On October 21, 2014, FDA announced the availability of its Final Guidance for Industry, Circumstances that Constitute Delaying, Denying, Limiting, or Refusing a Drug Inspection (here). This document finalizes Guidance that was published in draft for comment on July 12, 2013. The Guidance is intended to fulfill FDA’s obligation in the 2012 Food and Drug Administration Safety and Innovation Act (FDASIA) to define the circumstances that would constitute delaying, denying, or limiting inspection, or refusing to permit inspection, actions that FDASIA established as causing drugs to be adulterated.
Following publication of the 2013 Draft Guidance, FDA received twelve comments, including eight from industry groups and the rest from companies or individuals. Most comments addressed in one way or another the lack of clarity in the draft about the word “reasonable”. The Final Guidance retains examples from the 2013 draft describing situations that FDA considers to constitute unreasonable delay, denying, limiting and refusal. However, in the Final Guidance, FDA incorporated a number of changes to add clarification around the concept of reasonableness. The clarifying additions include examples of situations resulting in delay, denial or limitation that FDA would not consider unreasonable, and would therefore not cause FDA to deem the products adulterated. Some of the clarifying examples were drawn from the comments.
One such example of a reasonable delay describes a situation in which a facility runs only one manufacturing campaign per month, and requests a different inspection date so that manufacturing will occur during the inspection. Other examples where delay would not be considered unreasonable:
- Access to an aseptic processing area is not provided to the FDA investigator until the investigator accommodates the facility’s gowning procedure.
- Translation of records from the local language into English is not readily available.
- Records are not available for the investigator because they are being used for a manufacturing operation in progress.
- The volume of records requested by the investigator requires a reasonable time to compile.
- Appropriate personnel to accurately answer questions are not immediately available at the beginning of an unannounced inspection.
- The FDA investigator arrives for an unannounced inspection, but the facility is closed due to scheduled maintenance.
- OSHA training is required for entrance into particular areas.
- Taking photographs would adversely affect product quality, due to chemical properties of the product. (Some comments requested limits on photography for other reasons such as protection of intellectual property, but these were predictably ignored.)
The Final Guidance states, “FDA intends to work with facilities to conduct inspections and procure the information necessary to achieve the objective of the inspection. FDA will consider reasonable explanations for behavior that may otherwise be considered to be delaying, denying, limiting, or refusing an inspection.” The changes to the Final Guidance have been made in that spirit. However, the Guidance does not incorporate what some comments requested- namely a negotiation, appeal, or escalation process to work out differences between the investigator’s expectations and the firm’s ability to comply.
Violations of the FDASIA requirements regarding delay, denying, limiting or refusal are being cited in Warning Letters, and companies must understand their obligations under FDASIA and the Final Guidance in order to avoid regulatory action. Be alert for any concerns on the investigator’s part, and it may be warranted to ask periodically during inspections if the investigator believes there has been any such violation, so that the inspection process can be adjusted if necessary.
Hyman, Phelps and McNamara have a different twist on the potential impact of this Guidance (here). Please contact Fran Zipp at email@example.com or Arlene Ocampo at firstname.lastname@example.org with questions regarding the new FDA Guidance .