FDA eyes adaptive designs for BE studies impacted by COVID-19
The US Food and Drug Administration (FDA) is looking to adaptive designs to salvage in vivo bioequivalence (BE) studies that have been disrupted by the COVID-19 pandemic.FDA acknowledged the impact that the public health emergency could have on BE studies early in the pandemic and in April 2020 the agency created a webpage with information for abbreviated new drug application (ANDA) sponsors noting that protocol revisions may be required for studies that are interrupted because of quarantines, site closures, travel restrictions or supply chain disruptions.
“Due to the challenges posed by the COVID-19 public health emergency on participation in BE studies, an adaptive study design may be a useful protocol revision for ANDA applicants,” FDA writes. “For example, an adaptive design may allow for additional subjects to be included in response to a larger than usual dropout rate.”
FDA has received numerous questions from generic drugmakers throughout the public health emergency inquiring about protocol revisions to their BE studies. In an update to its webpage on BE study submissions during the pandemic, FDA tells prospective ANDA applicants to submit specific questions on protocol revisions through controlled correspondence.
The agency refers applicants to its guidance Adaptive Designs for Clinical Trials for Drugs and Biologics for an overview of the scientific principles for adaptive designs but notes that the guidance does not specifically touch on BE studies. (RELATED: FDA finalizes guidance on adaptive trial designs, Regulatory Focus 2 December 2019).
FDA also directs ANDA applicants to a recent perspective by staff at the Office of Generic Drugs and the Office of Biostatistics within the Center for Drug Evaluation and Research that explores the possibility and application of adaptive designs to BE studies. The agency is careful to note that “the opinions expressed in the article are those of the authors and should not be interpreted as the position of the [FDA].”
“The COVID-19 pandemic has posed unprecedented challenges to conduct in vivo BE studies and may have led to study interruptions that can lead to using multiple batches in a single study due to batch expiration, partial data due to patient drop out, or truncated [pharmacokinetic] PK curves. Under these circumstances, adaptive designs and model-based analysis can be useful to support protocol revisions by generic applicants,” the authors write.
FDA also says it will prioritize responses to controlled correspondences for COVID-related questions and says that in some instances a pre-ANDA meeting request may be appropriate.
FDA