Pre-approval Inspections: FDA introduces New Guidance

The US Food and Drug Administration (FDA) is currently revising its guidance on pre-approval inspections (PAI). The most significant change concerns the introduction of a risk-based approach when deciding on the necessity of such an inspection and on alternative methods to on-site inspections.

The updated document will come into force on 10 August 2026 and will replace an earlier version dated October 2022.

The core elements of a PAI remain:

• Assessment of a manufacturer's readiness for commercial production
• Assessment of compliance with marketing authorisation conditions
• Data integrity
• Demonstrated commitment to quality as early as the pharmaceutical development stage.

The current revision, moving towards more risk-based approaches, is intended to speed up decisions on the need for inspections and promote the efficient conduct of inspections.
The document states: "The FDA employs a risk-based strategy to determine the need, timing and conduct of a PAI in support of the regulatory action on an application. The risk-based approach, such as the use of inspection history and alternative tools, streamlines the FDA's oversight of pharmaceutical manufacturing establishments and operations and enables a prompt and efficient evaluation of an establishment's readiness to conduct manufacturing operations as described in the application."

As part of the decision-making process, in addition to product and manufacturing risks, the manufacturing processes and activities described in the application, as well as further relevant information on processes and facilities, compliance and inspection history, and quality history, are assessed. A flowchart has been developed to illustrate this process.

A further new section describes alternative tools to support PAIs, such as requesting existing inspection reports and other information, including from foreign regulatory authorities, or conducting remote regulatory assessments.