FDA offers guidance on generic drug development during COVID

The US Food and Drug Administration (FDA) on Monday released a new questions and answers guidance for generic drugmakers addressing generic product development and abbreviated new drug application (ANDA) submissions and assessments during the COVID-19 public health emergency.
 
“FDA recognizes that the COVID-19 public health emergency may impact the development of generic drug products, interrupt or delay ANDA applicants’ bioequivalence studies, and impact the submission of ANDAs to FDA for assessment. The ongoing development of generic drugs submitted as ANDAs to the FDA for assessment helps Americans continue to have access to safe, effective generic drugs,” FDA says.
 
The immediately effective guidance features 15 questions and answers addresses questions the agency has received from generic drugmakers throughout the pandemic.
 
The eight questions and answers related to generic drug development “generally assume that bioequivalence (BE) studies … have either been interrupted or have not started due to the COVID-19 public health emergency.” FDA says that such interruptions or delays could impact an applicant’s ability to obtain reference products or could result in reference or test products expiring before BE studies can be completed.
 
In its answers, FDA explains the options available to generic drugmakers in a range of circumstances, including when test or reference product has expired, and addresses its openness to alternative study approaches.
 
In the section on ANDA submissions and assessments, FDA clarifies its approach to receiving and reviewing applications for ANDAs that could be used to help address the COVID-19 pandemic.
 
FDA explains that it will expedite the assessment of such products according to its manual of policies and procedures (MAPP) 5240.3 Rev. 5 Prioritization of the Review of Original ANDAs, Amendments, and Supplements. The agency says it will evaluate ANDAs for priority review at the time of submission and will consider whether the product is being investigated to treat or prevent COVID-19, but not currently labeled for such use or if the drug is labeled to treat or prevent secondary conditions associated with COVID-19.
 
Generics that could be used to address the public health emergency will still be subject to receipt evaluations to ensure they are substantially complete.
 
FDA also says it will generally require ANDAs to include a full complement of batch stability data: “Any deviation from the foregoing recommendations should be accompanied by a scientific justification explaining how the relevant data that is submitted in the application meets the applicable statutory and regulatory requirements. Such justification should be provided in the original ANDA, along with a written statement certifying that the omitted stability data will be provided when it becomes available. If a prospective ANDA applicant intends to submit an ANDA with stability data covering a period of less than 6 months, FDA recommends that the prospective ANDA applicant submit a request via the controlled correspondence pathway.”
 
Furthermore, FDA says it “likely would not receive an ANDA that 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.”
 
FDA will not, however, automatically reject an application if it includes sites that cannot be inspected due to COVID-19-related travel restrictions. FDA says that approval decisions will be based on the totality of information available to the agency, including information obtained via alternative tools detailed in its COVID-19 inspections guidance. (RELATED: FDA issues pandemic inspections FAQ guidance, Regulatory Focus 19 August 2020).
 
FDA also clarifies that it is not able to permit marketing of a tentatively approved ANDA, even if the product could be used to help address the COVID-19 public health emergency.
 
“Under section 505 of the FD&C Act, a drug product that is the subject of a tentatively approved ANDA is not an approved drug and does not have an effective approval until FDA issues an approval after any necessary additional review of the application. Accordingly, there is no mechanism by which FDA can convert a tentatively approved ANDA to final approval and permit marketing until the ANDA meets all the requirements for final approval,” FDA writes.
 
For generic drugmakers worried that inspection delays could delay ANDA approval and potentially impact their eligibility for 180-day generic drug exclusivity, FDA says it will make forfeiture decisions in the context of the specific application. “Whether FDA’s inability to conduct certain inspections will factor into 180-day exclusivity decisions will be determined on a case-by-case basis.
 
FDA