On July 12, 2013 the FDA released a Draft Guidance, Guidance for Industry Circumstances that Constitute Delaying, Denying, Limiting, or Refusing a Drug Inspection, for comment. The Draft Guidance was issued in support of the Food and Drug Administration Safety and Innovation Act (FDASIA). Under Section 707(b) of FDASIA, the FDA was required to issue guidance that defines the circumstances that would constitute delaying, denying, or limiting inspection, or refusing to permit entry or inspection, for purposes of section 501(j). This is because 501(j) adds a new twist to what is deemed an adulterated drug. Specifically, Section 707 of FDASIA adds 501(j) to the Food, Drug, and Cosmetic Act (FD&C Act) to deem adulterated a drug that “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.”
The draft guidance defines the types of actions, inaction, and circumstances that the FDA considers constituting delaying, denying, or limiting inspection, or refusing to permit entry or inspection. It presents a number of possible scenarios that illustrate situations where a manufacturer’s actions would be considered reasonable, as well as other cases where actions would lead to drugs at the facility to be considered misbranded or adulterated. Under the draft guidance, inspection delays that may cause drugs to be considered adulterated include, but are not limited to:
A facility that restricts an FDA investigator’s access to an area of the facility until a specific future date or time even though the area is operational; or
A facility that leaves an FDA investigator in a conference room without access to necessary documentation or responsible individuals for an unreasonable period of time that interferes with the investigator’s ability to complete the inspection.
Delays in providing the FDA with records or documents without a reasonable explanation may also be considered delaying an inspection.
Rejecting the FDA’s attempt to schedule an inspection, preventing access to certain areas of a manufacturing site or stopping an inspection from beginning are other common examples of behavior that may cause drugs to be considered adulterated.
Limiting the use of photographs, which the FDA considers “an integral part of an FDA inspection because they present an accurate picture of facility conditions” could also cause a facility’s drugs to be considered adulterated. The FDA noted that t photographs have been used to documented poor conditions, such as “evidence of rodents or insect infestation; faulty construction or maintenance of equipment or facilities; product storage conditions; product labels and labeling; and visible contamination of raw materials or finished products.”
The comment period ending on September 13, 2013. In commenting, industry groups and manufacturers cited as the greatest concern or complaint that the draft guidance lacked clarity on circumstances where a manufacturer’s actions would be used by the FDA against it.
One commenter stated that it would be “very helpful to have further guidance on what would be considered a ‘reasonable explanation’” for delaying an inspection. While another commenter went on to say “it is not clear exactly what the FDA would deem to be a ‘reasonable explanation’ or ‘adequate justification.’ These terms need to be better defined and FDA should provide detailedexamples and explanations.” And, also adding that it “leaves it too much to the opinion of any particular FDA investigator that the inspection process is being hindered,..”
Other concerns and comments raised centered on circumstances when an FDA investigator is left in a conference room without access to necessary documentation or responsible individuals for “an unreasonable period of time,” which under the guidance is cited as a cause for deeming a manufacturer’s products misbranded or adulterated. One comment noting that such language used in the guidance “seems to assume malicious intent to avoid providing records, and there is an underlying assumption that the record(s) requested actually exists.” And furthermore, “that reference could be open to a wide range of interpretations depending on the inspector(s) involved and their style of conducting inspections. What is an unreasonable period of time?”
The biopharma industry trade group BIO took particular concerns with how manufacturers will be notified of inspections. In its comment to the FDA, saying that it is “concerned that under the Draft Guidance an inspector would have the authority to characterize a delay or a limitation as sufficient to adulterate a drug without providing the Sponsor sufficient notice or due process.”
The FDA is reviewing comments received.