PII-186 - A SURVEY ON RECOMMENDATION OF FOOD CONDITIONS IN BIOEQUIVALENCE STUDIES WITH PHARMACOKINETIC ENDPOINTS FOR GENERIC ORAL ANTINEOPLASTIC DRUG DEVELOPMENT.

J. Bae¹, T. Tran¹, J. Shon², M. Kim³, S. Borges², K. Li²; ¹ORISE, ²Division of Therapeutic Performance II, Office of Research and Standards, Office of Generic Drugs, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, ³Division of Therapeutic Performance II, Office of Research and Standards, Office of Generic Drugs, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, MD, USA.

Background: Product-specific guidances (PSGs) for oral antineoplastics generally recommend patients as the study population in pharmacokinetic (PK) bioequivalence (BE) studies due to safety concerns. Typically, one BE study is recommended in patients regardless of food instruction in the reference listed drug (RLD) labeling. However, the control of food intake during the BE study may potentially pose challenges in maintaining the patient’s standard of care. This survey aimed to explore the actual practice regarding food conditions in PK BE studies and identify differences between the recommendations in the RLD labeling and their PSGs.

Methods: From FDA PSG databases, PSGs for oral antineoplastics recommending PK BE studies in patients were identified. For each RLD, food instructions from the labeling, food conditions and study population from PSGs, and BE study reports submitted in abbreviated new drug applications (ANDAs) between 2013 and 2023 (if applicable) were collected.

Results: Out of 41 PSGs (41 RLDs, 38 active pharmaceutical ingredients) identified, 14 recommended fasting, three fed, three both fasting and fed, and 21 were silent. The food instructions of 11 PSGs differed from their RLD labeling. Of 41 RLDs, 14 had 81 ANDAs submitted between 2013 and 2023, of which two had ANDAs submitted with biopharmaceutics classification system biowaivers only, eight had PK BE studies only, and four had both. Forty-five ANDAs (12 RLDs) had PK BE studies, of which 17 (six RLDs) enrolled healthy volunteers (HVs). The food condition of PK BE studies in 43 ANDAs were consistent with the PSG recommendations. The PK BE studies in the remaining two ANDAs deviated from their PSGs (either silent or fed only) with one conducting both fasting and fed in HV and one conducting fasting in HV and fed in patients.

Conclusion: This survey identified differences between RLD labeling and PSGs regarding food conditions; however, food conditions appeared to be generally consistent between PSGs and ANDAs with PK BE studies. In addition, there were deviations in study population between PK BE studies in ANDAs and PSGs. Further analyses would provide a better insight into possible PSG revisions to ensure consistency of food condition and study population in PK BE studies for developing generic oral antineoplastics.