USFDA INSPECTION SYSTEMS

Inspection:

The Food and Drug Administration (FDA) conducts inspections and assessments of regulated facilities to determine a firm’s compliance with applicable laws and regulations, such as the Food, Drug, and Cosmetic Act and related Acts.

Types of Inspections:

FDA conducts several types of inspections to help protect consumers from unsafe products:

• Pre-approval inspection: After a company submits an application to FDA to market a new product
• Routine / surveillance / GMP inspection: routine / periodic inspection of a regulated facility
• “for-cause” inspection: To investigate a specific problem that has come to FDA’s attention
• Post-approval inspection: To verify product life cycle management.

Commonly used forms by FDA:

• FDA 482 – Notice of Inspection
• FDA 483 – List of Observations
• FDA 484 – Receipt for Samples
• FDA 463 – Affidavit Special purpose affidavits
• EIR – Establishment Inspection Report

Enforcement mechanisms:

Form 483 observations

Warning Letter

Import ban

Consent Decree

Injunction

Legal Proceedings

Penalties

Types of Conclusion:

The conclusions of the inspection are reported as Official Action Indicated (OAI), Voluntary Action Indicated (VAI), or No Action Indicated (NAI).

• NAI (No Action Indicated): An NAI inspection classification occurs when no objectionable conditions or practices were found during the inspection or the significance of the documented objectionable conditions found does not justify further actions.
• VAI (Voluntary Action Indicated): A VAI inspection classification occurs when objectionable conditions or practices were found that do not meet the threshold of regulatory significance. Inspections classified with VAI violations are typically more technical violations of the FDCA (The United States Federal Food, Drug, and Cosmetic Act).
• OAI (Official Action Indicated): An OAI inspection classification occurs when significant objectionable conditions or practices were found and regulatory action is warranted to address the establishment’s lack of compliance with statute(s) or regulation(s).

Definition: Warning letter is a formal advise to a firm communicating the agency’s position on a matter but does not commit FDA to taking enforcement action.

The agency’s policy is that Warning Letters should be issued for violations which are of regulatory significance. Failure to adequately and promptly take corrections may be expected to result in enforcement action.

Reasons for a Warning letter:

• Continual non-conformance from GMPs and deviation from the systems
• Repeated Form 483 observations over several audits and inspections for GMP violations
• Repeated unsatisfactory response or no response to warning letter and 483 observations
• Failure of company to correct deficiencies
• Data integrity and offline recording

Injunction: 

An order issued by the Court requiring a defendant to do or refrain from doing a specified act

Consent Decree: 

An injunction to which the defendant has agreed and which is filed in court of law

Impact of the Decree:

• Financial Impact
• Fines & Forfeiture of profits
• Injunction on selling of drugs
• Delays in approvals
• All other facilities come under scrutiny
• Can lead to close down of company.

• Compliance Impact
• Hire consultants to enable compliance
• Retraining, Complete missing or inadequate studies
• Expert certification

If no enforcement action is contemplated, or after enforcement action is concluded, FDA provides inspected establishments with a final inspection report, called an Establishment Inspection Report (EIR), which includes:

• Brief history of prior inspectional findings, including any action taken by FDA or corrective action taken by the firm in response to a previous inspection
• The investigator’s narrative report
• Any refusals, voluntary corrections, or promises made by the firm’s management
• Copies of forms the FDA issued to the firm during the inspection, including the FDA Form 483.