Biological drugs offer groundbreaking solutions for the treatment of cancer, autoimmune diseases, and chronic conditions. However, the high cost of these drugs poses a significant barrier that limits patient access. Biosimilar drugs are critical alternatives that demonstrate a high degree of similarity to reference biological products and have the potential to reduce costs. In this context, the new draft guidance published by the U.S. Food and Drug Administration (FDA) has the potential to fundamentally change biosimilar development processes and usher in a new era for clinical research centers.
FDA’s New Draft Guidance: A Revolution in Scientific Approach
With its draft guidance titled “Scientific Considerations in Demonstrating Biosimilarity to a Reference Product: Updated Recommendations for Assessing the Need for Comparative Efficacy Studies,” the FDA aims to significantly simplify the biosimilar licensing process [1]. This reform is based on a reassessment of the need for Comparative Efficacy Studies (CES, phase 3).
Previous regulations typically required comprehensive CES, which took 1 to 3 years and cost an average of $24 million, to prove biosimilarity. However, based on accumulated data and scientific experience, the FDA has determined that these studies generally have lower sensitivity compared to other analytical assessments.
The new guidance adopts a **“Streamlined Approach”** that recommends biosimilar developers rely on Comprehensive Analytical Assessment (CAA) instead of CES.
Key Components of the Streamlined Approach
This new framework proposed by the FDA clarifies situations where CES is unnecessary. For a biosimilar candidate, the following conditions must be met for CES not to be required [1]:
|
Component |
Description |
Importance for the Clinical Research Center |
|
Comprehensive Analytical Assessment (CAA) |
Detailed structural and functional characterization using the most sensitive tools, demonstrating that the biosimilar is highly similar to the reference product. |
Requires a high-tech laboratory and expertise |
|
Pharmacokinetic (PK) Similarity Study |
Comparison of the absorption, distribution, metabolism, and elimination rates of the biosimilar and reference product in humans. |
Critical role of specialized Phase 1 units. |
|
Immunogenicity Assessment |
Evaluation of the risk of immune response formation against drugs. |
Implementation of rigorous immunogenicity monitoring protocols in clinical trials. |
This approach will significantly reduce development costs and time, enabling biosimilars to enter the market more quickly.
Reflections on Turkish and TİTCK Legislation
The Turkish Medicines and Medical Devices Agency (TİTCK) closely follows international standards in biosimilar licensing processes. TİTCK’s “Guidance on Biosimilar Medical Products” (3rd Revision) dated September 2, 2024 [2], while not completely removing CES as a routine requirement as in the FDA’s new draft, adopts a similar scientific principle:
“The scope of clinical studies depends on the scope and results of analytical and non-clinical data. The less uncertainty remains in analytical and non-clinical data, the narrower the scope of clinical studies can be.” [2]
This situation demonstrates that the TİTCK also recognizes the superiority of analytical data and may follow the FDA’s bold step in future regulatory updates. Clinical research centers in Turkey have the potential to host shorter and more cost-effective biosimilar development projects focused on analytical and PK studies by adapting to this global trend.
Implications for Clinical Research Centers
1 Analytics-Focused Studies: Infrastructure should be strengthened for comprehensive CAA and precision PK studies, which will replace traditional Phase 3 CES studies.
2 Speed and Cost-Effectiveness: Developers should be offered clinical data solutions that support accelerated approval pathways aligned with new approaches adopted by international authorities such as the FDA and EMA.
3 Switchability Studies: The FDA’s trend toward eliminating the requirement for “switching studies” will facilitate the market entry of switchable biosimilars.
Conclusion
The FDA’s biosimilar reform is a turning point in the world of drug development. This new approach, which makes biosimilar development processes faster, more cost-effective, and more scientifically grounded, will ultimately provide patients with easier access to life-saving treatments.
Our center will continue to be a reliable and competent solution partner for biosimilar developers in this new era.
References
[1] U.S. Food and Drug Administration. (2025). Scientific Considerations in Demonstrating Biosimilarity to a Reference Product: Updated Recommendations for Assessing the Need for Comparative Efficacy Studies(Draft Guidance for Industry
[2] Türkiye İlaç ve Tıbbi Cihaz Kurumu (TİTCK). (2024).Biyobenzer Tıbbi Ürünler Hakkında Kılavuz (3. Revizyon, IRD-KLVZ-12).