US FDA Doesn’t Want ANDAs With Facilities Not Ready For Inspection Even Though It Can Accept Them
Executive Summary
An agency official said the GDUFA III provision hopefully will be used for only a small number of ANDAs. Pink Sheet charts the approval times and first-cycle clearances over the course of the generic user fee program.
Generic drug sponsors now can file an ANDA with facilities that are not ready for inspection, but the US Food and Drug Administration is not necessarily suggesting they should.
The new generic drug user fee agreement allows the agency to set a goal date for ANDAs that include facilities not ready for inspection, rather than refuse to file them. But Rakhi Shah, associate director for science and communications in the Office of Pharmaceutical Manufacturing Assessment, which is part of the FDA Center for Drug Evaluation and Research’s Office of Pharmaceutical Quality, said the agency does not want that issue to become popular.
“We hope that those cases will be as less as possible,” Shah said during the FDA Generic Drugs Forum last month. “We hope that the applicant makes that decision [to] really not send us the application if [the] facility is not ready or is not going to be ready because no substantial review will take place until month 15.”
Under GDUFA III, ANDAs with facilities that cannot be inspected will receive a 15-month goal date, five months longer than the standard assessment time. However, the agency will not conduct a substantive assessment of the application. Only a filing review can be completed until the agency receives an amendment certifying all facilities are ready for inspection.
During a question-and-answer portion of the Generic Drugs Forum, Shah was asked why a sponsor would choose to submit an ANDA with facilities not ready for an inspection knowing the substantive assessment would not begin. She responded that “is a great question to be asked to the applicants who would send us those [facility not ready] submissions.”
“We had seen some cases so that’s why the language was included in GDUFA III,” Shah said. “We hope this situation will occur very, very [rarely].”
If the amendment certifying the facilities ready for inspection is not received 30 days before the end of the 15-month goal, the date will be extended another 15 months and FDA staff will begin the substantive assessment.
The agency committed to act on 90% of those applications by the end of the 30-month period.
Once the amendment stating facilities are ready for inspection is received, the agency could impose an eight- or 10-month goal from that point if a priority or standard assessment, respectively, is provided. (Also see "US FDA Begins Implementing New User Fee Programs, But What About The Actual Fees?" - Pink Sheet, 4 Oct, 2022.)
Move Could Help Dent Average Approval Times
The move seems intended to help reduce the overall time to approval for generic drug applications and by extension, help lower drug costs.
The quarterly mean time to full approval was on average nearly 34 months since GDUFA II launched in October 2017. By allowing the application to be filed and then amended when all facility information is available, the time to approval could be shortened, compared to refusing the application and requiring a resubmission.
A refuse-to-file action does not prompt another assessment cycle because officially the cycle never began. But an FDA analysis found that applications incurring an RTR tend to require multiple cycles before approval. (Also see "Want To Avoid A Refuse-To-File? Submit ANDA In English, FDA Says" - Pink Sheet, 3 Jan, 2018.)
At the same time, the agency wants applications free of mistakes that hinder the assessment. The FDA has little patience for typos and other problems in order to encourage application quality. (Also see "FDA Rolls Out Zero-Tolerance Policy On ANDA Typos" - Pink Sheet, 3 Oct, 2017.)
The story continues after the chart…
GDUFA III Goal To Maximize Assessment Cycle Efficiency
CDER Principal Deputy Director Jacqueline Corrigan-Curay said during the Forum that one of the priorities of GDUFA III is to maximize the efficiency of each assessment cycle.
Options include extending ongoing cycles if the application is close to approval, such as for labeling issues or “a scientific issue that comes up and a sponsor asks for a more comprehensive scientific discussion mid-cycle,” Corrigan-Curay said.
Ideally, the FDA and industry would like ANDAs to be approved after their initial assessment, but those remain rare. First-cycle approval rates are moving higher, yet represent a fraction of all ANDA approvals. (See charts below.)
The imminent approval process, where the agency would miss a goal date if an approval was expected, was implemented during GDUFA II. If assessors believe they can complete a full or temporary approval within 60 days after the goal, the agency could let the date pass without action.
Imminent approvals started slowly, but seemed to gain more traction during the COVID-19 pandemic. Through February, the agency had reported 39 imminent actions in fiscal year 2023, the first year the metric has been included in publicly available data. (Also see "‘Imminent’ Generic Approvals Expected To Help US FDA Meet On-Time Review Metric Retroactively" - Pink Sheet, 12 May, 2021.)
Labeling discipline review letters will not be issued until later in the assessment cycle in GDUFA III to avoid approval delays from last-minute reference product labeling changes. A goal date extension also is allowed to resolve a last-minute labeling adjustment. (Also see "FDA’s ‘Imminent Action’ Policy Likely Not Best Path For ANDAs To Address Late Brand Label Changes" - Pink Sheet, 26 Jul, 2022.)