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Oct. 5 — As the FDA ramps up its use of administrative tools related to pharmaceutical quality issues, companies need to make sure they're ready for agency inspections, a former agency official said Oct. 5.
“No inspection is trivial,” James R. Johnson, a partner with the Washington office of Hogan Lovells US LLP told Bloomberg BNA in an Oct. 5 phone call. Prior to joining Hogan Lovells, Johnson was associate chief counsel for enforcement in the Food and Drug Administration's Office of Chief Counsel.
With regard to international inspections, the FDA is making unilateral decisions on whether drug products can come into the U.S., which can have major business repercussions for a company, Johnson said.
“There's a risk to one bad inspection internationally,” he said, including a potential block on letting any of a company's drug products into the U.S.
Johnson's comments followed up on his presentation at a Sept. 25 Life Sciences/Healthcare Regulatory Media Roundtable in Washington sponsored by Hogan Lovells, where he spoke about issues surrounding pharmaceutical quality and data integrity.
“It's a very busy and hot area right now,” he said at the roundtable.
“You're not seeing huge consent decrees or judicial rulings any more,” he said at the roundable, “but there are moreFDA inspections going on and the consequences are more administrative, particularly internationally.”
The FDA has really ramped up its international inspectional capacities over the past five years, he said, responding in part to the fact that most of the ingredients found in drugs used by U.S. consumers are manufactured abroad now.
As a result, Johnson said there's a particular FDA inspectional focus on active pharmaceutical ingredients (API) manufacturers right now.
The nature of the agency's international inspections also has changed, according to Johnson. “They are faster, real-timeinspections,” he said. “They now have the ability to do multiple international inspections of a facility on a much more expedited schedule and are also now doing more unannounced inspections,” he added.
In addition, FDA administrative actions—in the form of import refusals, import alerts, withdrawing drug approvals or holding pending drug applications—have increased, Johnson said.
Moreover, the consequences of a poor international inspection at one facility can have huge ramifications for a company, Johnson noted, because the standard for refusal and the corresponding burden of proof on the agency—that a drug “may be adulterated, misbranded or otherwise violates the [Federal] Food, Drug, and Cosmetic Act ”—is very low.
“A single bad inspection at an international facility can affect all of the company's U.S. drug imports from that facility and any drug applications that rely on that facility.”
“A single bad inspection at an international facility can affect all of the company's U.S. drug imports from that facility and any drug applications that rely on that facility,” he said.
Indeed, the agency recently rescinded its approval for Sun Pharma Advanced Research Co.'s seizure drug Elepsia XR (levetiracetam extended-release tablets 1000 mg and 1500 mg) (13 PLIR 1430, 10/2/15). The agency said it was revoking the approval because the compliance status of the facility where Elepsia XR was manufactured wasn't acceptable as of the date of the drug's approval.
Another change as a result of the ramped-up international inspections is increased communication and information sharing between the FDA and its foreign counterparts. “You'll often see one following the other,” he said, particularly in the area of import refusals and actions on pending applications.
Another hot issue with regard to the FDA's inspections is an increased focus on electronic recordkeeping at facilities, including monitoring who can edit the records.
The FDA, Johnson said, can act on data failures alone, and isn't necessarily linking them to any manufacturing quality failures. For example, he said, the agency has issued import alerts based solely on data integrity issues.
The industry has concerns about a draft guidance the FDA issued in July on quality metrics issues, he said (13 PLIR 1090, 7/31/15). The draft guidance requests that companies to submit data metrics and considers companies' drugs to be adulterated if the companies don't submit the metrics.
“It's going to be facility and product-specific and likely will require companies to devote immense resources to document creation,” Johnson said.
The FDA could view a company's refusal to submit the metrics as an inspectional refusal, he said, with the attendant consequence of deeming the company's products as adulterated.
Many companies are arguing that the FDA doesn't even have the legal authority to require companies to create additional documents, Johnson said.
“These are going to be huge issues over the next year,” he said, adding it's unclear that the guidance will accomplish what the FDA intends it to do. There are potentially negative unintended consequences that could result from the guidance, he said.
“The fear is that it will pull companies away from quality to do just data metrics,” he said.
Nonetheless, he said, there are potential benefits to the guidance, too, because it gives companies a way to show theFDA's Office of Pharmaceutical Quality (OPQ) that they're putting out high-quality products, and OPQ is going to take that into account.
The OPQ, established by Janet Woodcock, the head of the FDA's Center for Drug Evaluation and Research (CDER), formally opened in January. The office aims to centralize quality review for new drugs and generic drugs, including drug application review, post-approval improvements and surveillance and inspections of global manufacturing facilities (13 PLIR 68, 1/16/15). OPQ is separate from CDER's Office of Compliance.
Ultimately, the FDA wants to concentrate its efforts on high-risk products and facilities, Johnson said, and the FDA views data metrics as an avenue for identifying which companies are lower risk and which ones merit more FDA attention.
The comment period for the guidance has been extended until Nov. 27 and it's expected that there will be a lag time in finalizing the guidance as the agency considers the comments it receives, Johnson said.
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