By Peter Ohanian, Halloran Consulting Group
If you are a manufacturer or a processor of FDA-regulated products, sooner or later, you can expect a visit from FDA. The purpose of this visit is to verify compliance with all relevant regulations — most commonly referred to as an “FDA inspection.” But not all inspections are created equal.
FDA performs four different types of inspections at many different types of facilities, and your company’s response should be tailored to the specific type of event. Facilities that fall under FDA’s watchful eye include:
FDA’s inspection authority also extends to foreign manufacturing and processing sites for FDA-regulated products sold in the United States. Fall within these bounds, and you can anticipate an FDA inspection at your facility. For the scope of this article, though, we will focus specifically on the inspection of medical device manufacturers.
The four different types of inspections conducted by FDA are pre-approval inspection, routine inspection, compliance follow-up inspection, and “for cause” inspection. Each is intended to help protect the public from unsafe products, but the focus and expectations of each type of inspection are different.
Pre-Approval Inspections are conducted after a company submits an application to FDA to market a new product. These inspections focus on verifying data included in the application, and confirming that the facility is capable of manufacturing said product. The outcome of a pre-approval inspection is that inspectors will recommend for or against FDA approval.
Routine Inspections are mandated by law every 2 years for class II and class III device manufacturers. They follow a prescribed method known as Quality System Inspection Technique (QSIT), which will be discussed later in the article. If a serious public health risk is identified during a routine inspection, the inspection type may then switch to a “for cause” inspection.
Compliance Follow-Up Inspections review actions taken by a firm/manufacturer in response to a previous inspection that resulted in significant 483 observations or a Warning Letter. A compliance follow-up is conducted to verify the adequate correction of previous violations, to document continuing violations, or to support future regulatory action.
“For Cause” Inspections investigate a specific problem that has been reported to FDA. The source of the report can be the manufacturer (e.g., resultant of a recall, MDR), consumer/user complaints, or even a disgruntled employee. A “for cause” inspection will focus on the particular issue, but can branch out to cover unrelated elements of the firm’s operations. This inspection usually is initiated at the request of CDRH, ORA, or regional directive. These inspections typically are more in-depth than routine inspections, and they may not follow a QSIT approach.
Preparing For Inspections
Will you know when FDA is coming? It depends. Pre-approval and routine inspections typically are announced five calendar days in advance. Firms with a history of violative inspections will not be granted this luxury, and FDA may show up unannounced. Compliance follow-up inspections and “for cause” inspections are not pre-announced. FDA inspection of a foreign establishment typically is preannounced two to three months in advance to allow time for travel and scheduling logistics.
Ever wonder how FDA chooses which firms should be selected for a routine inspection? FDA uses a risk-based approach. Using the Establishment Registration database, FDA identifies who manufactures which devices. The Device Listing database is used to identify which devices each firm distributes. The firms then are prioritized by risk: Class III > Class II > Class I. Consideration also is given to firms manufacturing high-risk products, like implantable devices or life supporting/life sustaining devices. Firms that have recently introduced a new device to the market also are given higher priority, as well as those that have had significant prior violations and complaints.
The majority of inspections are routine inspections. FDA developed QSIT as a means to systematically assess the compliance of a firm. It’s worth noting that, while FDA has developed QSIT for medical device manufacturer inspections, they’ve also developed BIMO for drug manufacturers.
QSIT identifies the four major subsystems of the quality system: Management Controls, Design Controls, Corrective and Preventive Actions (CAPA), and Production and Process Controls. It evaluates and describes the purpose and importance of each subsystem, providing flowcharts and inspectional objectives for each subsystem. There are two types of QSIT inspections: Level I Abbreviated and Level 2 Baseline.
A Level 2 Baseline QSIT inspection is a comprehensive inspection covering all four major subsystems. It is conducted when a firm has never had a Level 2 inspection, and every six years thereafter. It provides an overall evaluation of the quality system.
A Level 1 Abbreviated QSIT inspection is conducted after a firm has had a Level 2 inspection, and the quality system was found to be in compliance with all requirements. A Level 1 inspection always includes the CAPA subsystem, plus one other major subsystem. A different subsystem will be chosen for each subsequent Level 1 inspection.
FDA’s Guide to Inspections of Quality Systems describes the process in greater detail.
Regardless of the type of inspection, it is up to you to always be prepared for FDA to visit your facility. Understanding the types of inspections and possible inspection locations is just the first step. Make sure to sit down with your team and formulate a concrete plan for inspection readiness. Have a procedure available so employees know what to do and how to conduct themselves when an FDA investigator arrives at your facility. Finally, it’s always best practice to ensure your quality system documentation is available and up-to date.
If you have earned a follow-up or a “for cause” inspection, make sure you take purposeful, effective, and documented steps to respond to and correct previous mistakes or oversights. When FDA returns, it is not enough to say you have a plan; you will have to prove you’ve solved the initial issues. As always, an ounce of preparedness is worth a pound of remediation. Use your new understanding of types of facility inspections as motivation to kick-start preparation for your company’s inevitable next inspection.
About The Author
Peter Ohanian joined Halloran Consulting Group in 2015. He has more than 35 years of industry experience in medical device quality assurance and regulatory affairs. He has an extensive background establishing compliance programs and developing product clearance strategies.
Prior to joining Halloran, Peter was the Vice President of Quality and Regulatory Affairs for Philips Healthcare, providing leadership and strategic direction for their patient monitoring and clinical informatics business. Peter also held similar roles with ZOLL Medical Corporation and Visualization Technology Corporation and has served on the Board of Directors for MassMedic.
Peter earned a bachelor’s degree in biology from Boston College and a master’s in engineering management from Northeastern University. He also is Regulatory Affairs Certified by the Regulatory Affairs Professional Society.