STANDARD OPERATING PROCEDUREPage 1 of 7
Document Number: S-144 Version 1.00
Responding to FDA Warning Letters

Standard Operating Procedure

Responding to FDA Warning Letters

This is an example of a Standard Operating Procedure. It is a proposal and starting point only. The type and extent of documentation depends on the process environment. The proposed documentation should be adapted accordingly and should be based on individual risk assessments. There is no guarantee that this document will pass a regulatory inspection.

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Company Name: /
Controls:
Superseded Document / N/A, new
Reason for Revision / N/A
Effective Date / March 1, 2015
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Author / I indicate that I have authored or updated this SOP according to applicable business requirements and our company procedure: Preparing and Updating Standard Operating Procedures.
Name:______
Signature:______
Date:______
Approver / I indicate that I have reviewed this SOP, and find it meets all applicable business requirements and that it reflects the procedure described. I approve it for use.
Name:______
Signature:______
Date:______
Reviewer / I indicate that I have reviewed this SOP and find that it meets all applicable quality requirements and company standards. I approve it for use.
Name:______
Signature:______
Date:______

1.PURPOSE

Serious violations identified during FDA inspections are documented in FDA Warning Letters that are mailed to the company management. A well-reasoned, complete and timely responseis extremely important to possibly mitigate an FDA compliance decision for further action, e.g. import alert, product seizure or consent decreee. This SOP will help to effectively respond to FDA warning letters.

2.SCOPE

Responding to FDA Warning Letters. The procedure is also applicable to other regulatoryinspection reports that require a response to violations.

3.GLOSSARY/DEFINITIONS

Item / Explanation
Inspectional Observation
(483 form) / When an FDA inspector finds non-compliance he/she will write an inspectional observation during the inspection. Inspectors use a special form, the so-called 483 (form).A 483 is actually an inspectional observations form that the FDA uses to convey to you the issues they have observed during their audit or inspection. The information can be handwritten or typed using a typewriter or a computer and is handed over to the company at the conclusion of the inspection.
EIR / Establishment Inspection Report. Written after an FDA inspection by the agency. The observations from 483's are classified as No Action Indicated (NAI), Voluntary Action Indicated (VAI) or Official Action Indicated (OAI).
Warning Letter / Sent to a company if significant deviations from regulations have been found during an FDA inspection. The purpose of a warning letter is to notify the firm’s senior management that the company is in violation of the law and that the FDA is ready to take regulatory action if voluntary corrections are not accomplished.
CAPA / Corrective and preventive action plan

Note: For other definitions see

4.REFERENCE DOCUMENTS

4.1.FDA Inspection Survival Guide
Part of Labcompliance Best Practices Package: FDA Inspections
Order from

4.2.SOP S-141: FDA Inspections – Preparation, Conduct and Follow-up, Available through

5.RESPONSIBILITIES

5.1.Quality Assurance

5.1.1.Overall responsibility for inspections and responding to the Warning Letter.

5.1.2.Trains employees on the meaning of a Warning Letter.

5.1.3.Recruits a response team

5.2.Response team and team leader

5.2.1.Manages process to identify root causes and corrective action plans for each reported violation

5.2.2.Drafts a response to the Warning Letter

5.2.3.Gets the response approved

5.2.4.Monitors the progress and verifies the efficiency of the corrective action

5.3.Functional Supervisors(Laboratory/Manufacturing)

5.3.1.Help to develop corrective action plans and commits to provide resources

5.3.2.Makes sure that the necessary people are available for suggested corrective actions.

5.4.Management

5.4.1.Dedicates resources that are required for preparation, conduct and follow-up

5.4.2.Agrees to corrective actions and provides resources.

5.4.3.Approves the response to the FDA

5.5.Regulatory Affairs

5.5.1.Provide members to the response team.

5.5.2.Communicate with the FDA

6.PROCEDURE

6.1.Preparing a corrective action plan

6.1.1.Once warning letter is received, management informs the responsible QC manager.

6.1.2.The QA manager forms a response team with members from QA, regulatory affairs and operational departments. Members from the operational departments should be most qualified people.

6.1.3.Under the supervision of the response team leader the team prepares a table with all violations and suggestions for root causes and corrective actions. The form in attachment 7.1is used.

6.1.4.If root causes cannot be obviously identified for specific observations, sub-teams should be formed to investigate details.

6.1.5.If root causes can ne be identified by company employees experienced consultants should be hired to get outside assistance..

6.1.6.The response team develops an action plan to achieve immediate short-term and long-term correction and to prevent local and global recurrence. The plan documents steps for all corrective actions with owners, deliverables, due dates and methods of verification for each step. The form in attachment 7.2 is used for this.

6.1.7.Management reviews and approves the corrective action plan

6.2.Response to the FDA

6.2.1.The response team leader drafts a letter to the FDA. Important points are

  • The letter should be sent not later than 12 days after theWarning Letter has been received.
  • The letter should start with a clear commitment/statement from senior leadership to comply with regulations.
  • Each violation should be addressed separately in the same chronological order as listed on the Letter.
  • If a single violation consists of several deviations, each deviation should be answered separately.
  • Responses should be as specific as possible, for example, statements such as “We will fix this SOP” are not sufficient
  • Note whether the company agrees with the stated violation
  • If there is disagreement with one or more violations, the response should be based on facts and has verifiable data and supporting documentation.
  • Make it clear that the root root causes for violationsare understood or what actions are taken to get them clarified.
  • Indicate whether the violation is an isolated incident or a more general site or global issue.
  • For each violation a corrective action plan should be submitted. Describe why the corrective action will resolve the problem locally and globally and does not occur again.
  • The table listing all observations together with corrective actions as developed in 6.1.3 is attached to the response.
  • Document the impact of violations on other applications/systems and attach an action plan on how to avoid similar deviations elsewhere.
  • Include a realistic time frame for the corrective action plan. Realistic means that the time is acceptable by the FDA and is doable by the company.
  • If corrective/preventive actions have already started or some are finished, attach supporting documents to the letter
  • The table listing all steps, owners, deliverables and due dates as developed in 7.2should be attached to the response letter
  • The letter is reviewed and approved by department supervisors and management
  • The regulatory affairs manager sends the letter to the FDA district director
  1. Follow-up
  2. The corrective action plan is implemented in affected departments
  3. The response team monitors each corrective action plan and prides status reports every month.
  4. All of the following should be retained:
  5. The warning letter
  6. All tables from attachment 7.
  7. All correspondence with the FDA.
  8. All meeting notes, these also include notes taken during telephone conferences.

7.ATTACHMENTS

7.1.Attachment – Violations and suggested corrective actions

Item # / Violation / Corrective Action / Status

7.2.Attachment – Corrective Action Plan

Violation #: ______

Corrective Action:______

Step # / Action / Deliverable / Owner / Due Date / Completed
Date / Method for
Verification

(Replace with your company’s name) FOR INTERNAL USE