What is an FDA pre-approval inspection (PAI)?

1What a pre-approval inspection is.

FDA may approve a new drug application (NDA) or abbreviated new drug application (ANDA) if, among other requirements, the methods, facilities and controls used to make and test the drug are found adequate to ensure and preserve its “identity, strength, quality, and purity”.¹ A pre-approval inspection (PAI) is how FDA checks that on site. Compliance Program 7346.832 says preapproval evaluations and inspections ensure that any establishment named in or referenced in an application “can perform the proposed manufacturing operations in conformance with CGMP requirements and that data submitted in the application are accurate and complete”.¹

FDA’s Investigations Operations Manual names pre-approval, pre-market and pre-license inspections as one of three general categories of inspection, alongside surveillance and for-cause inspections, conducted “when necessary, as part of the review of an application”.² FDA says application-based inspections are conducted for about 20% of the application reviews it carries out.³

Compliance Program 7346.832 covers PAIs of manufacturing facilities named in pending NDAs and ANDAs. Prelicense inspections and PAIs for biologics license applications follow Compliance Program 7346.832M instead.¹ PAIs are not included in FDA’s public database of inspection classifications.⁴

2How FDA decides whether a site needs one.

When an application arrives, CDER assembles an integrated quality assessment (IQA) team, which decides from a cumulative risk assessment whether each facility listed needs a PAI.¹ It weighs what the facility will do against what FDA has already evaluated or inspected there, the facility’s compliance status and inspection history, the product’s characteristics, such as a novel or complex drug, and hazard signals such as recalls, complaints, field alert reports and MedWatch reports. A PAI can also be triggered to confirm the accuracy and reliability of the quality data in the application, or that the facility’s operations match those proposed.¹

FDA can use alternative tools in lieu of or in advance of a PAI: inspection reports from Mutual Recognition Agreement partners and other trusted regulators, remote interactive evaluations, and requests for records under section 704(a)(4) of the FD&C Act.¹ That section lets FDA require records from a drug manufacturer “in advance of or in lieu of an inspection”, with a request that describes the records and gives a rationale.⁵

Within 60 calendar days of receiving an NDA or ANDA, CDER’s Office of Pharmaceutical Manufacturing Assessment (OPMA) either requests a PAI from FDA’s Office of Inspections and Investigations (OII) or enters a facility recommendation.¹

3When the site hears, and what FDA prepares.

The FD&C Act does not require FDA to pre-announce drug inspections, but FDA’s general practice is to contact the firm before a pre-approval or pre-license inspection.⁶ When FDA needs to inspect while the product is being made, it notifies the facility so it can adjust its manufacturing schedule; for original NDAs, FDA’s goal is to give at least 60 days’ notice and no later than midcycle.¹ FDA still reserves the right to inspect at any time during the review cycle. A site that is not ready should give a written explanation and the date it will be available.¹ An unreasonable delay in scheduling a pre-announced drug inspection can cause the drugs made there to be deemed adulterated under section 501(j) of the FD&C Act.⁶

PAIs are led by OII, with CDER staff taking part when appropriate. Before the inspection the team lead studies the chemistry, manufacturing and controls (CMC) section of the application and related drug master files, reviews the pharmaceutical development section where possible, and reviews the firm’s history and earlier Form FDA 483 observations. IQA team members give their concerns in writing beforehand.¹

4The four objectives.

The programme sets four inspection objectives. Some are covered on every PAI; others depend on risk.¹

For the data audit, finished product stability, dissolution, content uniformity and API impurity data are generally good candidates. The programme’s signs of a data integrity problem include substituting passing data for failing data without sufficient investigation, improperly invalidating out-of-specification results, unexplained gaps in a chromatographic sequence, backdating stability results and using results from earlier batches in place of testing another batch.¹ It distinguishes factual integrity, where raw data correspond directly to what was submitted, from contextual integrity, where the surrounding records, such as a complete chromatographic sequence, support it. If a pattern of data reliability issues appears, the team lead should consider expanding coverage to marketed products under Compliance Program 7356.002.¹

5How a PAI ends.

Reportable observations are issued on Form FDA 483. For a PAI they include differences from the filed CMC description, a commercial batch record not specific enough for reproducible manufacture, missing or unreliable data, a pattern of disregarding test results and weaknesses in analytical method validation.¹ A Form 483 is not FDA’s final determination that a condition violates the law; FDA considers it with the establishment inspection report, the evidence collected and the company’s response.⁷ The firm sends its response electronically to OPMA.¹

The team lead passes concerns and any Form 483 to the preapproval program manager (PAM) within 2 business days of closing the inspection. The PAM enters a recommendation no later than 20 business days after the close, and always before the user fee date; OPMA’s facility assessor makes the final recommendation.¹

FDA does not withhold solely because commercial-scale process validation is incomplete at the time of the PAI, but the firm must achieve “a high degree of assurance” that the process consistently produces product meeting its quality attributes before distribution.¹ After a withhold, OPMA’s decision to recommend approval depends on satisfactory correction of the findings, and a follow-up inspection may be needed to confirm it. When the site markets no FDA-regulated products, a warning letter is not usually the appropriate action.¹

6The current programme, issued June 2026.

FDA issued the current Compliance Program 7346.832 on 29 June 2026, with an implementation date of 10 August 2026. FDA describes it as revised “to further strengthen the risk-based strategy to make a prompt decision on the need for inspections and promote efficient conduct of the inspections”, with updated roles and responsibilities.¹ It refers to FDA’s September 2025 guidance on alternative tools for assessing facilities named in pending applications.¹

7How it runs in Seal.

A PAI asks whether the filed CMC content matches the site’s records and whether the raw data behind it hold up. In Seal’s regulatory submissions workflow, each section keeps the studies, batches and results it rests on, with missing evidence recorded, so an authority question is answered from the records behind the original content. Commitments made to an authority keep their due date, owner, required evidence and fulfilment status.

On the day, inspection readiness logs each request with its verbatim wording, agreed interpretation, owner and the evidence delivered, keeps each delivered package with its source record versions, and turns observations into commitments linked to CAPA and verification. Neil can prepare a commitment evidence review that maps each commitment to its completion evidence; regulatory and quality owners approve any external response.