BioRationality: No More Clinical Efficacy Testing for Biosimilars, Going From Biosimilars to Biogenerics

The limited entry of biosimilars and their still unaffordable cost1 due to the cost of development, which ranges from $100 to $300 million each.2 Most of this cost is attributed to clinical efficacy studies (CES)3 heavily pushed by big pharma companies.4 Europe took the lead, but the FDA continued to require CES, except for a few cytokines with pharmacodynamic properties, leaving the largest category of monoclonal antibodies requiring extensive clinical testing. The irony of these testing requirements is that these studies can never fail, but that was not fully appreciated, being the first of their kind of studies ever required by the regulatory agencies.5

After decades of filing citizen petitions,6 publishing research papers,7 and meeting with FDA decision makers, convincing US senators to introduce bills to amend the Biologics Price Competition and Innovation Act,8 things began to move. First came the removal of animal toxicology testing for biosimilars, which I had strongly objected9 to, followed by an administrative change to remove interchangeability as I had suggested to the FDA, effectively,10 but the major requirement of CES had remained intact for monoclonal antibodies. Finally, I received a letter on August 25, 2025, which indicated that the agency may finally officially waive CES for biosimilars.11 This position of the FDA will consolidate the regulatory framework for all regulated agencies, allowing for faster entry of biosimilars from smaller companies, which will lead to a significant reduction in their cost to patients.

Now, a lot will change about how the biosimilars are developed, marketed, and made available to patients. First, I see a fast retraction of big pharma staying in the biosimilar market—this is the same history that took place when generics came. Second, the market value of companies that are planning to invest heavily in CES will go down, and third, the associations that keep repeating the theme of using more biosimilars to save more will disappear.

This is the time for smaller companies to bring out their plans since the cost of a new biosimilar approval should not exceed $10 million if a US contract development and manufacturing organization is developing and supplying the biosimilar; many companies can shrink it to no more than a 505(b)(2) filing. No longer is there a need to discuss how to promote biosimilars; they will find their own way just like the generics have done. I began by writing the first book that identified them as biogenerics, then it went to biosimilars, and now it is returning to biogenerics.

References

1. Rathore AS, Gardner PJ, Chhabra H, Raman R. Global outlook on affordability of biotherapeutic drugs. Ann N Y Acad Sci. 2024;1537(1):168-178. doi:10.1111/nyas.15171

2. Fontanillo M, Körs B, Monnard A. Three imperatives for R&D in biosimilars. McKinsey & Company. Published August 19, 2022. Accessed September 16, 2025. https://www.mckinsey.com/industries/life-sciences/our-insights/three-imperatives-for-r-and-d-in-biosimilars

3. Niazi SK. Scientific justification and policy recommendations to the US Food and Drug Administration for waiving comparative efficacy studies. Pharmaceuticals. 2025;18(6):779. doi:10.3390/ph18060779

4. Brennan Z. Amgen's Leah Christl makes the case to keep the interchangeability designation for biosimilars. Endpoints News. Published September 12, 2023. Accessed September 16, 2025. https://endpoints.news/amgens-leah-christl-makes-the-case-to-keep-the-interchangeability-designation-for-biosimilars

5. Niazi SK. Biosimilars adoption: recognizing and removing the roadblocks. Clinicoecon Outcomes Res. 2023;15:281-294. doi:10.2147/CEOR.S404175

6. Regulations.gov. Niazi and FDA. Published 2025. Accessed September 16, 2025. https://www.regulations.gov/search?filter=niazi%20fda

7. Niazi SK. A timely recommendation to the European Medicines Agency and the FDA on rationalizing comparative clinical efficacy testing of biosimilars. Discov Med. 2024;1:87. doi:10.1007/s44337-024-00107-6

8. Sen. Lee introduces biosimilar red tape elimination act. Senator Mike Lee’s 8. website. Published November 17, 2022. Accessed September 16, 2025. https://www.lee.senate.gov/2022/11/sen-lee-introduces-biosimilar-red-tape-elimination-act

9. Niazi SK. End animal testing for biosimilar approval. Science. 2022;377(6602):162-163. doi:10.1126/science.add4664

10. Niazi SK. No two classes of biosimilars: urgent advice to the US Congress and the FDA. J Clin Pharm Ther. 2022;47(9):1352-1361. doi:10.1111/jcpt.13743

11. Professor Sarfaraz K. Niazi secures first-ever FDA acceptance to waive clinical efficacy studies for monoclonal antibody biosimilars. News release. Yahoo Finance. Published September 1, 2022. Accessed September 16, 2025. https://finance.yahoo.com/news/professor-sarfaraz-k-niazi-secures-142300145.html