Legal Reviews. Throughout the FDA review process at both the district and headquarters level, the particulars of the case are reviewed from a legal perspective to make sure evidence is available to support the charges. However, the formal review by FDA lawyers does not occur until a case is forwarded to the OGC. In most instances, OGC review is the last step in the review process. In the case of warning letters, OGC approves or rejects recommendations from the local districts or centers. For civil and criminal sanctions, OGC lawyers forward approved recommendations to the DOJ.

At the OGC stage of the review the company should use company lawyers or outside counsel to communicate with OGC lawyers. While other senior management may participate in the discussions with OGC, company lawyers will need to address the legal matters with the OGC lawyers. The discussions should focus on determining FDA's legal course, presenting additional information or data to negate some or all of the charges, or voluntarily committing to corrective actions that obviate the need for litigation.

Companies may invoke attorney-client privilege to protect information related to disputed issues from disclosure to the FDA (or during civil litigation, such as lawsuits by shareholders or patients). If so, the company must decide how to use any information reported under privilege during FDA's dispute resolution process. Companies must decide whether or not to waive attorney-client privilege if the agency requests protected information. They must consider the benefits to be gained from voluntary disclosures against the risk of an unfavorable ruling by FDA.

Requests for FDA meetings should clearly state the reason for the meeting, outlining specific objectives and listing the names and titles of company representatives (including consultants). If the company desires certain FDA officials to be present, the request should include this information. The company should avoid the temptation to introduce issues not identified in the meeting request. For meetings requested by a company, FDA usually allows the company to set the agenda. The company should allocate enough time to address each of the meeting’s objectives. The agenda should clearly identify the issues to be addressed, as well as pertinent background information. It is important to confirm that the company's understanding of the issue is correct. Once the issue is agreed upon, the company should present its rationale and the support for its position.

During the formal presentations and the subsequent discussions, management should judge the effectiveness of the discussions and listen for signals or messages that are being delivered by FDA. Frequently FDA officials will not come right out and say they disagree with the materials presented; silence or no comment should not be interpreted as agreement. Companies may leave meetings believing they were successful because FDA did not object, while FDA officials may leave the same meeting with the impression that management "does not get it." Therefore, before the meeting is completed, management should elicit from FDA a response to the issue.

Rather than soliciting open-ended questions and comments, it is usually advisable to restate the company's conclusion and then ask FDA attendees if they agree. This should keep FDA responses directed at the specific issues of concern to the company. It also is prudent to ask FDA attendees if they have any other concerns that have not been communicated to the company.

Finally, at any FDA meeting to discuss disputed issues, it is vital that company representatives remain controlled and professional at all times. Showing frustration or open hostility will never help the company's position, and may damage its credibility. If the company still disagrees with FDA's position (after the presentation and discussions), the company should end the meeting by restating its conclusions in a deliberate manner with the supporting rationale. Meetings do not always conclude with a resolution of the disputed issue, but no meeting should finish until everyone agrees that they have a common understanding about what remains unresolved. If possible, both parties should agree upon the next steps to reach a resolution.

Establish Credibility with FDANo dispute can be successfully resolved unless the company establishes credibility with FDA officials. Building credibility takes considerable effort and will not happen overnight. The company must communicate early, often, and effectively. FDA expects companies to respond to the issue and to understand FDA's position. Empathizing with FDA's position does not mean agreeing with FDA's position, but understanding why FDA is concerned. Credibility means being accountable for the actions of the company and not making excuses. One common mistake made by management is offending FDA reviewers by making excuses such as saying the issue was the fault of someone else or "that’s never happened before."

Credibility also means demonstrating integrity by always providing FDA with information that is truthful, accurate, and complete. FDA expects all communications to exhibit these qualities. Credibility means making commitments to achieve timely corrective actions, showing reasonable progress against a planned schedule, and notifying FDA in advance when schedules cannot be met. Credibility means learning from the experiences of the company and others in industry by not having recurring issues that could have been prevented. Credibility also means boasting loudly and proudly about correcting issues and implementing global improvements. Credibility means having the confidence to disagree with FDA when the company believes it has a valid position and is capable of presenting its rationale and support in a professional manner. Finally, credibility is established when the actions and decisions of the company clearly show a commitment to complying with cGMPs and FDA sees positive progress.

ConclusionThere are now new and improved opportunities for dealing with FDA-483 obserations and other disuputes that arise from FDA inspections. However, until the agency receives comments and finalizes the draft guidance published in August 2003, companies will still need to deal with disputes according to established FDA procedures and practices.

Successful dispute resolution begins by following the applicable regulations, policies, procedures, and guidance documents that define the agency's process for handling disagreements about scientific and technical issues. Companies that do not understand and follow the prescribed process for disputes can not expect to have a favorable outcome. Companies, even if they follow the process, will not have a positive outcome if they do not provide the agency with the appropriate information at the right level.

Successful dispute resolution begins with reaching a common understanding of the issue and understanding what information is needed by officials at each level of review. Companies must decide the optimum timing of FDA meetings and who will represent the company. Knowledgeable management must be aware of the issues and explain and defend the company’s position in a credible manner. Finally, successful dispute resolution depends on establishing credibility with FDA by being accountable for company actions and demonstrating a commitment to comply with the law and regulations. Credibility is established by making global corrective actions in a timely and reasonable manner and also by giving FDA confidence that the company will perform the right actions at the right time for the right reasons.

References1. FDA. Formal dispute resolution: scientific and technical issues related to pharmaceutical cGMP, draft guidance for industry [draft]. 2003 August. Available from URL: www.fda.gov/cder/guidance/5804dft.htm.