FDA Warning Letter

A guide for how to survive a FDA Warning letter. So you got at FDA 483 and now you have a FDA Warning Letter, learn how to survive the storm. For more information go to http://compliance-insight.com/fda-483-warning-letters/

1. FDA Warning Letters A Compliance Officer’s Guide to Surviving the Storm Compliance Insight, Inc. 513-860-3512 Copyrighted 2013

2. What is an FDA Warning Letter The United States Food and Drug Administration defines a Warning Letter as "...a correspondence that notifies regulated industry about violations that FDA has documented during its inspections or investigations. Typically, a Warning Letter notifies a responsible individual or firm that the Agency considers one or more products, practices, processes, or other activities to be in violation of the Federal Food, Drug, and Cosmetic Act (the Act), its implementing regulations and other federal statutes. Warning Letters should only be issued for violations of regulatory significance, i.e., those that may actually lead to an enforcement action if the documented violations are not promptly and adequately corrected. A Warning Letter is one of the Agency’s principal means of achieving prompt voluntary compliance with the Act.”

3. Why you’ve received an FDA Warning Letter… Documents a violation of law or regulation Establishes that a firm or person has been notified of the violation Your response to the FDA 483 may have been deficient Designed to promote voluntary compliance Stepping stone to regulatory action

4. What does this letter mean for you and your firm? Warning Letter is considered to be “prior notice” Respond within 15 days FDA will initiate necessary action if no response is received Time is CRITICAL – you have to organize, understand, resolve and respond to the FDA

5. Assessment of the situation Before we begin on the response work, let me say a few words about…

6. Two Approaches To Assessment Focused Assessment – Based specifically on items from the Warning Letter Overall Systemic Assessment – Look beyond the specific items, other areas/products

7. Writing the Response There are some basic rules that can be established regarding writing a response letter. Some or all of these rules may apply depending upon the particular situation of the firm – e.g. lengthy list of observations, serious issues on the warning letter, etc.

8. Writing the Response Someone in a high level in a Quality group (internal or external) should write the response. Personnel copied on the response should include high-level management. This shows that management at the firm is aware of the issues and the commitments being made. Include a cover letter or opening statement. Tell the FDA that you are serious about resolving the issues. State the site address of the audit and the dates.

9. Writing the Response Always remember that you are writing the response to the auditors management – governmental auditing bodies do have supervisors and managers. Do not assume that the person reading the report understands the context of the observation or your reply. Re-state the observation and reference number in the response. Typically, the observation goes directly above the response. If possible, indicate the related compliant systems. This shows that you are in control and that some operations were functioning within acceptable GMP parameters.

10. Writing the Response If the action item is going to take some time to implement, state what will be done in the interim to be compliant with GMPs. Don’t simply indicate that actions will be taken in six months to correct the issue in which you are currently out of compliance without addressing what you will do to be compliant from the current date until the corrections are implemented. If corrective actions have already taken place, indicate the following: Dates implemented Training performed (copies of training sign-up sheets included) Copies of Purchase Orders, installation work, etc. Copies of updated SOPs – indicating what was changed.

11. Writing the Response Define how enhancements will prevent recurrence of the issue observed. Don’t assume that the reader will understand this fact . Explain what will be done to expand, enhance or streamline the compliance system. Don’t forget about training. Allow sufficient time to implement changes to incorporate training that may include proficiency testing.

12. Writing the Response Describe how the firm will monitor the progress and effectiveness of the corrective actions. It may be helpful to explain that despite the issues noted, there has never been an issue. It is not advisable to use this response tactic each time but it can be advantageous for critical observations to state something on the order of “…the product has always met predetermined quality parameters…” Revise, revise, revise. Allow other people not directly involved with the audit to review and comment on the response. They may have insight on response wording that would assist in clarification or strengthening of points.

13. Format of the response How the response should look

14. Indicating corrective actions – taken or planned Restating the observation or comments Defining root cause Developing the due date When initially formulating a response, a 4-Stage Inspection Response Approach may be helpful to develop perceptive on the format of the response and contribute to a better understanding of what actually needs to be implemented to be compliant. This type of approach includes Item 1 Item 2 Item 3 Item 4

15. Cover Letter Example – this is from top level management… We are in receipt of your communication dated --- on -----. We take your communication very seriously and commit ourselves to address your concerns adequately and expeditiously. We will take all the necessary measures to ensure our customers' well-being and safety. Enclosed please find an attachment that addresses your concerns on an individual and on a systematic basis. We agree that a sound Quality System is the result of effective management commitment, dedicated employees, and sound processes and practices. To that end we have retained _____, a reputable consulting firm, to assess our Quality System in greater detail and to help ensure that our Corrective Action plan will address all systemic issues effectively. We have attached a qualification profile for your review.

16. Response Letter – from the response team xx June 20xx   U.S. Food and Drug Administration c/o <name>, Compliance Officer <address> <city>, <state> <zip>   Re: Warning Letter xxx   Dear Mr. xxx:   This letter provides the response from <company name> to the Food and Drug Administration’s (FDA) Warning Letter dated xxx (Attachment 1) related to findings from FDA’s inspection of xxx facility on xxx through xxx. As the Warning Letter notes, xxx responded to the FDA Form 483 on xxx (Attachment 2 for the 483 and original response) but notes that it “did not provide any detailed information regarding proposed corrective actions.” To address this point, xxx is also including a more in-depth response, as part of this letter to the original 483 observations.   xxx takes seriously its responsibilities in providing a quality product to the public. It continues to be xxx objective to operate in accordance with current regulations as stipulated by the US FDA. We value your communication and commit to meeting current GMP requirements. To this end, xxx has executed xxx critically important actions:

17. W.L. Observation   During the inspection, our investigators observed and documented xxx conditions. An analysis of your xxx collected during the inspection found significant xxx contamination. Response   In conjunction with the conditions noted, xxx has initiated the following:   xxx   Implementation and maintenance of a clean and compliant environment has been executed as detailed previously but includes the following highlights:   xxx   Pursuant to the situation as outlined by the FDA testing of the xxx, xxx initiated a recall of the lot in xxx.   The investigation into the situation that caused this incident indicated the following highlights:   xxx   Root Cause of the Situation:   xxx     Action Plan   As applicable… Due Date    

18. Beyond the Context of the Direct Observations A systemic response to any audit observations must equate to a systemic resolution to any issues within the firm. This action requires further evaluation than just actions in a system at a company site. The FDA in particular will require that all company sites implement corrective actions along the same plan of action. Failure to do so may result in further regulatory actions. Programs need to be established which require any observations and the responses to be circulated for evaluation within a company to determine if other areas are non-compliant.

19. Be Sure to Visit Us On-Line or Call… Our website is filled with lots of tips and guidance on FDA 483’s, Warning Letters and more. Visit us at: www.Compliance-Insight.com You can easily contact us for more help in dealing with FDA Warning Letters by calling us at 513-860-3512

20. www.Compliance-Insight.com Call us at 513-860-3512 Email us at [email protected] Questions? Comments? We are happy to help you!