Generic drugmakers seek clarity on pre-submission facility correspondence

Drugmakers want clarifications on an updated draft guidance the US Food and Drug Administration (FDA) recently released on pre-submission facility correspondence (PFC) for generic drug applications.
 
In December, FDA revised its draft guidance on submitting PFCs for generic drug applicants seeking a priority review of their abbreviated new drug application (ANDA), prior approval supplement (PAS) or an amendment to either submission type in line with the Generic Drug User Fee Amendments (GDUFA III) program. The process can be used by generic drug sponsors to get a priority review goal date for their submission, but the PFC must be submitted two months before they submit their premarket application. (RELATED: FDA revises ANDA facility correspondence draft guidance, Regulatory Focus 2 December 2022)
 
The draft guidance specifically reflects changes to the content, timing and assessment of a PFC within the ANDA program as agreed under GDUFA III. It describes the process generic drug applicants who want priority review should follow to provide complete and accurate facility information before submitting a priority original ANDA, PAS, PAS amendment or ANDA amendment.
 
Stakeholders had until 5 March to raise any issues with the proposed guidance and several have written to FDA to ask for more clarity in several areas.
 
The generic drug lobby group the Association for Accessible Medicines (AAM) and Zydus Lifesciences, an Indian drugmaker, both wrote to FDA to ask for clarification on Table 1 in the draft guidance, which lists facility information that should be included in the PFC for priority ANDA applications.
 
AAM took issue with the fact that FDA continues to ask sponsors to list electronic common technical document (eCTD) modules containing facility information, which it said “seems unnecessary” to determine if a pre-approval inspection (PAI) is needed. The group has complained about the issue to FDA in previous comments.
 
“In comments submitted to the docket on the 2017 Draft Guidance, AAM requested that FDA reconsider whether such a substantial amount of information should be requested and provide a rationale for why the information that is requested is necessary to determine whether to conduct a PAI,” said AAM.
 
The group said FDA does provide some explanation for why certain information is requested in the PFC but argues that the agency’s rationale is flawed and not granular enough for sponsors to fully understand why certain information is being requested.
 
“FDA should critically examine each of the items requested to be provided in the PFC with an eye towards paring down the items to only those that are absolutely necessary for FDA to determine whether an inspection must be conducted,” said AAM. “For each of the items requested to be provided in the PFC, FDA should provide the rationale for why it is necessary.”
 
“If FDA were able to further pare down the information that is needed for a PFC, the PFC process could be used more often to qualify applications for a priority review goal, leading to quicker approvals of safe and effective generic drugs, and increased savings for consumers,” the group added.
 
 
In its comments, Zydus said it understands that the tables presented in the draft guidance are useful for pharmacokinetic end point studies but note there may be products for which the sponsor may have a waiver or conducted different types of studies not taken into consideration by FDA.
 
“In such cases, which table no. from the summary table format prescribed by the FDA for each study type should the applicant submit as part of a complete and accurate PFC,” Zydus asked. “We request to incorporate this detail in the final guidance.”
 
Canadian drugmaker Apotex also took issue with Table 1 and asked for clarity around the application description statement. The company said that not all information required for the Summary of Biopharmaceutic Studies and Associated Analytical Methods section may be ready at the time of PFC submission. Instead, it asked FDA to clarify that sponsors should provide a summary of that information, if available, when filing the PFC.
 
Apotex similarly raised issues with FDA’s statement that complete and accurate PFC includes information for facilities involved in manufacturing processes, including testing; sites or organizations involved in bioequivalence and clinical studies used to support the application; and confirmation that all facilities are ready for inspection.
 
The company also asked for clarification from FDA on the bioequivalence and clinical facilities used to conduct the studies, which the company said do not align with other parts of the guidance.