Beware of FDA Multisite Inspections

Recently, I came across an FDA regulatory situation you do not see too often. On the same day, FDA sent two teams of field investigators into two geographically different sites of the same company to conduct a QSR/cGMP (21CFR820) inspection. An FDA inspection is always a stressful experience but having two simultaneous inspections certainly raises the pressure on the company even more.

Why would the FDA decide to use this simultaneous inspection approach? This reminded us of another similar situation that mdi was involved with once before. This was many years ago but then FDA methods do not change much.

In that case, our client was a company that had three separate divisions. At different times, FDA had conducted inspections of each of these divisions. Each time, FDA inspection resulted in the Form-483 (List of Inspectional Observations) that showed that the company had systemic problems in complying with the QSR regulations.

While the company attempted to respond to the 483s and proposed certain corrective actions, FDA felt these were not sufficient to properly address the QSR noncompliance. FDA was willing to take additional regulatory actions and issued a warning letter to the company reiterating their initial 483 observations as well as FDA’s dissatisfaction with the proposed corrections.

This is when the company reached out to us to request assistance with getting out of this increased FDA enforcement. When we got involved, we worked with the company to respond to the FDA’s Warning Letter (WL) by properly addressing each of the observations and ensuring that the company would be in full FDA compliance to the QSR/cGMPs by the time of next FDA inspection.

We gave the FDA a timeframe for bringing the operations into compliance and kept the FDA continuously informed on the progress of the corrective actions.

Once we reached a point of where we felt the company was in full compliance and ready for a reinspection, we notified the FDA. They didn’t let us know when they were going to reinspect the facilities or that they were planning to inspect all three plants at the same time.

Well, a few weeks later, the FDA sent out three sets of two investigators each. They visited all three company plants on the same day, starting on a Monday.

Luckily, we, as consultants, were able to attend all three inspections to monitor what was going on. Our main objective was to prevent and contain any possible problems with the inspections so that they would not escalate to major issues on the 483.

Even though we had things under control prior to the inspection and everyone was expecting the FDA visit, we were still surprised at the multi-site attack all at once. A little bit like D-Day.

The FDA inspection lasted three days at each site.

Our preparation paid off, and the three inspections went really well in addressing FDA’s concerns. In the end, we received only four inspectional observations between the three facilities.

Later I had the chance to speak with the FDA compliance officer who was handling this case, and with whom I had developed a relationship. He explained that he was shocked at the inspections outcome as he was not expecting to find the company in compliance. He told me that a prepared “injunction” was waiting on his desk for his signature, since FDA was convinced that the inspections would still show major problems. These three inspections were the last final review prior to the issuance of the injunction, which would basically close the company down and requiring them to sign a “consent decree” if they wanted to restart the operations.

That was avoided because the company understood what was necessary to bring the operations into compliance. They followed all our instructions and were well prepared for the FDA visit.

Well, we recently came upon a similar situation with a company called iRhythm Technologies that manufactures a heart arrhythmia monitoring device called the Zio.

The company’s first FDA inspection was in July/August 2022 with an FDA-483 issued at the conclusion of the inspection on Aug 12.

It was a pretty substantial FDA-483 and showed some serious issues. This inspection found problems with the company’s labeling claims, software changes without a 510(k) submission, QSR/cGMP deficiencies, and other issues.

FDA initially cleared the Zio device for capturing, analyzing, and reporting symptomatic and asymptomatic cardiac events for long-term monitoring. However, iRhythm marketing materials promoted their Zio device for near real-time monitoring as a mobile cardiac telemetry monitor that can provide notifications immediately to high-risk patients.

FDA was very concerned with these claims as the high-risk patient group was never approved under the Zio 510(k) clearance. These types of patients are more likely to suffer life-threatening arrhythmias and, therefore, require real-time monitoring (which Zio device does not offer) for possible clinical intervention.

These multiple issues resulted in a warning letter being issued nine months later, on May 25, 2023. Usually, FDA can issue warning letters within three to four months after a violative inspection if the initial FDA-483 does not include device labeling or claims issues. The labeling and claim related found during an inspection have to be reviewed by FDA’s Washington, DC, area office prior to the issuance of a warning letter. That is the reason the iRhythm warning letter took so long to be posted after the inspection.

We could not review the company’s responses to the 483s or the warning letter to evaluate the quality of their corrective actions. However, we do know that on July 15, 2024, the FDA decided to visit the company again. On the same day, both company facilities — one in San Francisco, CA, and another in Orange County, CA — received highly experienced FDA investigators who conducted compliance inspections.

The inspections resulted in additional 483 observations focused on the regulatory compliance, including complaint handling, medical device reporting, and risk analysis regarding the company’s certified technicians’ ECG reports in the CAPA process.

While we have yet to see how iRhythm plans to remediate their latest FDA situation, the company’s CFO already announced his departure from iRhythm effective Aug. 31.

All regulated companies should take notice of the standard warning the FDA includes in their letters: “Your firm should take prompt action to address any violations identified in this letter. Failure to adequately address this matter may result in regulatory action being initiated by the FDA without further notice. These actions include, but are not limited to, seizure, injunction, and civil money penalties.”

If your company has multiple facilities that are subject to FDA inspection, keep in mind that systemic deficiencies at all or either one of these locations can jeopardize the compliance of the entire company.

The outcome of these follow-up inspections is yet to be seen. But FDA does not usually take such critical actions as dual or follow-up inspections unless they intend to take such action.

This guest blog was written by Alan Schwartz, President of mdi Consultants, Inc. He has 52 years of FDA regulatory experience. He started out as a field investigator for the U.S. FDA and moved up to supervisor of field operations. In 1978, he resigned from FDA and founded mdi Consultants, Inc., an FDA regulatory consulting company. mdi assists medical device manufacturers to understand and comply with the FDA regulations (21CFR 820, QSR/cGMPs) as well as FDA regulatory strategies and all types of device submissions. For more information, e-mail This email address is being protected from spambots. You need JavaScript enabled to view it. and reference “Dual Inspections” or visit https://mdiconsultants.com. 

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