Guidance Breakdown: Delaying, Denying, Limiting, or Refusing a Drug or Device Inspection
The FDA defines the types of behaviors it considers to constitute delaying, denying, or limiting inspection, or refusing to permit entry.
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The FDA's power to inspect drug and device facilities is a cornerstone of its authority. The agency’s recent final guidance on what constitutes delaying, denying, limiting, or refusing an inspection is critical for anyone in the industry.
This guidance stems from the FDASIA of 2012, which added section 501(j) to the FD&C Act. This section deems a drug or device adulterated if its inspection is delayed, denied, limited, or refused. The FDA Reauthorization Act of 2017 (FDARA) extended this scope to include devices.
The guidance finalizes the draft guidance of the same title issued on December 16, 2022 (87 FR 77125), and supersedes the October 2014 guidance entitled, “Circumstances that Constitute Delaying, Limiting, or Refusing a Drug Inspection”, which is withdrawn.
Background
Section 704 of the FD&C Act grants FDA the authority to inspect facilities at reasonable times, within reasonable limits, and in a reasonable manner. This includes reviewing records, accessing areas of the facility, and observing manufacturing processes. Facilities must comply with inspection requirements to avoid their drugs or devices being deemed adulterated. Registration and updating contact information are crucial for facilitating inspections.
Delay of inspection
A few points here:
Pre-announced Inspections: The FDA usually does not pre-announce for-cause and routine surveillance inspections for drug facilities but does for pre-approval, pre-license, and foreign facility inspections. Pre-announcement is required by section 704(h) for foreign and domestic device establishments.
Scheduling Delays: Examples of unreasonable delays include not agreeing to a start date, requesting a later date without explanation, and not responding to FDA contact attempts. Reasonable explanations might include non-operational manufacturing periods.
Delays During Inspections: Examples include restricting access to operational areas without a reasonable explanation, leaving investigators without the necessary documentation, and not having necessary personnel available. Reasonable delays include following gowning procedures or safety training requirements.
Producing Records: Delays in providing requested records without reasonable explanations can constitute delaying an inspection. Reasonable explanations include translation needs or large volumes of records requiring time to compile.
Denial of inspection
Denying an inspection can be more straightforward but equally detrimental. Examples include:
Refusing to schedule a pre-announced inspection.
Not allowing inspection upon FDA arrival.
Claiming the facility does not engage in drug or device activities without basis.
Sending staff home and claiming no production activities are occurring.
Acceptable reasons might include facility closure for maintenance or the absence of personnel to answer questions during unannounced inspections.
Limiting of inspection
Limiting inspections involves restricting the FDA's access or ability to conduct a thorough review:
Access to Facilities and Processes: Examples include stopping production during an inspection or not allowing observation of certain processes. Reasonable limitations might involve following documented safety procedures or OSHA training requirements before access.
Photography: The FDA relies on photographs to document conditions. Preventing photography without valid reasons, such as product quality concerns, is considered limiting. For example, documenting conditions like rodent infestation or improper maintenance through photos is crucial for the FDA's inspection process.
Access to or Copying of Records: This includes not allowing access to certain records, providing incomplete records, or manipulating electronic records. Redacting non-inspectional data or providing full electronic records as required are considered reasonable.
Collection of Samples: Preventing the FDA from collecting necessary samples, such as environmental or raw material samples, also falls under limiting inspections.