Bristol Myers Squibb Princeton, New Jersey, United States
Background: The scientific and clinical fronts of Clinical Pharmacology (CP) are continuously and rapidly advancing. Meanwhile, the regulatory landscape is evolving. In 2020 alone, FDA issued six drug-drug interaction drafts or final guidance (1). Additionally, model informed drug development (MIDD) remains as an important initiative for PUDFA IV (2). The coherent integration CP knowledge and regulatory updates will inform and guide the CP strategies in drug development. This work is to comprehensively summarize the PMC/Rs for recently FDA approved original BLAs/NDAs (2020- June 2022). Methods: FDA published data pertinent to PMC/Rs, which were summarized for originally approved BLAs/NDAs (biologic license/new drug applications) from 2020 to June 2022. The prevalence of each PMC/Rs was ranked in the numerical order by CP categories. FDA Project initiatives were considered to gain further understanding of FDA issued PMC/Rs. Results: A total of 38 approved original submissions (out of 85, 45%) were issued with CP related PMC/Rs. Among those, 31 PMC/Rs were in DDI category, 29 in hepatic impairment, 26 in dose optimization, 17 in renal impairment, and 13 in specific populations, and some of the PMC/Rs were recurrent from the same application. Additionally, over the recent years, PMC/Rs for dose optimization have increased and the requests of assessment of PK in the geriatric (>=age of 65) studies were the leading majority for specific populations. Conclusion: Conventional CP studies, such as DDI and hepatic impairment, continuously represent the main body of PMC/Rs. There is a trend of increased number of PMC/Rs related to dose optimization in patients and special populations, reflecting FDA efforts of Projects OPTIMUS and SILVER.
1. Search for FDA Guidance Documents | FDA, accessed Aug 24th, 2021 2. Model-Informed Drug Development Pilot Program | https://www.fda.gov/drugs/development-resources/model-informed-drug-development-pilot-program;
