FDA’s inspection backlog: GAO raises concerns as delays mount
Posted 09 March 2021 | By Michael Mezher
FDA’s inspection backlog: GAO raises concerns as delays mount
Mary Denigan-Macauley, PhD
For decades, the Government Accountability Office (GAO) has raised concerns about the US Food and Drug Administration’s (FDA) inspections program. Now, a year after the agency halted most of its foreign and domestic inspections due to the COVID-19 pandemic, GAO warns that the ensuing backlog could take years to clear.
In a new report and testimony before the House Appropriations Subcommittee on Agriculture, Rural Development, Food and Drug Administration, and Related Agencies, GAO Health Care Director Mary Denigan-Macauley, PhD, said that the agency needs to come up with a plan to address the looming inspections backlog and tackle some of its longstanding issues.
FDA conducts three types of inspections: preapproval inspections, routine surveillance inspections and for-cause inspections. For routine surveillance inspections, FDA considers inspections of sites that have never been inspected and those that have not been inspected within five years to be mandatory and prioritizes its remaining resources on inspecting establishments based on risk.
Since declaring that it would halt all but mission-critical inspections, FDA has in part relied on alternative tools, such as inspection reports from foreign regulators, records requests, and product sampling to complement its oversight activities. The agency also has resumed some of its foreign and domestic inspections activities, albeit on a very limited basis.
“While these tools can provide useful information, most do not substitute for an inspection, and FDA will face a backlog as it was unable to complete more than 1,000 of its planned inspections for FY 2020,” Denigan-Macauley said. In January, GAO called on FDA to assess its alternative inspections tools and come up with a plan to deal with the backlog. (RELATED: Inspections: GAO calls on FDA to plan for backlog, review alternatives, Regulatory Focus 1 February 2021).
GAO’s report, submitted as testimony to the hearing, finds that “if inspections continue to be postponed, the backlog of mandatory inspections this will create could both extend the maximum interval between inspections beyond FDA’s five-year policy and reduce the resources available in fiscal year 2022 for inspecting the other highest priority establishments identified by its model.”
“It is a daunting job, and it’s not something that can just be deemed from a document review,” Denigan-Macauley said, noting that inspectors are able to make observations about cleanliness and compliance practices while on-site that would be difficult to glean from alternative tools.
“As it stands now, we remain very concerned that [FDA is] not going to have additional resources to be able to reduce that backlog, so perhaps they have to come up with a different way of looking at what they consider the most important ones to get done first,” they said.
Since making its recommendations in January, GAO notes that FDA has still not fully assessed how its alternative tools can be used to supplement or replace inspections going forward. FDA officials are in the process of conducting that assessment and are reportedly considering the use of remote video and other remote and live interactions with establishments and records to evaluate drug manufacturing operations.
While FDA has said the postponed inspections have not had a significant impact on approval decisions, Denigan-Macauley said that manufacturers are growing increasingly concerned as time goes on. “They said that while it’s true that the impact may not be felt immediately because the inspections for preapprovals are done several months prior, as the pandemic goes on it’s going to have more and more of an impact,” Denigan-Macauley said.
Despite FDA’s insistence, there have been several cases of companies receiving complete response letters (CRLs) or the agency deferring action on drugs and biologics in part due to its inability to conduct on-site inspections. (RELATED: FDA details review timelines as facility assessment-related CRLs pile up, Regulatory Focus 22 December 2020).
Aside from pandemic-related issues, Denigan-Macauley said that FDA’s biggest challenge is to hire and train investigators, something that has challenged the agency for years. (RELATED: Foreign Drug Inspections Decline as FDA Hiring Struggles Continue, Regulatory Focus 10 December 2019)
“Most importantly, they have got to figure out how to fill their vacancies. Even if you poured more money at them, I don’t think that would solve the problem because they’re having a challenge getting investigators to even do the work,” Denigan-Macauley said.
Despite FDA’s testimony last June that it would fill all investigator vacancies by the end of the year, there were still open investigator positions as of December, Subcommittee Chairman Sanford Bishop (D-GA) said, questioning whether hiring and training new investigators was a priority for FDA. (RELATED: FDA defends its oversight of foreign drugs amid Senate, GAO criticism, Regulatory Focus 3 June 2020).
“Something isn’t quite working and that’s what we’re still trying to figure out. Because there are still vacancies year after year,” Denigan-Macauley replied, adding that GAO has “serious concerns that the pandemic will exasperate … fulfilling those vacancies, particularly for those working in the foreign offices because a lot of individuals are now fearful of traveling and being stationed in India and China.”
While more money might not necessarily solve all of FDA’s inspection woes, the agency is set to get some additional funding for inspections that were delayed or cancelled due to the pandemic in the COVID-19 relief bill expected to pass in the House on Wednesday. (RELATED: House committee proposes $500M in COVID funding for FDA, Regulatory Focus 10 February 2021).
FDA faces significant challenges in conducting the inspections it has already postponed and the new inspections it will need to conduct to support product approvals and keep pace with its surveillance inspections policies.
The agency announced in July 2020 that it would resume domestic inspections using a rating system to determine whether it was safe to conduct inspections in a particular county. (RELATED: FDA looks to resume domestic inspections this month, Regulatory Focus 10 July 2020). “According to FDA’s area rating data, as of 3 December 2020, conditions were appropriate for conducting routine surveillance inspections in 49 US counties, with regulatory activity limited to mission critical inspections only in the more than 3,000 remaining counties,” according to the GAO report.
From March to 1 October 2020, the agency conducted just three foreign and 52 domestic inspections, compared to hundreds of foreign and domestic inspections it would typically conduct over the same period.
More recently, FDA restarted its inspections programs in China and India, though the agency “has not set a date for resuming routine foreign surveillance inspections in all countries.”
According to GAO, FDA conducted nine preapproval inspections in China from 26 October 2020 to 14 January 2021 but did not conduct any routine surveillance inspections during that time. In India, FDA conducted just two inspections through 25 February 2021, after resuming operations in January.
The GAO report also gives insight on the regulatory actions FDA has taken against foreign drug manufacturers based on the use of its alternative tools. Between March and December 2020, FDA placed 64 foreign establishments on import alert, one based on issued identified in a foreign inspection report, nine for refusing records requests or for deficiencies identified during records reviews and 54 based on product sampling.
In addition to the challenges posed by COVID-19, Denigan-Macauley told members of the subcommittee that FDA’s foreign inspections program faces “unique challenges” that have gone unaddressed for years. Those challenges include the fact that the agency typically provides advanced notice of inspections to foreign establishments, compared to its practice of conducting unannounced inspections in the US, and the fact that the agency relies on the establishments themselves for translation services. During the COVID-19 pandemic, FDA has resorted to preannouncing all inspections as a safety measure.
“FDA continues to rely on the establishments for translations and still provides up to three months advance notice for most [foreign inspections], giving manufacturers the chance to fix problems before an investigator even arrives,” Denigan-Macauley said, adding that investigators have little flexibility to extend foreign inspections and are often tasked with inspecting massive facilities on their own.
Pressed by Subcommittee Ranking Member Jeff Fortenberry (R-NE) to give the agency a letter grade for its inspections program, Denigan-Macauley said, “It’s certainly not the failing grade that we would have given it two decades ago,” opting to give the agency a lackluster grade.
“The fact that inspections are going down that they have continued oversight problems overseas, I think at best we could say they are at a C,” Denigan-Macauley said.
Gilead Declines 'Rare Disease' Status For Experimental Coronavirus Drug
March 25, 20203:48 PM ET
After the Food and Drug Administration granted Gilead Sciences orphan drug status for its experimental drug remdesivir on Tuesday, Gilead asked that the agency rescind that status Wednesday.
Bloomberg/Bloomberg via Getty Images
In a surprising turnabout, drugmaker Gilead Sciences asked the Food and Drug administration on Wednesday to rescind orphan status for remdesivir, the company's experimental coronavirus treatment.
The agency granted this status to remdesivir on Monday, prompting a backlash from public health and consumer advocates. Orphan drug designation is intended to spur development of drugs for rare diseases by bestowing drugmakers with tax breaks, FDA fee waivers and seven years without generic competitors.
Although this isn't the first time a company has asked for an orphan designation to be rescinded, it's rare, says James Love, director of Knowledge Ecology International, a non-profit public interest group.
"Gilead must have been feeling the heat," Love says. "I think it's embarrassing to take something that's potentially the most widespread disease in the history of the pharmaceutical industry and claim it's a rare disease."
For its part, Gilead said it could proceed to develop the drug quickly without the special regulatory status.
"Gilead is confident that it can maintain an expedited timeline in seeking regulatory review of remdesivir, without the orphan drug designation," the company wrote in a statement. "Recent engagement with regulatory agencies has demonstrated that submissions and review relating to remdesivir for the treatment of COVID-19 are being expedited."
To get orphan status, a drug company must show its drug serves a population of fewer than 200,000 people in the United States, "at the time of the submission of the request for orphan-drug designation." Gilead's latest statement indicates that this was early March.
Domestic COVID-19 cases are expected to surpass that threshold. As of Wednesday afternoon, there were more than 60,000 confirmed cases of COVID-19 in the U.S.
Orphan drugs are among the most expensive in this country, in part because they are shielded from from generic competition for longer than other prescription medicines.
Knowledge Ecology International had been preparing to file a citizen petition to push the FDA to reverse its decision on remdesivir, Love says. Now, it won't have to.
"The facts and circumstances should have given the FDA the authority to have rejected the application, which they did not do," the says.
The FDA confirmed to NPR that it has "received and processed" Gilead's request.
original content ©2020 to 2021 by Alan Robert Ross
Founder, Trust Intelligence
The foregoing is not investment advice.