FDA Issues Guidance on Generic Development and Submissions During Pandemic

The FDA released Q&A guidance yesterday on bioequivalence (BE) studies for generic drugs and abbreviated new drug application (ANDA) submissions during the COVID-19 pandemic.

The guidance reminds applicants that the agency is prioritizing reviews of generics that could help address COVID-19. At the time of submission, the agency will gauge whether an application is for a drug being investigated to treat or prevent COVID-19 but is not labeled for such a use, or for a drug being used for its labeled use to treat or prevent secondary COVID-19 conditions and will decide on priority review based on its assessment.

For batch stability data, generic applicants should generally provide three pilot-scale batches or two pilot-scale and one small-scale batch with accompanying accelerated and long-term stability data, the agency said. The data should cover a period of no less than six months and come from three time points. If six months of accelerated data demonstrate a significant attribute change or failure in one or more batches, the agency expects applicants to include six months’ worth of intermediate stability studies at the time of submission.

Applicants that deviate from the batch stability data recommendations should include a scientific justification in their submission, explaining how the data meet statutory and regulatory requirements, along with a written statement pledging that the omitted stability data will be provided when it becomes available, the agency said.

Acknowledging that BE studies have faced interruptions and delays due to the pandemic and that applicants have had difficulty in obtaining reference products, which are in most cases the reference listed drug (RLD), the agency said it will generally not accept an ANDA if it does not contain completed BE study data.

“An ANDA containing only partial data at the time of submission on the grounds that the applicant cannot complete bioequivalence studies due to the COVID-19 public health emergency does not constitute an acceptable alternative approach that complies with … regulations,” the FDA said. “An ANDA with only partial data would not, on its face, contain information that purports to show-that the proposed generic drug product is bioequivalent to the RLD.”

The agency also offered advice on what to do if a BE study’s test product batch expires during the pandemic. For example, it recommends manufacturing additional test product, stating that generally, it’s permitted for prospective applicants to do so to resupply their studies when they adhere to certain conditions. The new batch should be manufactured using the same conditions as those used in full-scale production and its size should be based on the recommendations in the agency’s May 2014 ANDAs: Stability Testing of Drug Substances and Products, Questions and Answers guidance.

When a test product batch expires after in vitro BE studies but before the in vivo pharmacokinetic (PK) BE study can be finished, a new batch should be manufactured. This new product should be used in the in vivo PK BE study and for repeat in vitro BE studies, the FDA recommended.

The FDA noted that it has made no exceptions for tentative approvals — which are granted when an ANDA meets all requirements but faces unexpired patents or exclusivities — during the pandemic, even if they are for drugs that could help address COVID-19.

Read the full guidance here: www.fdanews.com/04-05-21-Guidance.pdf. — James Miessler