Over the course of 2021, lawmakers, government officials and the FDA's top brass have wracked their brains for a solution to the agency's hefty drug manufacturing inspection backlog. The regulator has started to right the ship at home, but abroad, problems persist.
And while much of the attention on the FDA’s backlog has focused on delays in approving new drugs, it also poses problems for those that’ve received write-ups from the regulator, who rely on those inspections to clear warning letters or import alerts.
In its mid-November update to its “roadmap” for inspectional resiliency, the FDA reported 52 new drug application delays because of the agency’s pandemic-related inspection backlog, up from 48 delayed applications reported in May. At the same time, though, the regulator exceeded its expectation for the number of U.S. inspections it could knock out.
So, what’s in store for next year? In terms of domestic manufacturing inspections, it’s possible that the FDA could complete its backlog.
Given the progress the FDA has made at home, “it does seem reasonable to us to assume that because the FDA was able to restart their domestic surveillance inspections in July of this year, that they’ve been able to make some progress on the domestic backlog since we last reported,” Mary Denigan-Macauley, director of healthcare at the Government Accountability Office (GAO), said.
Despite the agency’s inspection improvements at home, it’s a much different story abroad, Denigan-Macauley added. Given the problems the FDA is facing on that front, several of which predate COVID-19, the chances of the FDA whittling down its foreign inspection backlog look slimmer, and “definitely not by next year,” she said. Judy McMeekin, associate commissioner for regulatory affairs at the FDA, said in an email interview, that "throughout the pandemic, we continued to conduct foreign, mission-critical inspections and successfully conducted inspections in nearly 30 countries." She also noted that the regulator is hammering out a strategy to increase foreign surveillance inspections next year.
U.S. course correction
In the U.S., the FDA essentially resumed business as usual in July. By November, it said it had wrapped up 1,139 inspections out of 3,229 outstanding for medical products and devices.
"We exceeded our goal for completing domestic surveillance oversight activities as outlined in the Resiliency Roadmap for FDA Inspectional Oversight Report released in May," McMeekin said.
That includes follow-ups for previous inspections that yielded an official action indicated tag, McMeekin added. Thanks to the agency's risk-based approach, the FDA is now conducting inspections at home that COVID-19 previously scuppered, she said.
The agency doesn't yet have data on the number of additional domestic inspections it's finished since its November update, but it plans to share the information down the line, McMeekin said.
The GAO in January warned that the FDA needed to get its backlog sorted out, lest the regulator hamstring its aim to shift toward exclusively risk-driven surveillance inspections. The office urged the FDA to consider the backlog when laying out forward-looking inspection strategies as well as to figure out alternative inspection tools and whether new options will provide the needed information to supplement the agency’s regular activities or responsibilities when inspections are not possible in the future.
Meanwhile, the issues facing the FDA overseas may be difficult to surmount in 2022 alone. In its latest resiliency roadmap update, the agency did telegraph its intention to forge a plan to resume foreign inspections starting next February. Omicron could disrupt those plans, but there’s no question that the FDA’s resiliency road map is a “step in the right direction,” Denigan-Macauley pointed out.
The foreign surveillance inspections program will rely upon U.S.-based and foreign in-country inspectional staff in places where travel restrictions have lifted, McMeekin explained.
From March to October of last year, the FDA performed only three mission critical inspections overseas, the GAO reported earlier this year. That compares to about 600 foreign inspections the agency conducts annually under normal circumstances.
The situation improved in 2021, but inspection activity was still low. Between April and September 2021, the regulator carried out just 37 foreign drug inspections, three foreign animal drug inspections, four foreign medical device inspections and two foreign biologics inspections.
Like many organizations during the pandemic, the FDA leveraged a mix of digital and remote tools. But while remote inspection tools are a vital resource during the pandemic, in-person inspections are “key” to what the agency does, Denigan-Macauley added. Ultimately, the FDA needs to use those alternative oversight tools—like remote inspections, requesting records and relying on certain other regulators abroad—to supplement, rather than replace its traditional inspections.
On the foreign inspection front, the FDA has been struggling since before the pandemic. Staffing vacancies and language barriers are two big problems, Denigan-Macauley said.
The good news is the FDA is "actively working on these issues," McMeekin said. For example, she pointed to a pilot program the regulator plans to debut in 2022 that aims to "enhance translator capabilities of foreign drug inspections."
She added that investigator staffing levels are key to the agency's mission and that the regulator is actively hiring. It's specifically hunting for "foreign cadre staff" who would be based in the U.S. but travel to foreign countries to conduct inspections, McMeekin said.
Looking ahead, the FDA says it will continue to prioritize “mission critical” work plus other “higher-tiered” inspectional needs such as for cause inspections.
In July, the agency rolled out the FDA Inspectional Affairs Council to develop a multiyear action plan around inspections, information sharing and other processes to “accelerate evaluation and potential integration of new oversight methods and tools.” One of FIAC’s responsibilities is to come up with an agency-wide policy and procedure for Remote Regulatory Assessments.
"We learned through our own experiences thus far and in discussing remote assessment approaches with our foreign counterparts, that remote assessments have presented meaningful technical challenges and require more resources than anticipated," FDA's McMeekin said. Some of those factors include logistical challenges around time zone differences as well as the unavoidable IT problems that come with live-streaming content.
The FDA has relied on these alternative assessments to fortify its oversight during COVID-19, but remote reviews don’t satisfy the in-person requirements for surveillance inspections. By turning to digital, the FDA could make a dent in the number of user fee delays it clears, but it will still be saddled with hundreds of surveillance inspections that require an in-person touch.
"Ideally, inspections supplemented by additional tools, including records requests and remote interactive evaluations, will provide us with the greatest depth of information," McMeekin said. "Information obtained via remote assessments can be used to support regulatory decisions including application approvals and to take regulatory actions including warning letters," she added. Those remote assessments can also "compliment" information received by other mechanisms.
Ultimately, the FDA will need to rely on a healthy mix of the old and new—something that both GAO's Denigan Macauley and FDA's McMeekin pointed out.