The Food and Drug Administration (FDA) recently issued a notice announcing the Agency’s revised guidance for industry defining the types of action, inaction, and circumstances that FDA considers to constitute delaying, denying, or limiting inspection, or refusing to permit entry or inspection for the purposes of making a drug adulterated. The revised guidance, entitled “Circumstances that Constitute Delaying, Denying, Limiting, or Refusing a Drug Inspection,” follows the enactment of the 2012 Food and Drug Administration Safety and Innovation Act (FDASIA), which added a provision (and teeth) to the Food, Drug, and Cosmetic Act (the FD&C Act) concerning inspections that render a drug “adulterated” – a new term used by the FDA in this context. Specifically, a drug adulterated under FDASIA “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.” FDA issued the revised guidance in response to comments on the Agency’s draft guidance for industry of the same title issued in July 2013.

The revised guidance clarifies FDA’s expectations regarding the types of action, inaction, and circumstances that make a drug adulterated under FDASIA and the FD&C Act. FDA also provides examples that constitute reasonable explanations for actions, inactions, or circumstances that could otherwise be considered delaying, denying or limiting inspection, or refusing to permit entry or inspection, as discussed below.

Delays of Inspections: While the guidance acknowledges that delays may occur for many reasons – some of which are beyond the control of the facility – it explicitly states that where an owner, operator or agent causes the delay of an inspection, this may cause the drugs to be deemed adulterated. FDA provides examples of delaying a pre-announced inspection that include, but are not limited to:

  • A facility will not agree to a proposed inspection start date and does not give a reasonable explanation for its failure to do so
  • A facility, after scheduling an inspection, requests a later start date without giving a reasonable explanation
  • A facility fails to respond following the FDA’s attempt to contact the facility’s designated contact(s)

Delay During an Inspection: The guidance suggests that actions by a facility’s owner, operator, or agency before or after the beginning of an inspection, that impede an FDA investigator at the inspection site from performing the inspection in a reasonable manner, may be considered delaying the inspection. However, FDA notes that it will recognize minor delays from good faith efforts by the facility to comply with FDA requests as not unreasonable. FDA provides examples of delays during an inspection that may cause drugs to be adulterated:

  • A facility does not allow the FDA investigator access to an area of the facility until a specific future date or time, even though the area is operational and is an area of the inspection site that FDA has authority to inspect, without giving a reasonable explanation
  • A facility leaves the FDA investigator in a conference room without access to necessary documentation or responsible individual for an unreasonable period of time that interferes with the investigator’s ability to complete the inspection

Delays in Producing Records: FDA emphasizes the importance of the Agency’s preparation for inspecting drug facilities in collecting and reviewing hardcopy and electronic records, files and papers. The guidance offers examples of delays in producing records that may cause drugs to be deemed adulterated that include, but are not limited to:

  • The FDA investigator, during an inspection, requests, within a specific, reasonable timeframe, records that it has authority to inspect, but the facility fails to produce the requested records within the timeframe requested by the Agency, without reasonable explanation
  • The FDA requests records under its legal authority to do so, but the facility fails to produce the requested records in a timely manner, without reasonable explanation

FDA emphasizes that in instances where the facility provides a reasonable explanation for delaying production of records, the facility should also ensure that the resulting delay is of a reasonable duration.

Limiting of Inspection: The guidance explains four circumstances where an owner, operator, or agent of a drug facility prevents an authorized FDA representative from conducting an inspection that constitutes a limitation that may cause drugs to be deemed adulterated:

  • Limiting access to facilities and/or manufacturing processes
  • Limiting photography
  • Limiting access to or copying of records
  • Limiting or preventing collection of samples

While the guidance suggests that impeding or resisting photography by an FDA investigator may be considered a limitation if such photographs are determined by the investigator to be necessary to effectively conduct that particular inspection, there is no mention of the Agency’s authority to regulate this activity in MAPPs, FDA’s internal guidelines.

Refusal to Permit Entry or Denials of Inspection: FDA interprets the term “refuses to permit entry or inspection” to include not only active, but also passive behavior and non-action by the owner, operator or agent of a drug facility, to prevent an authorized representative of the FDA from conducting an inspection, or to prevent the FDA from completing an inspection. Denials of inspection also include statements or physical actions intended to avoid inspection, or to mislead, deceive or impede the investigator. FDA provides examples that may constitute denying an inspection that may cause drugs to be adulterated:

  • A facility ignores or rejects the FDA’s attempt to schedule a pre-announced inspection
  • The facility does not allow the FDA investigator, upon arrival at the facility, to enter the facility or begin the inspection
  • A facility does not allow the FDA investigator to inspect the facility because certain staff members are not present, without a reasonable explanation, or
  • A facility sends staff home for the day and tells the FDA investigator that the facility is not producing any product

Although neither the FDA’s revised guidance nor the FD&C Act specifically define “reasonable,” FDA has long maintained that the inspectional authority under section 704 of the Act “extends to what is reasonably necessary to achieve the objective of the inspection.” Further, FDA contends that it will consider reasonable explanations for behavior that may otherwise be considered to be delaying, denying, limiting, or refusing an inspection under the revised guidance. The guidance’s vagueness reinforces the importance of taking the following key steps to ensure FDA inspection compliance:

  • Review FDA rules and guidance on how to conduct a good inspection
  • Assess facility’s existing plans for FDA inspection
  • Develop written internal procedures and systems that specifically address inspectional issues
  • Consider rationale for any delays, limits, or denials of inspection
  • Train and prepare staff for FDA inspections, including understanding the company’s positions and employees’ roles before, during, and after FDA investigations
  • Track what is stored at the facility and what is provided to the authorized FDA representative at inspection