FDA Inspection Reports: What is What

Recommendation

13/14 December 2023
Berlin, Germany

Root Cause Analysis
A CAPA Workshop on Successful Failure Investigation

Repeatedly we receive questions with regard to the various inspection reports of the U.S. Food and Drug Administration (FDA). Following we will introduce the three main documents:

Form 483

This form with the eponymous number 483 is used by the executing Inspector (FDA Investigator) to document the deficiencies he found. It is issued at the end of the inspection and should be answered officially. This response is expected within 15 working days after its issuance. Only then it is guaranteed that the statement will be taken into account in a possible Warning Letter (see below). Sometime, in the case of reasonable compliance, no 483 is issued.

EIR: Establishment Investigation Report

The EIR is also created by the Inspector in addition to the form 483. This should be done within 30 working days. The EIR is then examined by the responsible Center or District Office of the FDA, issuing the following statuses: 

• NAI: No Action Indicated - there were no objectionable items found during the inspection 
• VAI: Voluntary Action Indicated - objectionable items were found, but no action is required on the part of the authority. All of the company's actions are on a voluntary basis. 
• OAI: Official Action Indicated - objectionable items were found and further regulatory measures will be derived (e.g. Warning Letter).

The EIR is forwarded to the inspected company. As part of the so-called 'Freedom of Information Act' it can also be requested by other companies, though. But experience has shown that the disclosure of a foreign EIR may take some time.

Warning Letter

This is mainly issued when serious defects were identified but also if the answer to the Form 483 is classified as inadequate. It is released - after a review by the responsible Center/ District Offices, not the Inspector himself. The company must respond within 15 working days and explain in detail how to resolve the deficiencies on the one hand and how a recurrence can be prevented on the other hand. Warning Letters are generally published on the homepage of the FDA.

In the aftermath,  other unpleasant consequences for the company may apply:

• Influence on the approval
  The authorisation for one or more products will not be granted. Applications will not be processed. 
• Import Stop / FDA Import Alert
  The company's product (or products) may no longer be imported into the United States. The goods remain at customs. 
• Debarment List
  This list comprises all persons who are not allowed to produce pharmaceutical products for the American market. The Debarment List is freely available. 
• Court - Consent Decree
  For American companies and its subsidiaries it can be obtained legally that for several months to years a consulting company will check the company and streamline systems and processes. A final inspection is carried out at the end. In the meantime, profits can be skimmed off.