Key Biosimilar Regulatory Milestones

The development and registration of biosimilars are complex processes that involve numerous regulatory milestones. These milestones are critical to ensuring compliance with national, regional, and international regulations and agency opinions. In this article, we will explore the key regulatory milestones in biosimilar development and registration, highlighting the importance of regulatory intelligence and the challenges faced by companies in this field.

Early Regulatory Milestones

1. Choice of Reference (Originator/Comparator) Product: The selection of a reference product is a crucial step in biosimilar development. This choice determines the basis for the comparability exercise and the data required to establish biosimilarity.
2. Definition of Physicochemical and Biological Characterisation Programme: A comprehensive characterization program is necessary to define the analytical methods and parameters for the biosimilar product. This includes the definition of the manufacturing process, controls, limits, and specifications.
3. Preparation of Investigational Medicinal Product Dossier (IMPD) and Investigator’s Brochure (IB): The IMPD and IB are essential documents that provide detailed information about the investigational product, including its composition, manufacturing process, and clinical trial design.
4. Definition of Non-Clinical and Clinical Development Programme: The non-clinical and clinical development programs outline the studies required to demonstrate the safety and efficacy of the biosimilar product. This includes the design of clinical trials and the analysis of data.

Advanced Regulatory Milestones

1. Successful Conduct of Scientific Advice (SA) with EMA (One or Several): Scientific Advice meetings with the European Medicines Agency (EMA) are critical in gaining clarity on regulatory requirements and ensuring compliance with guidelines. These meetings help companies refine their development plans and address any concerns raised by the EMA.
2. Consensus with EMA Regarding the Comparability Exercise, Data to Establish Biosimilarity: The comparability exercise is a key aspect of biosimilar development. Companies must demonstrate that their product is highly similar to the reference product in terms of quality, safety, and efficacy. This requires extensive data and analysis.
3. Set Up of Expert Medical and Scientific Writing Team: A dedicated team is necessary to prepare high-quality regulatory submissions, including the Investigational New Drug (IND) application and the Biologics License Application (BLA).
4. Definition of Calendar and Allocation of Resources for Writing of CTD Modules: The Common Technical Document (CTD) is a standardized format for submitting regulatory applications. Companies must allocate sufficient resources to prepare these modules and ensure timely submission.

Final Stage Regulatory Milestones

1. Pre-Submission Meeting with EMA; Agreement on Critical Issues: A pre-submission meeting with the EMA is essential to discuss critical issues, such as immunogenicity data, extrapolation of safety/efficacy data from different indications, and justification of indications. This meeting helps companies address any concerns and refine their submissions.
2. Final Draft of Risk Management Plan and Summary of Product Characteristics: The Risk Management Plan (RMP) and Summary of Product Characteristics (SmPC) are critical documents that provide detailed information about the biosimilar product, including its safety profile and intended use.
3. eCTD Compilation, Publishing, and Quality Check: The electronic Common Technical Document (eCTD) is the standard format for submitting regulatory applications. Companies must ensure that their submissions are accurate, complete, and compliant with regulatory requirements.
4. Dossier Submission via eSubmission Gateway (and Common Repository / CESP): The final step in the regulatory process is the submission of the dossier via the eSubmission gateway and the Common Repository / CESP. This ensures that all required documents are submitted electronically and in compliance with regulatory requirements.

Conclusion

Biosimilar regulatory milestones are critical to ensuring compliance with national, regional, and international regulations and agency opinions. Companies must be up to date with regulatory requirements and agency opinions to avoid delays and financial losses. High-quality regulatory work is essential for compliance and the successful development of biosimilar products.

References

1. Biosciencetoday.co.uk. (n.d.). Biosimilars – What are the critical regulatory milestones during development and registration? Retrieved from https://www.biosciencetoday.co.uk/biosimilars-critical-regulatory-milestones-development-registration-2/
2. Ophthalmology Times. (2024, February 29). Cardinal Health details milestone year in biosimilars. Retrieved from https://www.ophthalmologytimes.com/view/cardinal-health-details-milestone-year-in-biosimilars
3. FDA. (n.d.). Biosimilars Action Plan. Retrieved from https://www.fda.gov/drugs/biosimilars/biosimilars-action-plan
4. TOPRA. (2019, February). Regulatory complexities and challenges of biosimilars. Retrieved from https://www.topra.org/topra/topra_member/pdfs/CPD-February-2019-v2.pdf
5. Cardinal Health. (2022). 2022 Biosimilars Report: The U.S. Journey and Path Ahead. Retrieved from https://www.cardinalhealth.com/content/dam/corp/web/documents/Report/cardinal-health-2022-biosimilars-report.pdf