When medical devices are cleared/approved for sale in U.S., manufacturers are informed that they are expected to comply with all applicable U.S. medical device requirements, including quality system requirements. Inspections of foreign establishments pose unique challenges to FDA—both in human resources and logistics. While FDA publishes its inspection guidelines, it does not make available to the public its inspection program indicating which medical device establishments it will inspect. FDA does not routinely inspect manufacturers of Class I devices(1) , although it may inspect when there are areas of concern. U.S. FDA currently lacks adequate resources to inspect more than a small percentage of foreign manufacturers of Class II and Class III devices each year; however, it is adding more capability for inspections, as it recognizes the need to perform more inspections. As a result of past lack of resources, some foreign manufacturers have marketed their devices in the United States for many years without having been inspected by U.S. FDA and in some cases without ensuring compliance with the U.S. Quality System Regulation (21 CFR Part 820). Some of these manufacturers believe that conformity to the voluntary standard ISO 13485, Medical devices— Quality Management Systems (QMS)—Requirements for regulatory purposes, will be sufficient to successfully pass a U.S. FDA facility inspection. They may also believe that ISO quality system certification and surveillance audits are sufficient enough to prepare for FDA inspection.
These assumptions are generally incorrect. A foreign manufacturer may have been marketing its devices in the United States for some time without U.S. FDA inspection, and therefore may not have an adequately designed quality system under the U.S. FDA Quality System Regulation (QSR). Thus, in a first U.S. FDA inspection, the manufacturer may be surprised by the number of noncompliance areas cited. It may also be that the manufacturer has not recognized that U.S. FDA inspectors and ISO quality system auditors have differing priorities in their inspections/assessments.
FDA generally notifies manufacturers about a week in advance of post market quality system inspections of domestic establishments and perhaps 2-4 weeks in advance for foreign establishments.
Preparing for a U.S. FDA inspection should be an organized activity involving all company personnel performing work covered by the QSR, including executive (top) management, design and development, production, quality control, quality assurance, warehouse, purchasing, human resources, packaging, distribution, information technology and perhaps, others.
These are some of the topics that companies should consider covering during such a preparation:
It is important to note that materials that can be used to develop such an inspection preparation program are readily available from many sources, including online, most notably from the U.S. FDA website (www.fda.gov).
Manufacturers should avoid the misconception that U.S. FDA inspections consist only of an assessment of QSR compliance. Inspections also examine compliance with the following regulations:
In addition, Electronic Records and Signatures (21 CFR Part 11) may be evaluated, as well as Electronic Products compliance (21 CFR 1020, et. Seq.).
Incidents in which a device may have caused or contributed to a death or serious injury must to be reported to FDA under the Medical Device Reporting program. Some manufacturers fail to develop procedures to ensure that MDR requirements are met because they assume that the U.S. importer alone is responsible for U.S. adverse event reporting.8 This is incorrect as “all manufacturers of finished medical devices and components which are ready for use, including foreign manufacturers, are now subject to the requirements of the MDR regulation, despite registration status”.
A similar error is sometimes made regarding compliance with corrections and removals. Although the manufacturer or the U.S. importer can submit corrections or removals reports to U.S. FDA, the manufacturer needs to ensure that proper procedures have been implemented to comply with these and other U.S. importer requirements. Failure to do so could jeopardize the regulatory compliance status of the device and, in serious cases, the continued import of the devices into the United States. Reports of corrections and removals are required for class I and class II recalls. Under 21 CFR 806, manufacturers and importers need not report events categorized as class III recalls under 21 CFR §7; only record keeping requirements would apply.
Manufacturers should always ensure that their establishment registration and device listings are current. The manufacturer of a tracked device also should ensure that U.S. importers and distributors are fulfilling the requirements in 21 CFR Part 821, because failure to comply with tracking requirements may cause the device to be detained at the U.S. point of entry. The firm should update the listings and verify that their listings are up-to-date every six months and update them if they are not. The firm should renew its annual registration as required by 21 CFR Part 807.
Preparing for an impending FDA inspection requires a well-organized program, and is vital to a successful outcome. One excellent way to achieve preparation is to engage independent parties to perform a “mock audit” which will give the organization experience in reacting to an FDA-like audit. Knowing what to expect can save hours of anxiety.
UL can provide training using the same content used for training FDA Inspectors, conduct the pre inspection or gap assessment audit to help the manufacturer to prepare for the actual audit and provide on-site support during an FDA inspection.
Many valuable lessons will be learned in how to prepare for and manage an inspection by FDA, ensuring manufacturer/ company reduces the potential for the issuance of damaging FDA Form 483s and associated Warning Letters that can seriously disrupt business and profitability.