Remote Inspections: Stakeholders Seek Clarity As Some At US FDA Struggle With Process
Executive Summary
Some lawmakers want FDA to prioritize in-person visits, but others are complaining that more remote inspections are needed because approvals are being delayed.
Some US Food and Drug Administration staff continue to struggle with remote inspections as stakeholders press for greater use of the pandemic work-around to reduce a growing backlog of facilities waiting for the visits.
Lawmakers wondered during a House Energy and Commerce Health Subcommittee hearing earlier this month how alternative inspection tools can be used more effectively, including for generic and biosimilar facilities. Center for Biologics Evaluation and Research Director Peter Marks said that remote inspections largely have not been successful in his center.
“We are still learning how effective these tools can be by using them,” Marks said during the hearing, which examined the upcoming prescription drug, generic drug and biosimilar user fee reauthorization agreements. “At least at our center we have had some mixed results with using remote inspection technology. So, we are still sorting through this.”
Center for Drug Evaluation and Research Director Patrizia Cavazzoni added that applicability depends on the state of the facility, including its compliance history.
“There are some facilities, including biosimilar facilities but not only those, where because of past history, we determine that we have to do a physical inspection and therefore we are not able to use these alternative methods,” Cavazzoni said. “This is not an issue that applies only to biosimilars, but really all of the drugs under review.”
David Gaugh, Association for Accessible Medicines senior VP of sciences and regulatory affairs, said that the trade association is working with the FDA on its definition of mission-critical as it relates to biosimilar and generic facility inspections. Mission-critical facility inspections have been conducted in-person throughout the COVID-19 pandemic.
Gaugh also said AAM is hoping to meet with FDA officials, likely in March, to discuss how inspections can be restarted “and not restarted slowly but restarted in full blow.”
“We’ve had continued dialogue with them about that on generics and biosimilars and being able to get that and their mission-critical definition,” he said. “If you’re the third or fourth biosimilar to a brand drug then it’s not considered a mission-critical drug and so it doesn’t get its inspection.”
The FDA restarted in-person domestic surveillance inspections on 7 February after a pause due to the spread of the Omicron variant.
Juliana Reed, executive director of the Biosimilars Forum, also said in a recent interview with the Pink Sheet that the group wants to ensure the FDA’s remote inspection policy is consistently applied.
“What we need to see is the agency follow through on their guidance on remote inspections and implement it more robustly,” Reed said.
While some members of Congress have argued in favor of more remote inspections, others are demanding more in-person inspections. In fiscal year 2022 appropriations legislation, House members wrote that the FDA should prioritize physical inspections over other methods, while Senators said remote inspections should be employed to help ensure on-time drug approvals. (Also see "FDA Would Get Less Funding, Different Inspection Priorities Under Senate Legislation Than House" - Pink Sheet, 5 Aug, 2021.)
CDER has used remote inspection tools, which allow the use of cameras, data and other information to avoid some in-person visits. More than 50% of facilities were saved from pre-approval inspections because of alternative approaches each quarter from 1 April 2020 through 30 September 2021.
However, CDER was forced to delay at least 48 application decisions because an inspection was necessary. (Also see "Forty-Eight US FDA Drug Application Decisions Delayed By Pandemic's Deferred Inspections" - Pink Sheet, 5 May, 2021.)
The FDA also wants to resume surprise inspections in India and China this year. (Also see "US FDA Looks To Resume Unannounced Inspections In India And China" - Pink Sheet, 13 Dec, 2021.)
CDER Wants Drug Recall Authority
Cavazzoni also supported adding mandatory recall authority for drugs to the FDA’s enforcement tool set.
Cavazzoni said during the hearing that when hand sanitizers were discovered to contain methanol, rather than mandate a recall, the agency had to work with individual manufacturers to pull products from the market. While many were responsive, some were not, she said.
“Our inability to mandate recalls for most drugs is a real gap for most of us,” Cavazzoni said. “We think that this inability to mandate recalls is an outlier even across FDA products and is also an outlier when we look at the authorities of other major regulatory agencies throughout the world.”
Cavazzoni added that depending on manufacturers to do the right thing in a recall situation can still put the public at risk.
“There may be instances such as what we have seen with the hand sanitizers where it may take weeks for us to persuade the manufacturers and during that time the public are exposed to harmful if not lethal contaminants in drugs and products,” she said.
Mandatory recall authority was included in the America COMPETES Act, a wide-ranging bill intended to strengthen supply chains and invest in scientific research, which passed the House on 4 February. (Also see "US Supply Chain "Elasticity" Pilot Would Get Major Funds In House-Passed Legislation" - Pink Sheet, 7 Feb, 2022.)
House members also inserted a section into fiscal year 2021 appropriations legislation granting mandatory drug recall authority, but the bill was never passed in favor of a continuing resolution. (Also see "US FDA Would Get Mandatory Recall Authority For Drugs Under House Funding Bill" - Pink Sheet, 9 Jul, 2020.)
Congress Gathering Policy Riders For User Fee Bill
The House subcommittee hearing touched on several issues, some of which could foreshadow provisions in the upcoming user fee reauthorization bill.
Members asked Cavazzoni and Marks about accelerated approval, including whether confirmatory trials should be started before the approval is granted, as well as whether the FDA and Centers for Medicare and Medicaid Services consult prior to coverage decisions. Several members were outraged by the CMS decision to restrict coverage for Biogen, Inc. and Eisai Co., Ltd.’s Alzheimer’s drug Aduhelm (aducanumab-avwb) to those participating in a clinical trial.
Marks also indicated he did not think sponsors should receive all of the agency review documents on an application following a complete response letter. (Also see "Complete Response Letters: US FDA Tells Congress Broader Disclosures To Sponsors Could Be ‘Chilling’" - Pink Sheet, 3 Feb, 2022.)
Cavazzoni also said that the FDA wants authority to disclose more inactive ingredient and excipient information in brand drug labels. (Also see "US FDA Seeks Ability To Include More Inactive Ingredient, Excipient Info In Brand Labeling" - Pink Sheet, 14 Feb, 2022.)
Congress must reauthorize the user fee programs by 30 September to avoid an break in funding for the agency. (Also see "GDUFA III Talks Completed; Fees will Fund Inspection, Complex Generic Improvements" - Pink Sheet, 2 Sep, 2021.)