The U.S. Food and Drug Administration (FDA) recently published its final Guidance for Industry detailing circumstances that would constitute interference with a drug inspection under the Food and Drug Administration Safety and Innovation Act (FDASIA), signed into law on July 9, 2012.
Prior to the passage of the FDASIA, sections 301(e) and 301(f) of the Food, Drug, and Cosmetic Act (FD&C Act) prohibited drug facilities from denying FDA: (1) entry or the opportunity for inspection or; (2) refusing access to or the opportunity to copy specific records. Section 707 of the FDASIA extends this prohibition, through section 501(j) of the FD&C Act, by deeming a drug 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." This provision extends to "any factory, warehouse, or establishment in which … drugs … are manufactured, processed, packed, or held, for introduction into interstate commerce or after such introduction, or to enter any vehicle being used to transport or hold such … drugs … in interstate commerce." FDASIA also adds section 704(a)(4) to the FD&C Act, allowing FDA to "request, in advance of or in lieu of an inspection, within a reasonable timeframe, within reasonable limits, and in a reasonable manner, records or information that FDA may inspect under section 704(a)."
Any FDA investigation of a drug facility or of drug facility documents has to be done "at reasonable times, within reasonable limits, and in a reasonable manner." A drug facility may delay, deny, limit or refuse FDA investigations with "reasonable explanation," which would prevent a drug from being deemed adulterated. Interestingly, FDA acknowledges the absence of a definition for "reasonable" within the FD&C Act, noting that "FDA intends to work with facilities to conduct inspections and procure the information necessary to achieve the objective of the inspection." This absence of a definition for "reasonable" could potentially create issues; what drug facilities may view as "reasonable" for their production and activities may not agree with FDA's view of "reasonable." The final Guidance also states that, even if a "reasonable explanation" is given, a drug facility may "nevertheless violate other provisions of the FD&C Act or other federal or state laws."
Nonetheless, the final Guidance provides examples of the types of delays, denials, limits or refusals that would apply under section 501(j). Such 501(j) delays of inspection include delays in scheduling pre-announced inspections, delays during an inspection and delays in producing records. The final Guidance provides examples of "reasonable" delays and ones that would be unreasonable. With respect to denials under 501(j):
"FDA interprets the word deny to include active behavior 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 FDA from completing an inspection. This includes statements or physical actions intended to avoid inspection or to mislead, deceive, or impede the investigator."
Examples of denials of inspections under section 501(j) include, but are not limited to, rejecting FDA's attempts to schedule a pre-announced inspection and preventing an FDA investigator from beginning an inspections. Further, when an owner, operator or agent of a drug facility prevents FDA from conducting a full inspection, that person is deemed to be limiting the inspection under this statute. Such actions include limiting photography, limiting access to or copying of records and limiting or preventing collection of samples. More specific examples of each of these types of limitations are detailed in the final Guidance. Lastly, according to the FDA, refusal to permit an inspection includes both active and passive behavior, as well as non-action on the part of the owner, operator or agent of the drug facilities. Examples of refusals under 501(j) include, but are not limited to, barring an FDA investigator from entering into a facility or portions of a facility and failing to respond to FDA's attempts to contact the facility to schedule an inspection.
It will be interesting to see whether FDA intends to apply its approach in this final Guidance to other FDA-inspected facilities, such as medical device facilities and facilities that handle combination products. Though the final Guidance relates only to drug inspections, it states that "facilities subject to inspection under any of the authorities in section 704 of the FD&C Act, even if some other authorities in that section may be limited or inapplicable," will be covered by this guidance. Contentions arising from the boundless terms provided in this final Guidance are likely.