FDA Guidance on Delaying, Denying, Limiting, or Refusing Drug or Device Inspection

The FDA guidance “Circumstances that Constitute Delaying, Denying, Limiting, or Refusing a Drug or Device Inspection” published in June 2024 outlines the behaviors and circumstances that the FDA considers to be non-compliant with inspection requirements under section 501(j) of the Federal Food, Drug, and Cosmetic Act (FD&C Act). This guidance is essential for ensuring that drugs and devices are not deemed adulterated due to inspection-related issues.

The guidance aims to make sure transparency and compliance during FDA inspections to protect public health by ensuring that drugs and devices are manufactured by regulatory standards.

Legal Background

The Food and Drug Administration Safety and Innovation Act (FDASIA) of 2012 added section 501(j) to the FD&C Act, which deems a drug adulterated if the owner, operator, or agent of a facility delays, denies, or limits an FDA inspection, or refuses to permit entry or inspection.

The FDA Reauthorization Act of 2017 extended these provisions to include medical devices.

Scope

The guidance applies to all facilities involved in the manufacture, processing, packing, or holding of drugs or devices. It defines what constitutes delaying, denying, limiting, or refusing an inspection, providing specific examples to illustrate these behaviors.

Examples of Non-Compliant Behaviors:

Delaying: Postponing an inspection without a reasonable explanation.
Denying: Explicitly refusing to allow an inspection to take place.
Limiting: Restricting the scope of an inspection, like limiting access to certain areas or records.
- I want to stress that this includes the situation where a facility provides some, but not all, records requested by the FDA investigator that FDA has authority to inspect. Everyone’s favorite delaying tactic.
- This also includes omitting or limiting the data contained in the electronic records when providing electronic copies of the records to FDA. This includes but is not limited to actions like 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.
- Preventing an authorized representative of FDA from collecting statutorily authorized samples may be considered limiting the inspection. Examples of sample limitations include, but are not limited to, declining to allow or impeding FDA from collecting the following types of samples: environmental samples, finished product samples, raw material samples, in-process material samples, reserve samples in bioequivalence and bioanalytical studies, and labeling.
Refusing: Not allowing the FDA to enter the premises for inspection.

Background on FDA Guidance

The FDA issues guidance documents to communicate its current thinking on regulatory issues. These documents are not legally binding but give insight into how the FDA interprets and enforces laws and regulations. The guidance on delaying, denying, limiting, or refusing inspections was necessitated by the need to clearly define what constitutes non-compliance under section 501(j) of the FD&C Act. This clarity helps facilities understand their obligations and avoid actions that could lead to their products being deemed adulterated.

The guidance was finalized to replace the previous version issued in October 2014 and incorporates feedback and updates to reflect current practices and challenges in the inspection process. It is a critical tool for both the FDA and industry stakeholders to ensure that inspections are conducted smoothly and effectively, thereby safeguarding the quality and safety of drugs and devices available to the public.

Computer Software Assurance Draft

The FDA published on 13-Sep-2022 the long-awaited draft of the guidance “Computer Software Assurance for Production and Quality System Software,” and you may, based on all the emails and posting be wondering just how radical a change this is.

It’s not. This guidance is just one big “calm down people” letter from the agency. They publish these sorts of guidance every now and then because we as an industry can sometimes learn the wrong lessons.

This guidance states:

Determine intended use
Perform a risk assessment
Perform activities to the required level

I wrote about this approach in “Risk Based Data Integrity Assessment,” and it has existed in GAMP5 and other approaches for years.

So read the guidance, but don’t panic. You are either following it already or you just need to spend some time getting better at risk assessments and creating some matrix approaches.

FDA Final Guidance on Recalls

The FDA published the final guidance for “Initiation of Voluntary Recalls Under 21 CFR Part 7, Subpart C” in March of 2022.

Nothing new here really, as the FDA has just finalized recommendations that companies make adequate preparations to operations in advance of when a recall may be needed (e.g., prepare and execute a recall communications plan). In addition to these preparations, the FDA recommends that companies consider preparing, maintaining, and documenting written procedures (in paper or electronic format) for initiating a recall and performing actions related to initiating a recall. Moreover, the document addresses how companies should develop a recall strategy and train personnel on executing a recall, as well as how companies should use adequate product coding.

Guidances in Administrative Law

Edward Rubin over on the Administrative Law JOTWELL, in the post “Uncovering the Hidden World of Administrative Guidance” exposed me to the 2019 article by Nicholas R. Parrillo “Federal Agency Guidance and the Power to Bind: An Empirical Study of Agencies and Industries” which I just find fascinating.

Guidances are an interesting part of our job. As a best practice, they show one way to get to the desired end result, but there can be other ways but the presence of guidance can obscure those possibilities. Often times if an agency goes to the level of detail to show you what good looks like you’d be foolish not to try to meet them there. Other times guidance can be a real head scratcher.

Good article, and of interest to the non-lawyers like myself who have to live within the boundaries.

Good practices for research and development facilities (WHO draft guideline)

Last month the World Health Organization published a draft guideline on Good practices for research and development facilities.

This arrow pretty much sums it up:

Seriously, not much surprising here. What this guide definitely does is place early research in the framework of Q10 and point out that there is one quality system to rule them all and that level of rigor is based on risk.

Give it a read.