Million A Tegenge1, Iftekhar Mahmood2, Richard Forshee1. 1. Office of Biostatistics & Epidemiology, Center for Biologics Evaluation and Research, Food & Drug Administration, Silver Spring, Maryland. 2. Division of Clinical Evaluation and Pharmacology/Toxicology, Office of Tissue and Advanced Therapies (OTAT), Center for Biologics Evaluation and Research, Food & Drug Administration, Silver Spring, Maryland.
Abstract
INTRODUCTION: Clinical pharmacology studies are one of the major types of regulatory data submitted for review of therapeutic proteins regulated by the Center for Biologics Evaluation and Research (CBER). AIM: The primary objective of the current study is to provide an overview of the role of clinical pharmacology including pharmacokinetics (PK), pharmacodynamics (PD) and exposure-response analysis at CBER. Furthermore, we aim to provide a baseline estimate for the use of quantitative clinical pharmacology studies prior to implementation of FDA's model-informed drug development (MIDD) pilot programme. METHODS: We survey original Biologics License Applications (BLAs) for plasma-derived and related recombinant therapeutic protein products approved by CBER/FDA (2008-2017). RESULTS: There were 37 original BLAs that met our inclusion criteria, and 34 of these products (92%) contained human PK data as part of the biological licensing. The products were broadly classified as coagulation factors (54%), IgG and related proteins (24%), and other therapeutic proteins (22%). Coagulation factor VIII and IX products constitute 32% of the BLAs and indicated for treatment of haemophilia A and B, respectively. Twelve products (35%) used model-based approaches (population PK/PD and exposure-response). Over the past 5 years (2013 to 2017), there is a trend for increased application of MIDD approaches as compared to the previous cohort years (2008 to 2012). CONCLUSION: In conclusion, clinical pharmacology has played a major role in regulatory review of plasma-derived products, and we expect that the application of quantitative methods will further evolve for these products under the FDA MIDD programme. Published 2019. This article is a U.S. Government work and is in the public domain in the USA.
INTRODUCTION: Clinical pharmacology studies are one of the major types of regulatory data submitted for review of therapeutic proteins regulated by the Center for Biologics Evaluation and Research (CBER). AIM: The primary objective of the current study is to provide an overview of the role of clinical pharmacology including pharmacokinetics (PK), pharmacodynamics (PD) and exposure-response analysis at CBER. Furthermore, we aim to provide a baseline estimate for the use of quantitative clinical pharmacology studies prior to implementation of FDA's model-informed drug development (MIDD) pilot programme. METHODS: We survey original Biologics License Applications (BLAs) for plasma-derived and related recombinant therapeutic protein products approved by CBER/FDA (2008-2017). RESULTS: There were 37 original BLAs that met our inclusion criteria, and 34 of these products (92%) contained human PK data as part of the biological licensing. The products were broadly classified as coagulation factors (54%), IgG and related proteins (24%), and other therapeutic proteins (22%). Coagulation factor VIII and IX products constitute 32% of the BLAs and indicated for treatment of haemophilia A and B, respectively. Twelve products (35%) used model-based approaches (population PK/PD and exposure-response). Over the past 5 years (2013 to 2017), there is a trend for increased application of MIDD approaches as compared to the previous cohort years (2008 to 2012). CONCLUSION: In conclusion, clinical pharmacology has played a major role in regulatory review of plasma-derived products, and we expect that the application of quantitative methods will further evolve for these products under the FDA MIDD programme. Published 2019. This article is a U.S. Government work and is in the public domain in the USA.
Authors: Aikaterini Alexaki; Gaya K Hettiarachchi; John C Athey; Upendra K Katneni; Vijaya Simhadri; Nobuko Hamasaki-Katagiri; Puja Nanavaty; Brian Lin; Kazuyo Takeda; Darón Freedberg; Dougald Monroe; Joseph R McGill; Robert Peters; Jacob M Kames; David D Holcomb; Ryan C Hunt; Zuben E Sauna; Amy Gelinas; Nebojsa Janjic; Michael DiCuccio; Haim Bar; Anton A Komar; Chava Kimchi-Sarfaty Journal: Sci Rep Date: 2019-10-29 Impact factor: 4.379
Authors: Tongli Zhang; Ioannis P Androulakis; Peter Bonate; Limei Cheng; Tomáš Helikar; Jaimit Parikh; Christopher Rackauckas; Kalyanasundaram Subramanian; Carolyn R Cho Journal: J Pharmacokinet Pharmacodyn Date: 2022-02-01 Impact factor: 2.745