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Quality Concerns to Resurface as FDA Resumes Foreign Inspections (1)

March 17, 2022, 9:25 AMUpdated: March 17, 2022, 5:21 PM

The robustness of the FDA’s foreign inspections program will get a renewed focus as the agency resumes global surveillance activities following a pandemic pause.

The Food and Drug Administration brought back domestic surveillance inspections in February and plans to begin conducting foreign prioritized inspections in April.

As the FDA addresses a nearly two-year inspection backlog, attorneys say the agency should also use this moment to address repeated complaints with its foreign inspection practices. They argue that boosting agency staff, utilizing unannounced inspections, and hiring more independent translators can lead to more accurate FDA reviews.

“One of the biggest problems here is that sometimes these inspections just weren’t meaningful enough,” said John Serio, a partner at Withers who counsels manufacturers and distributors of FDA-regulated products. “Over the years, there has been some real problems with quality in some of these plants.”

The FDA is responsible for conducting both domestic and foreign inspections on manufacturers and distributors of drugs and medical devices.

At the onset of the Covid-19 pandemic, the FDA prioritized on-site evaluations it deemed “mission-critical inspectional work.” The FDA began transitioning back to standard operational levels for domestic surveillance inspections in July 2021 and by November had conducted more than 1,100 inspections. Foreign inspections, on the other hand, mostly remained on hold, with the agency conducting just 124 across 23 countries between April and September 2021.

A Government Accountability Office report in February said the FDA has improved its oversight on foreign drug manufacturing over the past 20 years, but issues with workforce retention and maintaining a regular inspection timeline have grown as more medical product manufacturing has moved overseas.

Some attorneys that counsel international clients say the FDA should use more remote surveillance activities and ask for help from third-party auditors to conduct on-site inspections. Others argue that only in-person inspections conducted by FDA officials can meet the standard necessary for product approvals.

FDA spokesperson Audra Harrison said the agency is developing an “unannounced foreign inspection program as the FDA increases recruitment and retention efforts for the FDA’s foreign workforce.”

Staffing, Translator Woes

Workforce shortages have long plagued the FDA, especially in its foreign inspections program.

“Foreign inspection work is challenging, requiring the investigator to work independently in a foreign establishment under constrained time frames,” according to the GAO. The FDA’s foreign inspection workforce is mostly U.S.-based, with some investigators assigned to foreign offices.

The GAO said the foreign drug inspection cadre has “struggled” to stay fully staffed, in part because of “hardships related to the frequent travel overseas.” Cadre members usually take six three-week foreign trips each year, traveling on flights of 14 hours or more to India, China, and other countries to conduct in-person inspections.

“The nature of the work is very isolating,” Serio said. “You’re in foreign countries, you’re dealing with foreign-speaking people. And not everybody can be an inspector; you have to have a subject matter expertise.”

The FDA also often needs translators to help review the various reports provided by foreign-based companies. The FDA has relied on translation services from either the facility being inspected or staff in the FDA’s closest local office. Translation services is one area the FDA is targeting for improvement, the spokesperson said.

“Having done a number of inspections in Asia,” records can be difficult to understand, and “you too heavily rely on the translator,” said Dennis Gucciardo, a partner at Morgan Lewis who counsels medical device manufacturers on FDA regulations. “When you translate records, it is a story, and it depends on how the translators view it. Some language colloquialisms are not equivalent and, of course, it can lead to confusion.”

The FDA plans to launch a pilot program focused on increasing its connections with independent translators, including through a partnership with the State Department. The GAO said the agency “has not fully developed its plans for how the pilot will be designed.”

Surprise Inspections

If a facility is notified of an inspection ahead of time, it can harm an FDA inspector’s ability to get transparent information about a company’s standard operating practices.

The FDA’s domestic inspections aren’t typically announced beforehand, which pushes facilities to constantly follow the agency’s manufacturing standards, the GAO said. Foreign facilities, on the other hand, are usually given advance notice by the FDA, raising “concerns about their equivalence to domestic inspections,” the GAO said.

“There is nothing that keeps manufacturers on their toes as to an unannounced inspection always being present,” Serio said. “If you always have the threat of an inspector walking in your facility, I think you’re a little bit more vigilant as to making sure that plant is meeting all regulations at all times.”

Conducting unannounced inspections in other countries is “very hard to do,” Gucciardo said. There are logistics that need to be worked out, including getting approvals from local governments, he said.

The FDA plans to start a pilot program to analyze the benefits and weaknesses of unannounced foreign inspections, but specific details on the initiative’s design weren’t finalized as of September 2021, according to the GAO.

Pandemic Lessons

Policy watchers say the pandemic highlighted a need for the FDA to be more flexible so it can conduct foreign facility reviews in the event of public health emergencies.

With the “technology that is available now,” there is “very little that would be missed by using virtual inspection as opposed to an in-person inspection,” Douglas Farquhar, an attorney at Hyman, Phelps & McNamara PC, said.

On Capitol Hill, Reps. Morgan Griffith (R-Va.) and Peter Welch (D-Vt.) have introduced a bill (H.R. 7006) that would help the FDA address backlogs caused by an inability to conduct in-person inspections. The legislation would authorize the FDA to accept records in some cases to satisfy preapproval or risked-based surveillance requirements.

“When we don’t have inspectors, we were already way behind in inspecting some of these facilities, whether they be in Europe or particularly in Asia,” Griffith said in a House health subcommittee hearing Thursday. He added that while in-person inspectors would be preferred, remote alternatives are “better than nothing.”

The FDA “has begun a multi-year modernization effort” that includes “remote approaches,” the FDA’s Harrison said.

She added, though, that the FDA believes “remote interactive evaluations do not replace inspections, and that there are situations where only an inspection is appropriate based on risk and history of compliance with FDA regulations.”

The best way to conduct reviews is to see a company’s everyday practices in action, said Jacqueline Berman, a partner at Morgan Lewis who advises drugmakers.

“The point of an inspection is to see how the facility is operating under real-world conditions,” Berman said.

(Updates with details of related legislation in 24th and 25th paragraphs. )

To contact the reporter on this story: Celine Castronuovo at ccastronuovo@bloombergindustry.com

To contact the editor responsible for this story: Fawn Johnson at fjohnson@bloombergindustry.com