Section 704 of the Federal Food, Drug, and Cosmetic Act (FDCA) authorizes FDA to conduct inspections at reasonable times, within reasonable limits, and in a reasonable manner. Furthering the agency’s duty to conduct inspections, if a drug 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,” that drug is deemed to be “adulterated” under the Food and Drug Administration Safety and Innovation Act (FDASIA) of 2012.
In July 2013, FDA published the draft guidance “Circumstances that Constitute Delaying, Denying, Limiting, or Refusing a Drug Inspection,” finalized in October 2014, explaining the types of behaviors (i.e., actions, inactions, and circumstances) that FDA considers to constitute “delaying, denying, or limiting inspection, or refusing to permit entry or inspection” under the law. Then, in 2017, the FDA Reauthorization Act (FDARA) amended the FDCA such that [as was already the case with a drug or biologic] a medical device is also deemed to be “adulterated” if the owner, operator, or agent of the factory, warehouse, or establishment at which the device is manufactured, processed, packed, or held delays, denies, or limits an FDA inspection. In response, last week, FDA published revised draft guidance that, when finalized, will supersede the October 2014 final guidance and expand its applicability to also cover medical devices.
In the revised draft guidance, FDA explains how it will consider reasonable explanations for behavior that may otherwise be considered to be delaying, denying, limiting, or refusing an inspection. With limited exceptions, the recommendations that FDA provides in the revised draft guidance for device manufacturers are the same as the recommendations that FDA has been providing for drug makers. One exception is that whereas FDA is not required to pre-announce inspections at drug facilities, the revised draft guidance notes that FDA is required to pre-announce inspections (other than for-cause inspections) at device establishments.
The draft guidance provides examples of delays in scheduling a pre-announced inspection that may cause drugs or devices to be deemed “adulterated” by FDA, including when:
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A facility will not agree to an announced inspection start date and does not give a reasonable explanation for its failure to do so.
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After scheduling an inspection, a facility requests a later start date without giving a reasonable explanation.
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A facility fails to respond following FDA’s attempts to contact the facility’s designated contact(s).
However, FDA’s guidance notes, there may be potentially reasonable explanations for scheduling delays that the agency would consider, including when manufacturing at the facility in question is not ongoing.
The guidance also provides examples of delays during an inspection that may cause drugs or devices to be deemed “adulterated,” and of potentially reasonable explanations for those delays. New in the 2022 draft guidance, FDA points out that it might be unacceptable for a facility to agree to a pre-announced inspection date, but then when the investigator enters the facility, the necessary facility personnel are not available, or the firm’s management informs the investigator that operations are shutdown, without reasonable explanation. Also new in the guidance, FDA says a reasonable explanation for that delay may be that a “device facility does not provide FDA investigator access to environmentally controlled areas until the investigator accommodates the facility’s precautionary measures to prevent contamination and risk of personal safety.”
FDA also offers examples of behavior that the agency would consider to constitute a limitation of an inspection that could cause drugs or devices to be “adulterated,” adding into the new draft guidance the example of a firm interrupting production activities to prevent FDA investigators from observing production operations. Also new is FDA’s note that it may be reasonable for investigators’ photography to be limited by a facility so long as that facility can document that taking photographs of any raw material or assembly would adversely affect product quality.
The revised draft guidance describes how FDA’s ability to access and copy records is a critical aspect of agency inspections, providing two new examples, applicable to both devices and drugs, of when it would be unreasonable for a facility to limit access to records:
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A facility maintains electronic records but omits or limits the data contained in the electronic records when providing electronic copies of the records to FDA. This includes but is not limited to actions such as removing data columns in Excel, removing data from the electronic record when providing the record to FDA, exporting data into reports without including all of the data fields (unless otherwise requested by FDA), or locking the electronic worksheet so that the data cannot be searched, sorted, or analyzed by FDA.
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A facility identifies an electronic record as the original but does not provide an electronic copy of that record (or data query) to FDA pursuant to FDA's request.
While many might view these examples as common sense, FDA investigators have clearly encountered enough such circumstances that the agency felt that providing clarity and notice in the form of a guidance document was necessary. As is woven throughout the guidance document, the agency is willing to entertain explanations for why certain information may not be readily available or for why it may take longer than usual for information to be provided, but the agency is looking to call a spade a spade when it perceives companies to be obfuscating, delaying, obstructing or thwarting an inspection. In our experience that rarely occurs because of a single event, but rather is the result of a number of circumstances that leave the investigator with the impression that the company is being less than candid and forthright. Companies should in all cases, act with all due haste during an inspection and explain challenges when they occur coupled with their plan for addressing it, as challenges almost always occur in one form or another. So long as the company is able to convey that it is doing its best to provide the investigator with the requested information, few companies should have reason to worry that FDA may consider their behavior to rise to the level of being a refusal.
FDA is accepting comments on the revised draft guidance through February 14, 2023. If you may wish to submit a comment, or have any questions on medical device inspections more generally, please contact any of the authors of this alert or the Hogan Lovells attorney with whom you regularly work.
Authored by Jodi K. Scott, David Horowitz, Mike Heyl, and Blake Wilson
