FDA finalizes guidance extending inspection authority to medical devices

Regulatory Background: Facility inspections, FDASIA and FDARA

• In 2012, the FDA Safety and Innovation Act ( FDASIA) gave the FDA new authority. Specifically, it authorized the FDA for the first time to take regulatory actions against firms that delayed, denied, limited or refused an inspection. Section 707 of FDASIA – now contained in the U.S. Code at Section 704(a) – states that the FDA can determine that a drug is adulterated if it “has been manufactured, processed, packed, or held in any factory, warehouse, or establishment and the owner, operator, or agent of such factory, warehouse, or establishment delays, denies, or limits an inspection, or refuses to permit entry or inspection” (emphasis added).
• The intent of the legislation was to prevent companies from stonewalling the FDA’s inspectors, especially at international facilities where the FDA typically has less power to compel entry. Companies had previously been accused of taking actions to limit investigator access to a facility (especially in cases of unannounced inspections), not permitting access to specific records, delaying access to facilities or records, or other actions that seemed to be in bad faith.
• Under the new approach outlined in FDASIA, the FDA was given a powerful bargaining tool: Either grant the FDA access to a facility and the documents therein, or you won’t be permitted to market your product since it will be technically adulterated.
• Following the passage of the FDASIA legislation, the FDA released a guidance document on the subject. In 2014, the FDA released a final guidance document, Circumstances that Constitute Delaying, Denying, Limiting or Refusing a Drug Inspection. The guidance is mostly a list of the specific examples that might cause a company to be in violation of Section 704(a). For example, the FDA said it would consider a facility that “will not agree to a proposed inspection start date and does not give a reasonable explanation for its failure to do so” to be delaying the inspection. It would similarly view actions that seek to reschedule an inspection “without providing a reasonable explanation,” or failure to respond to the facility’s designated contacts.
• In 2017, the FDA gained an expanded version of its inspection authority meant to expand this approach to medical devices. Under the FDA Reauthorization Act (FDARA) of 2017, FDA could now deem medical devices adulterated based on the delay, denial or limitation of an FDA inspection, or refusing entry or inspection, just as it can for drugs.

The FDA has now finalized the guidance on “delaying, denying, limiting, or refusing” inspections

• A revised draft version of the 2014 guidance had been issued in October 2022. As AgencyIQ described at the time, the agency’s drafted changes to the 2014 version of the guidance on delaying, denying, limiting or refusing inspections focused on expanding the existing content to medical devices – adding in “and device” and a device-related example of the guidance. The examples given in the guidance are specific situations or activities that the agency would consider to be in violation of 704(a), and therefore give the agency grounds to declare the product manufactured in a facility to be adulterated.
• The final guidance doesn’t change much compared to the 2022 draft guidance – or the 2014 guidance. The final guidance generally finalizes the changes as drafted, adding the phrase “and device” to several sections of the guidance and adding in new language specifically citing the FDA’s authority related to device inspections. This includes references to the requirement that FDA pre-announce certain device inspections, which is currently not a requirement for drug inspections.
• There are a few additional wording changes, such as updating the phrase “proposed inspection start date” to “announced inspection start date” (emphasis added) and clarifying that certain “potentially reasonable explanations” that might result in drugs being adulterated relate only to scheduling delays, not the actual delay of an inspection itself.
• Some new examples of when delays would/would not be acceptable: Per the new final guidance, a potentially reasonable explanation leading to a delay in a device inspection could be when the device facility “does not provide the FDA investigator access to environmentally controlled areas until the investigator accommodates the facility’s precautionary measures to prevent contamination and risk of personal safety” – similar to the already-established example of a facility asking an FDA investigator to comply with their documented gowning procedures. An unreasonable explanation (that might lead to a product being deemed adulterated) could be a facility not having the “necessary facility personnel” available on a pre-agreed-to inspection date, or the manufacturing site not operating on the day of the inspection.
• Delays in accessing records: The agency added some additional clarifications of situations that are “potentially reasonable” and could cause a delay to accessing records, including if accessing records during an inspection when they are being used for the in-progress operations and would disrupt the operation – so long as those records “are provided as soon as practicable,” or if the records “are stored off-site and require reasonable additional time to collect.” The reasonable duration for such a wait, the agency now states, should be “agreed upon by the facility and FDA.”
• A few new examples in “limiting” inspections, including limiting access to the facility or manufacturing process, limiting access to records, collection of samples, or photography. The agency has added a few new examples of what would be unacceptable (and therefore could lead to a determination that a product is adulterated), such as interrupting operations in order to prevent the investigator from observing them, removing sections of records (e.g., removing data columns in excel, exporting only part of the electronic record that the FDA is asking for, or locking a spreadsheet), or simply not providing electronic copies of records. The new final guidance does now include a situation that might be acceptable, however, in which a facility limits photography in circumstances in which “the facility can document that taking photographs of any raw material or assembly would adversely affect product quality.”

What’s next?

• In general, the policy remains the same. The agency has added some new language specific to the device authority, and some new clarifying examples of what might or might not be unreasonable, but in general the policy on circumstances that delay, deny, limit or refuse an inspection remain in place and largely unchanged.
• It’s also worth noting that companies interested in understanding how FDA enforces this policy in practice should closely read FDA’s warning letters and Form FDA 483 inspection reports. The agency has referenced the policies under this guidance in several warning letters in recent years, often articulating the exact sequence of events that have led to adverse findings. Or, as in the case of this inspection report, instances where the company appeared to be sneakily trying to delay the inspection in a way that would allow them to destroy specific records.
• This is a new clarification of the policy for device manufacturers, even as the agency has had authority to deem products adulterated for delaying, denying, limiting or refusing access to inspectoral staff for nearly seven years.

Featuring prior research from Alexander Gaffney
To contact the author of this item, please email Laura DiAngelo ( ldiangelo@agencyiq.com).
To contact the editor of this item, please email Alexander Gaffney ( agaffney@agencyiq.com)

Key Documents and Dates

• Circumstances that Constitute Delaying, Denying, Limiting, or Refusing a Drug or Device Inspection