Devicemakers Should Prepare for an FDA Focus on Raw Data During Inspections

FDA investigators increasingly are shifting from “top down” inspections focused on policies to “bottom up” inspections that focus on raw data, an industry insider says. Developing an effective game plan for handling inspections and knowing how to interpret certain “red flags” can mean the difference between a good inspection and one that goes south.

“Anyone can write procedures, but the records are where the rubber hits the road,” Timothy Wells, president of Quality Hub, an Orlando, Fla., consulting firm, told a workshop at FDAnews’ Eighth Annual Inspections Summit in Bethesda, Md.

A 24-year FDA veteran, Wells played a key role in drafting the Quality Systems Inspection Technique (QSIT) — a set of 38 questions aimed at helping manufacturers prepare for FDA inspections. But as useful as it was deemed when it was published in 1999, even upper-level FDA management no longer expects agency investigators to strictly follow the volume. This has led to greater inconsistency from investigator to investigator and district to district, Wells said.

Still, certain QSIT paradigms have carried over to the present day. For example, QSIT’s heavy emphasis on management controls of the quality process is a focus investigators maintain today, Wells said. And both QSIT and more recent inspections emphasize corrective and preventive actions.

“All device inspections have a CAPA element,” Wells said. When it comes to fixing problems, manufacturers “shouldn’t expect to get credit if they never opened a CAPA.” He recommends going through the CAPA process on the most common failure modes for each device, even if the absolute numbers are still relatively low. That could help prove a company’s commitment to preventive action, he said.

The FDA also wants to see CAPAs on problems with relatively simple fixes, Wells said. For instance, if a product is being shipped in boxes without sufficient labeling, it’s not enough to just add the labeling; the FDA will also expect a CAPA that shows the company performed a root cause analysis to track back the reasons the unmarked boxes were used.

Wells warned devicemakers that FDA investigators tended to gauge a company’s volume of CAPA reports and MDRs against other companies of similar size. If one manufacturer’s count is vastly lower than its competitors’, the FDA may assume the company is hiding something.

Companies should also be alert to certain “red flags” during an inspection, Wells said. One is a question along the lines of “Did you ship that product?” he said. This could indicate that the investigator doesn’t believe the company’s verification and validation processes sufficiently control for device safety.

And if the fact that a potentially unsafe product was shipped makes it into a post-inspection Form 483, that’s an almost certain signal the FDA plans to pursue an enforcement action against the company, the former FDAer said.

Devicemakers can also get into hot water if they don’t completely document their reasons for not recalling a product with known safety concerns, Wells said. It’s a bad sign if an investigator asks for a signature on an affidavit, used to prove knowledge of noncompliance. If that happens, refuse to sign or initial any part of the affidavit and immediately call a lawyer, he said.

A devicemaker’s risk during an audit could also increase based on its general reputation, its relationship with the local district office and any known or suspected violations of trust, such as lying or hiding nonconforming product. Those issues may take years to overcome, Wells said.

To avoid potential trouble spots, Wells urges devicemakers to plan proactively for inspections. This should include “proof books” establishing that a company has addressed major quality systems areas, such as complaints, systems validation and MDRs, and anything that was covered in a previous Form 483 or warning letter.

A proof book can be “almost a slam dunk,” Wells said. “The inspectors just want to be able to check a box saying you addressed the area. If all your documentation is together, that answers the question.”

Wells also advises manufacturers to have subject matter experts on hand during the inspection to discuss specific procedures. This helps to improve investigator confidence that there is a companywide compliance focus.

And Wells suggests using instant messaging or texting to communicate with others in the company while in conference with the investigator. That way, the “back office” can discreetly be alerted to get documents together or prepare a certain individual to talk to the investigator without interrupting the conversation, he said.

To keep things shipshape between inspections, Wells recommends companies perform “robust” internal audits that involve third parties, if necessary.

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