By Dan Goldstein
Most manufacturers of medical devices sold in the United States are inspected by the Food and Drug Administration. The frequency of inspections depends on device risk factors, as well as on new device submissions, previous violations, and FDA’s available resources. There are exemptions for low-risk (Class I) devices, as well as for participants in the international Medical Device Single Audit Program (MDSAP). But for everyone else, it’s wise to expect FDA’s knock on the door about every two years.
There are ways to prepare for that knock. First of all, FDA requires manufacturers to conduct their own internal audits. In addition, manufacturers who sell in most international markets receive audits by a Notified Body at least once a year. Between these internal and external audits, many quality defects are flagged and fixed before FDA shows up. However, FDA has its own unique regulations and inspection methods that most non-FDA auditors won’t cover.
Enter the mock FDA inspection. In this activity, a trained, independent auditor performs an inspection more or less according to FDA’s methods, but with supplements that help the manufacturer’s quality staff prepare for the real thing. The mock inspection does more than just find nonconformities that would otherwise have been found by FDA. Properly done, it also increases the quality staff’s understanding and ability to navigate the official inspection. This article describes ways in which the mock “investigator” (FDA’s term for an inspector) goes beyond FDA’s framework to add depth and value.
Providing color commentary
Mock FDA investigators should narrate the inspection as they work through it, not unlike a surgeon narrating a procedure as they perform it in a teaching hospital. The quality staff hosting the audit should be encouraged to record not only which documents are requested for inspection and the nonconformities found, but also the mock investigator’s narrated reasons: Why did I focus on this document? Why did I return to the warehouse to interview another employee? By understanding the mock investigator’s train of thought, the quality staff is less likely to be caught off guard during the official inspection. Questions that are anticipated can be more easily and accurately answered.
Similarly, the quality staff hosting the audit should be encouraged to ask their own questions: How to deal with ambiguous document requests? Which defects are likely to draw FDA’s attention? Employees providing documents from an unseen back room (or “war room”) can even come into the front room to ask the mock investigator which documents are best suited to the request at hand. In an official FDA inspection, manufacturers are often hesitant to ask the investigator anything, which can lead to misunderstandings and premature disclosures.
Modifying FDA’s methods
The mock investigator uses FDA’s Quality System Inspection Technique (QSIT), a modular method that’s structurally distinct from both FDA’s own regulations and the international equivalent, ISO 13485. However, although official FDA investigators follow QSIT fairly strictly, a mock investigator can choose to address some modules only briefly to focus on areas where trouble is expected.
For example, QSIT requires the FDA investigator to use FDA’s somewhat quirky, binomial method for determining sample sizes, which requires a bare minimum of 11 samples from any set under investigation (complaint records, CAPA records, etc.). Thus, the FDA investigator selects at least 11 sample complaints from the manufacturer’s complaint log, and then reviews all of them to verify that they comply with the manufacturer’s own complaint procedure. A mock investigator, after reviewing only six or seven complaints, might learn enough about the manufacturer’s complaint handling to skip the rest of the complaints, choosing instead to dig deeper into the manufacturer’s supplier management records.
Exceeding FDA’s standards
Typically, if two separate auditors examine the same quality system on consecutive weeks, each one will find their own set of nonconformities. After all, auditing is a series of subjective judgments: Which records to examine, how strictly to judge nonconformities, and so on.
Therefore, a skilled mock FDA investigator should strive to be more exacting than FDA itself in identifying “observations” (FDA’s term for nonconformities). By identifying more observations than an official FDA investigator would, the mock FDA investigator leaves a smaller gray area.
More color commentary, this time in writing
In the past 12 years, 43 percent of FDA’s medical device inspections have identified observations that the manufacturer must correct (https://datadashboard.fda.gov/ora/cd/inspections.htm, retrieved June 3, 2020). These are printed on Form 483, which is provided by the FDA investigator at the inspection closing meeting. Within 10 days, the investigator also creates an Establishment Inspection Report (EIR), which lists not only any observations, but also “discussion items.” These are questionable practices that do not rise (yet) to the level of an observation, such as, “Complaints are not processed in a uniform and timely manner.”
Here again, a mock FDA inspection can provide added value beyond FDA’s own methods. The mock investigator should create a unified report that covers not only the Form 483 observations and the EIR discussion items, but also the best strategies to address these issues to FDA’s satisfaction. And unlike Form 483 and the EIR, the mock investigator can revise their report to provide further details and advice, according to the manufacturer’s questions and comments.
Hosting a preparatory mock FDA inspection does not guarantee that the next official FDA inspection will be observation-free. However, if properly followed up by the manufacturer, the mock inspection does reduce the number and severity of future FDA observations. No less important, it gives the quality staff and top management the confidence they need to successfully navigate the challenge of hosting FDA on site.
About the author
Dan Goldstein is the associate director for quality assurance at MCRA LLC. His work on quality system and manufacturing requirements helps to keep devices and manufacturers in compliance with U.S. and international regulations and standards. A graduate of the University of Maryland University College, Goldstein has worked in medical device quality assurance since 2002 and for MCRA since 2016. He provides MCRA clients with FDA QSR and EU MDR gap assessments, mock FDA inspections, internal and supplier audits, manufacturing transfers, due diligence reporting, Form 483 remediations, medical device reporting, unique device identification, recall support, design history files, and technical documentation.