Inspections, Compliance, Enforcement, and Criminal Investigations
Guide to Inspections of Medical Device Manufacturers
GUIDE TO INSPECTIONS OF
MEDICAL DEVICE MANUFACTURERS
GMP INSPECTIONAL STRATEGY
CP 7382.830 describes the inspectional strategy to be used. This Guide discusses how to perform a directed inspection, or a comprehensive inspection. It also discusses inspections of small manufacturers. In brief, all inspections of medical device manufacturers are to be directed inspections, with the exception of OAI follow-up inspections, which are to be comprehensive inspections.
Preannouncements, 483 Annotations, Post Inspectional Correspondence: ORA conducted a pilot program, Medical Device Industry Initiatives, in FY 96 through the first quarter of FY 97 which encompassed preannounced medical device inspections, annotated FDA 483s and post-inspectional correspondence for NAI and VAI inspections. The initiatives have been implemented on a permanent basis. The instructions for preannouncement, including the criteria to be used, 483 annotations and post-inspectional letters for NAI and VAI inspections are included as Attachment A to this guide.
One of the purposes to preannouncing is to assure that the appropriate records and personnel will be available during the inspection. Therefore, it is important you communicate to the firm the purpose of the inspection and a general idea of the records you may wish to review. If you find neither the appropriate personnel or records were available, please note this in your Establishment Inspection Report (EIR). This data may be used by the district in the future when considering whether this firm should be eligible for preannounced inspections.
With the finalization of the new Quality System/Good Manufacturing Practices (QS/GMP) regulation, FDA formally recognized a new systems approach to regulating medical devices. It is FDA's intention to use this same approach when conducting inspections. A systems level approach to conducting inspections means taking a broader view. A great deal of flexibility has been written into this regulation, which means Investigators need to more fully concentrate on the firm's state of compliance at the system level. How best can that be done?
It is important to focus the inspectional effort on those systems that will provide the firm with information regarding failures in their process, the actual device design, their raw materials, or their employee training. These systems include: complaints, MDRs, servicing, product acceptance, change control, process validation, design control, and internal audits. Problems or failures in these areas are most likely to result in faulty or hazardous devices being released into commercial distribution. These areas may also serve as first indicators for the firm that nonconforming product may have been distributed. Therefore, a firm's system for recognizing failures and implementing corrective and preventive actions is also a key system to assure a firm meets its own and FDA's requirements for quality medical device design and manufacturing.
Because of this, FDA uses a directed inspection approach for all surveillance and pre-approval inspections. Generally, more comprehensive inspections are done only after a firm has been found to not be in substantial compliance based on a directed inspection, i.e. a follow-up inspection of an OAI (Official Action Indicated) inspection.
The purpose of a directed inspection is to look at those areas that are of the greatest concern in assuring that a firm is not designing, manufacturing or distributing hazardous or non-conforming devices. These systems should be inspected to assure that they conform to the QS/GMP requirements. The information contained in these systems may also indicate there are problems in designing, manufacturing, servicing, training, testing, labeling, packaging, etc. They may indicate that hazardous or nonconforming devices have been manufactured and/or distributed. This type of information should be used to help focus the inspection on a particular device, lots or batches of devices, or on particular manufacturing processes.
As a general rule, the Investigator should select devices for inspectional coverage which, because of what they are made of or how they are made, have the highest potential for problems that could result in the design, manufacture and/or distribution of unsafe or unreliable devices. This rule should be applied when there is no evidence in the complaint, MDR, testing or servicing records of specific problem devices. If there are recall or MDR issues already known regarding a particular device, or a device manufactured by the firm has been the subject of prior warning of non-compliance, then these devices should be the focus of your inspection. Once a device has been selected, the inspection should focus on those significant systems that are meant to assure the manufacture of safe and reliable devices: process validation, component acceptance, change control, design control, and control of nonconforming product.
Evidence of nonconforming products should be viewed as an indicator of noncompliance with the QS/GMP. As an inspectional function, this is the best starting point to inspect the overall quality system. For example, if the firm does not have the documents and data related to our reports of non-conforming devices or of devices that caused injury or death (MDR) this would be a significant non-compliance with the QS/GMP.
Inspectional observations should focus on cause and effect to link observed problems to the potential of manufacturing nonconforming product(s). Start with the evidence that an unsafe and/or unreliable product was or may have been distributed as indicated in MDRs, complaint records, service records, incomplete corrective and preventive actions, and distribution records for release of nonconforming products. The inspection should then be focused on those QS/GMP systems that have a high probability of causing the problems indicated by the complaints, MDRs, etc.
Inspectional observations relative to those systems should be related to noncompliances of significant risk. It should also be determined whether other devices with these potential problems would result in the distribution of an unsafe or unreliable product.
Any observed nonconformance to written procedures should be documented with a copy of the written procedure and additional observations to show the nonconformance is not just a one time occurrence. If observations are related to people dependant processes, the inspection should provide sufficient documentation to show the problem to be a training issue, the use of unqualified people or process validation related problems.
Lastly, the QS/GMP places major emphasis on the role of management and management responsibility. The inspection process should show through the firm’s written documentation the role of management in the quality process to prevent the design, manufacture and distribution of nonconforming products.