Bioequivalence Studies for Submission in ANDAs during the COVID-19 Pandemic
FDA recognizes that the COVID-19 pandemic may impact the conduct of bioequivalence studies intended for submission in Abbreviated New Drug Applications (ANDAs). For example, challenges may arise from quarantines, site closures, travel limitations, interruptions to the supply chain for the proposed generic product or the reference listed drug product, or other considerations if site personnel or study subjects become infected with COVID-19. In addition, the process of interrupting and restarting bioequivalence studies for ANDAs may require protocol revisions and impact the collection of information needed to establish bioequivalence.
Prioritize Protection of Participants
For bioequivalence studies intended for submission in ANDAs that have been impacted by COVID-19, ANDA applicants should prioritize the protection of the study participants as they consider conducting these studies during the pandemic. For considerations regarding the conduct of in vivo bioequivalence studies during the public health emergency, please consult the final guidance Protecting Participants in Bioequivalence Studies for Abbreviated New Drug Applications During the COVID-19 Public Health Emergency (January 2021), available at COVID-19-Related Guidance Documents for Industry, FDA Staff, and Other Stakeholders.
For ANDAs that have already been submitted to FDA, ANDA applicants should direct questions to the Regulatory Project Manager for their ANDA.
- For ANDAs that have not yet been submitted to FDA, prospective applicants should submit specific questions related to their impacted bioequivalence studies, including questions about protocol revisions and information collection, via the controlled correspondence process or other appropriate avenues as discussed below.
- Prospective applicants may submit specific questions related to proposed modifications of study protocols, including modifications to incorporate adaptive designs that may allow recruitment of additional subjects or alternative statistical analysis plans as supported by modeling and simulation. The FDA guidance “Adaptive Designs for Clinical Trials of Drugs and Biologics” provides general scientific principles on adaptive designs but does not specifically address bioequivalence studies in support of ANDAs. A recent article presents a survey summary of bioequivalence (BE) studies with adaptive designs in ANDAs, and discusses the challenges and potential opportunities for implementing adaptive designs for BE studies on generic drugs. Please note that the opinions expressed in this article are those of the authors and should not be interpreted as the position of the U.S. Food and Drug Administration. If submitting questions, FDA encourages prospective applicants to provide detailed information including your proposed plans, rationale, and justification supporting your proposal when communicating with the agency. For additional information on the controlled correspondence process, please consult the final guidance Controlled Correspondence Related to Generic Drug Development (December 2020). OGD will prioritize responses to controlled correspondence for COVID-related questions. In some cases, a pre-ANDA meeting request may be appropriate, e.g., for complex products. Please consult the final guidance Formal Meetings Between FDA and ANDA Applicants of Complex Products Under GDUFA (November 2020).
- Prospective applicants may submit general questions related to the impact of COVID-19 on bioequivalence studies to email@example.com.
- Prospective applicants may also notify FDA via firstname.lastname@example.org of any bioequivalence studies that have been interrupted. Please include the name of the drug product, the study design and the point of interruption. This will help FDA identify any need for additional information or guidance on these matters.
FDA may update this site, as appropriate, to provide additional information related to the impact of the COVID-19 pandemic on the conduct of bioequivalence studies intended for submission in ANDAs based on the inquiries that FDA receives.
More information on Coronavirus (COVID-19) related to drugs.