1. 1. A Compliance Officers Guide to Surviving the StormCompliance Insight, Inc. 513-860-3512 Copyrighted 2013
2. 2. What is an FDA Warning LetterThe United States Food and Drug Administration defines a Warning Letter as"...a correspondence that notifies regulated industry about violations thatFDA has documented during its inspections or investigations. Typically, aWarning Letter notifies a responsible individual or firm that the Agencyconsiders one or more products, practices, processes, or other activities to bein violation of the Federal Food, Drug, and Cosmetic Act (the Act), itsimplementing regulations and other federal statutes. Warning Letters shouldonly be issued for violations of regulatory significance, i.e., those that mayactually lead to an enforcement action if the documented violations are notpromptly and adequately corrected. A Warning Letter is one of the Agencysprincipal means of achieving prompt voluntary compliance with the Act.
3. 3. Documents a violation of law or regulation Establishes that a firm or person has beennotified of the violation Your response to the FDA 483 may have beendeficient Designed to promote voluntary compliance Stepping stone to regulatory action
4. 4. What does this letter mean foryou and your firm? Warning Letter is considered to be priornotice Respond within 15 days FDA will initiate necessary action if noresponse is received Time is CRITICAL you have to organize,understand, resolve and respond to the FDA
5. 5. Before we begin on the responsework, let me say a few words about
6. 6. Two Approaches To AssessmentFocusedAssessment Basedspecifically onitems from theWarning LetterOverallSystemicAssessment Look beyondthe specificitems, otherareas/products
7. 7. Writing the ResponseThere are some basic rules that can be establishedregarding writing a response letter. Some or all ofthese rules may apply depending upon the particularsituation of the firm e.g. lengthy list ofobservations, serious issues on the warning letter,etc.
8. 8. Writing the Response1. Someone in a high level in a Quality group (internal or external)should write the response.2. Personnel copied on the response should include high-levelmanagement. This shows that management at the firm is awareof the issues and the commitments being made.3. Include a cover letter or opening statement. Tell the FDA thatyou are serious about resolving the issues. State the siteaddress of the audit and the dates.
9. 9. Writing the Response4. Always remember that you are writing the response to the auditorsmanagement governmental auditing bodies do have supervisors andmanagers. Do not assume that the person reading the reportunderstands the context of the observation or your reply.5. Re-state the observation and reference number in the response.Typically, the observation goes directly above the response.6. If possible, indicate the related compliant systems. This shows that youare in control and that some operations were functioning withinacceptable GMP parameters.
10. 10. Writing the Response7. If the action item is going to take some time to implement, state whatwill be done in the interim to be compliant with GMPs. Dont simplyindicate that actions will be taken in six months to correct the issue inwhich you are currently out of compliance without addressing what youwill do to be compliant from the current date until the corrections areimplemented.8. 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. 11. Writing the Response9. Define how enhancements will prevent recurrence of the issueobserved. Dont assume that the reader will understand this fact.10. Explain what will be done to expand, enhance or streamline thecompliance system.11. Dont forget about training. Allow sufficient time to implementchanges to incorporate training that may include proficiencytesting.
12. 12. Writing the Response12. Describe how the firm will monitor the progress and effectiveness of thecorrective actions.13. It may be helpful to explain that despite the issues noted, there has never beenan issue. It is not advisable to use this response tactic each time but it can beadvantageous for critical observations to state something on the order of theproduct has always met predetermined quality parameters14. Revise, revise, revise. Allow other people not directly involved with the audit toreview and comment on the response. They may have insight on responsewording that would assist in clarification or strengthening of points.
13. 13. How the response should look
14. 14. Indicating corrective actions taken orplannedRestating the observation orcommentsDefining root causeDeveloping the due dateWhen initially formulating a response, a 4-Stage Inspection ResponseApproach may be helpful to develop perceptive on the format of theresponse and contribute to a better understanding of what actually needs tobe implemented to be compliant. This type of approach includesItem1Item2Item3Item4
15. 15. Cover Letter Example this isfrom top level managementWe are in receipt of your communication dated --- on -----. We take yourcommunication very seriously and commit ourselves to address yourconcerns adequately and expeditiously. We will take all the necessarymeasures to ensure our customers well-being and safety. Enclosed pleasefind an attachment that addresses your concerns on an individual and on asystematic basis.We agree that a sound Quality System is the result of effectivemanagement commitment, dedicated employees, and sound processesand practices.To that end we have retained _____, a reputable consulting firm, to assessour Quality System in greater detail and to help ensure that our CorrectiveAction plan will address all systemic issues effectively. We have attached aqualification profile for your review.
16. 16. Response Letter from theresponse teamxx June 20xxU.S. Food and Drug Administrationc/o , Compliance Officer, Re: Warning Letter xxxDear Mr. xxx:This letter provides the response from to the Food and Drug Administrations (FDA) Warning Letter dated xxx(Attachment 1) related to findings from FDAs inspection of xxx facility on xxx through xxx. As the Warning Letter notes, xxxresponded to the FDA Form 483 on xxx (Attachment 2 for the 483 and original response) but notes that it did not provide anydetailed information regarding proposed corrective actions. To address this point, xxx is also including a more in-depth response, aspart 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 inaccordance with current regulations as stipulated by the US FDA. We value your communication and commit to meeting currentGMP requirements. To this end, xxx has executed xxx critically important actions:
17. 17. W.L. ObservationDuring the inspection, our investigators observed and documented xxx conditions. An analysis of your xxxcollected during the inspection found significant xxx contamination.ResponseIn conjunction with the conditions noted, xxx has initiated the following:xxxImplementation and maintenance of a clean and compliant environment has been executed as detailedpreviously but includes the following highlights:xxxPursuant 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:xxxRoot Cause of the Situation:xxxAction PlanAs applicableDue Date
18. 18. Beyond the Context of the DirectObservations A systemic response to any audit observations must equate to asystemic resolution to any issues within the firm. This action requires further evaluation than just actions in asystem at a company site. The FDA in particular will require that all company sites implementcorrective 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 observationsand the responses to be circulated for evaluation within acompany to determine if other areas are non-compliant.
19. 19. Be Sure to Visit Us On-Line or CallOur website is filled with lots of tipsand guidance on FDA 483s, WarningLetters and more. Visit us at:www.Compliance-Insight.comYou can easily contact us for morehelp in dealing with FDA WarningLetters by calling us at 513-860-3512
20. 20. www.Compliance-Insight.comCall us at 513-860-3512Email us atFDAWarningLetterTeam@Compliance-Insight.comQuestions? Comments?We are happy to help you!