Tag: FDASIA

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.

Section 711 of FDASIA and Regulatory Obligations

Too often, I see folks in pharma focus on 21 CFR Chapter 1, or at best all three chapters, maybe know the guidances and pay attention to little else. Unfortunately, that approach will often get one in trouble.

Section 711 of the Food and Drug Administration Safety and Innovation Act (FDASIA) amended the Federal Food, Drug, and Cosmetic Act (FD&C Act) to enhance the safety and quality of the drug supply chain. Specifically Section 711 amends Section 501(a)(2)(B) of the FD&C Act by adding the following sentence:

“For purposes of paragraph (a)(2)(B), the term ‘current good manufacturing practice’ includes the implementation of oversight and controls over the manufacture of drugs to ensure quality, including managing the risk of and establishing the safety of raw materials, materials used in the manufacturing of drugs, and finished drug products.”

This amendment clarifies that current good manufacturing practice (CGMP) requirements for drugs include:

  1. Implementing oversight and controls over the entire manufacturing process to ensure quality.
  2. Managing the risks related to raw materials, other materials used in manufacturing, and finished drug products to establish their safety.

In essence, Section 711 expands the FDA’s CGMP authority to explicitly cover supply chain management and drug manufacturers’ oversight of their suppliers and contract manufacturing operations. It also allows the FDA to enforce supply chain control requirements during inspections.

The legislative history shows that Congress intended to significantly expand the FDA’s authority over the increasingly global drug supply chain through this provision. It allows the FDA to scrutinize how manufacturers select, qualify, and oversee suppliers of raw materials and contract manufacturers to ensure drug quality and safety.

Please note that the FDA gets this expanded authority without revising 21CFR. That’s how it works; Congress can do that. Will we eventually see some 21 CFR updates? I have no idea.

But what this does mean is that the FDA has the authority to:

  1. Inspect risk management for GMPs, and assume you have it. What does good risk management look like? The agency has adopted ICH Q9(r1) as guidance, so start there.
  2. Inspect your supplier management, which includes qualifying and overseeing suppliers and contract manufacturers.

I’ve started to receive regulatory intelligence that this is coming up in inspections. Expect to be asked for the risk management evidence and for supplier qualification and oversight evidence.