stebbing J, Mainwaring P, Curigliano G, et al. Understanding the role of comparative clinical studies in the development of oncology biosimilars. J Clin Oncol. 2020;38(10):1070-1080.