PI-001 - A LANDSCAPE SURVEY FOR THE PRESENTATIONS APPROVED FOR SUBCUTANEOUS PROTEIN PRODUCTS.

P. Huang^1,2,3, Z. Li⁴, Y. Wang⁵; ¹Purdue University, Purdue University, West Lafayette, IN, USA, ²Oak Ridge Institute for Science and Education (ORISE), Oak Ridge, TN, USA, ³U.S. Food and Drug Administration, Silver Spring, MD, USA, ⁴U.S. Food and Drug Administration, Silver Spring, MD, USA, ⁵U.S. Food and Drug Administration, Silver Spring, MD, USA.

Background: Drug-device combination products have various presentations, such as vial, prefilled syringe (PFS), and autoinjector (AI). AIs are expected to reduce pharmacokinetic variability compared to PFS, enhancing safety and self-administration, thus improving patient compliance with subcutaneous (SC) drugs. To explore bridging strategies across presentations, we surveyed Center for Drug Evaluation and Research (CDER)-approved biological license applications (BLAs) to create a database of SC BLAs. This database will identify challenges in presentation development and BLAs with potential for PFS or AI development, ultimately enhance our understanding of SC therapeutic protein presentation development.

Methods: To identify SC BLAs with vials, PFS, and AI, we obtained a list of 351(a) BLAs from FDA’s Purple Book from 1975 to 2024. We extracted relevant information on each device presentation, including protein structure, concentration, syringe size, and injection volume, from drug labels on the Drugs@FDA website. Device names were obtained from the Container Closure System document in regulatory submissions, and we summarized the findings on product presentations for these BLAs.

Results: Our survey of CDER-approved BLAs identified 121 products with the presentations of vial (n=67, 55.4%), PFS (n=31, 25.6%), and AI (n=23, 19%). Specifically, there were 39 vial-only, 15 AI-only, and 16 PFS-only products. Additionally, 8 products had both vial and PFS, 15 had both AI and vial, and 17 had both AI and PFS, with 5 featuring all three. These products covered 7 therapeutic areas: cardiometabolic and endocrine disorders (n=60), cancer (n=9), infectious diseases (n=2), immunology and inflammation (n=34), neuropsychiatric (n=9), genetic disorders (n=2), and others (n=9). Most PFS and AI products used 1 mL syringes, and some using 2.25 mL syringes.

Conclusion: Fifty-six BLAs have approved AI presentations, with 30 cardiometabolic and endocrine disorders and 19 in immunology and inflammatory diseases. More BLAs have developed PFS and AI in the past decade. The database will evaluate presentation development strategies and identify products with approved PFS but no AI for further follow-up. We also examined common AI device platforms approved for SC therapeutics to aid future research into platform-specific bridging strategies for AI development.