The FDA oversees the safety of foods, medicines and medical devices. They can step in after a product is on the market if it’s not following laws (like when a company says their vaccine will help you get better faster, but it didn’t).
The FDA also inspects production facilities that make items regulated by them. This includes compounding pharmacies and companies that manufacture regulated products for import into the United States.
Routine Inspections
FDA routinely inspects drug and medical device manufacturers at their facilities to ensure they are following current good manufacturing practice (CGMP) regulations. CGMP inspections are typically done annually. FDA does this in cooperation with international regulators, as it is critical to ensure safe, effective and high-quality products are available for patients in the United States.
During a CGMP inspection, the investigator will look at the four major subsystems of a firm’s quality management system: personnel, facility and equipment, materials and documentation/records/change controls. A firm with serious deficiencies found in more than one of these subsystems may be a risk to public health and could be subject to a for-cause inspection.
In addition, if serious deficiencies are observed at a contract sterilizer or contract manufacturer of finished devices, the FDA home program division(s) of the finished device manufacturers that use those services should schedule immediate follow-up inspections at those firms. FDA should also consider taking administrative/legal action against both the contractor and the finished device manufacturer if necessary.
During these follow-up inspections, the investigator will focus on issues resulting from the firm’s failure to correct significant deficiencies observed during previous inspections. These issues could include a failure to evaluate changes for new clearance (510(k) or approval (PMA), or signals with the product or across devices manufactured, such as recalls and consumer complaints.
Compliance Follow-Up Inspections
The FDA uses a risk-based approach to determine which medical device manufacturers it inspects. If the agency sees a lot of issues with a particular manufacturer, it will prioritize an inspection. This can include inspections based on 483 observations, warning letters and a variety of other factors. These inspections tend to be more focused and in-depth than a routine inspection. During these follow-up inspections, the FDA is looking to make sure any previous violations have been corrected.
During these types of inspections, the FDA will also be looking at the company’s quality management system, documentation, manufacturing processes and more. As such, it is important to have a strong quality control program in place. You should be documenting all of your processes and ensuring that any data is available quickly to the inspector.
When preparing for a follow-up inspection, it is often helpful to prepare a brief presentation that you can share with the investigator. This can help you to highlight any changes that have been made since the prior inspection and to provide an overview of the products and services your company provides.
In addition to preparing for the inspection, it is important to ensure that you have a good working relationship with your company’s regulatory team. Ideally, a manager or senior representative should accompany the inspector throughout the inspection to ensure that questions are being answered and that records are quickly retrieved.
Surveillance Inspections
The agency tries to keep up with inspections of medical devices, but the COVID-19 pandemic caused a big backlog. As of 2022, domestic and foreign routine inspections were down by about 79 percent compared with 2019. The agency has a lot to catch up on, which means the FDA may be showing up at your facility unexpectedly.
For these surprise inspections, you will not receive advance notice of the visit. They are often focused on any complaint or Form 483 observations noted during the previous inspection. In these cases, the FDA is trying to verify that the company has corrected the violations identified.
During these inspections, you can expect the inspectors to follow the Quality System Inspection Technique (QSIT) method. This involves examining four major subsystems of the quality system including: corrective and preventive actions, management controls, production controls, and design controls.
If you are manufacturing a Class II or Class III device, you should anticipate these inspections every two years. As a general rule, you will receive five days advance notice. However, like the pre-approval inspections, the FDA will use a risked approach when determining whether to inspect your company. This will look at factors such as your facilities history, the seriousness of the condition you’re treating, and the patient population your device aims to serve.
Pre-Approval Inspections
If you’re submitting a new medical device to the FDA, they will perform a pre-approval inspection before allowing your product on the market. During these inspections, the FDA will confirm the information submitted with your application to ensure that your manufacturing facility is suitable for producing the medical device. These inspections are typically more detailed than routine or follow-up inspections and can be more focused on specific issues. Generally, medical device manufacturers will receive 5 days of notice for this type of inspection (although foreign device manufactures may get 2-3 months or less).
If the FDA issues a warning letter or 483 observations during a routine, surveillance, or pre-approval inspection, they might want to revisit your facility to verify that you’ve taken the corrective actions necessary to address those concerns. During these compliance follow-up inspections, the FDA will evaluate whether your corrective action plan has been followed and that your quality system is functioning properly.
Regardless of the type of inspection, it’s important to prepare your facility for the FDA by assembling a cross-site team comprised of essential subject matter experts from development, analytical, tech transfer/tech operations, and manufacturing (including QC/Micro). This team should meet to review the CMC section of the NDA/BLA together and discuss the key reports that will be requested during the PAI. Assembling this team will ensure that your PAI goes as smoothly as possible and that you present a united front to the FDA inspectors.
