Late last month, the FDA finalized a new guidance document, explaining the agency's current thinking on the circumstances that may arise in connection with an establishment inspection that it would consider to impose an inappropriate limitation on its inspection authority. The Food and Drug Administration Safety and Innovation Act (FDASIA) deems a drug or medical device adulterated if it has been manufactured processed, packed, or held in any factory, warehouse, or establishment that delays, denies, or limits an inspection, or refuses to permit entry or inspection.
The guidance applies to all facilities that are subject to inspection under section 704 of the Food Drug & Cosmetic Act, including both drugs and medical devices.
Among other agency actions, a firm may be subject to a Warning Letter, if there is a delay, denial or limit to FDA's inspection by the facility's personnel. Until FDA is able to inspect the facility, FDA also may withhold approvals of new applications and supplements and may refuse product entry into the United States if the subject facility is outside of the country.
The finalized guidance provides newly added examples of what it considers to be "reasonable explanations" for delays, denials and limitations on inspections. These examples provide some clarity for manufacturers on how to respond to a surprise FDA inspection if an inspector comes knocking.
For example, a reasonable explanation to delay an inspection would be if manufacturing takes place one day a month, and an inspection would be more fruitful if the manufacturing site was active. In addition, if there are minor delays resulting from good faith efforts to comply with FDA requests, FDA will usually not consider this unreasonable.
The guidance indicates a reasonable explanation for not allowing an FDA inspector access to all areas in a facility would be that he/she would first need to comply with "gowning up" requirements to enter a controlled area. Providing an inspector with policies detailing such requirements upon initiation of the inspection would be helpful in providing support for this point if a disagreement were to arise.
Other examples of reasonable explanations for delays identified by FDA in the guidance relate to the availability of requested documentation. A delay in the production of records may be excused if translations are required, the records are currently being used in production or the volume of requested documents is too large to be printed in time.
FDA asserts that it has always been permissible for inspectors to take photographs as part of inspections to capture the state of a facility. The guidance describes a narrow exception when it may be reasonable to prohibit an FDA inspector from taking photographs if such activity would adversely impact the product or its chemical characteristics. Having clear procedures and scientific justifications in place regarding the adverse impact of photography on product quality (i.e., the impact of the flash of a camera on product integrity) will assist manufacturers in providing support if they choose to limit photography in a designated area.
The guidance further emphasizes that refusing to permit entry of an inspector includes not only active, but passive behavior, such as not unlocking certain areas or avoiding other necessary action that would permit access to an investigator. However, the examples provided in the guidance are quite limited. The term "passive" is vague and thus could be interpreted in a variety of ways. Thus, ensuring quick access to areas FDA has authority to inspect is critical.
It is paramount that drug and medical device manufacturers act swiftly in all matters when an FDA inspector arrives at the door. Timing and communication with the inspector are key in ensuring that the inspector is aware of good faith efforts taking place to comply with all requests. Companies should ensure that responsible personnel and their associated back-ups are designated should the need arise to respond to an FDA inspector. Keeping these steps in mind will avoid the adverse consequences of being found to have hindered an inspection.