Resolving Scientific and Technical Disputes - - BioPharm International


Resolving Scientific and Technical Disputes

BioPharm International

Companies also should carefully manage the roles and responsibilities of consultants during FDA meetings. Generally, responsible management should lead the discussions, answer questions, and make commitments on behalf of the company. Consultants are most effective when there is a disputed scientific or technical issue. Consultants may prepare white papers or technical reports that help identify the issue, and the results of their independent evaluation may be provided to FDA. Consultants who are experts in a particular field may be called upon to provide opinions about a particular study or situation, but their role during FDA meetings should be narrow in scope. Management should not use a consultant as the company's spokesperson because FDA expects company management to be knowledgeable and in control of the situation.

Decide What Information to DiscloseWhen FDA contemplates regulatory sanctions (or has already made an adverse ruling or decision), the company must decide how much information to share. On one hand, companies should provide any information that may dissuade FDA from invoking regulatory sanctions. On the other hand, no company wants to divulge information that may be used against it in civil or criminal proceedings by the agency or in civil lawsuits. Consequently, companies face a constant dilemma between providing too much or too little information.

In most cases, the company can solicit from FDA the nature and type of information that is needed. Different types of information are appropriate for different types of disputes and at different stages of the review process.

Scientific and Technical Reviews. If an FDA reviewer is evaluating scientific or technical data, it is advisable to simply ask the reviewer what additional information or data would be helpful to them and, to the extent practical, provide all information or data that is relevant. Include all pertinent data even if some of it is less than perfect. FDA does not expect perfection, but companies are expected to document that they deal with issues in a responsible manner using sound science.

GMP Reviews. GMP reviews focus on the facts of the case and the significance of the findings. When FDA reviewers at the district office (supervisors and compliance officers) are evaluating the significance of FDA-483 observations, it is particularly important to maintain contact with the reviewers, ensuring they have all the information they need. By opening up dialogue with the local district staff, companies can learn of reviewers' concerns and provide additional information before the matter is elevated to the center level.

To support regulatory actions, FDA-483 observations must be factually correct and supported with records or first-hand observations by FDA officials. If the company has information that shows the FDA-483 observations are incorrect or misleading in any way, FDA reviewers must be given complete information to refute the observation. In this case, the company should respectfully advise FDA that the observation is incorrect and provide supporting evidence.

FDA's evaluation of the significance of FDA-483 observations follows a review process that is elevated up the chain of command from the local district to the center and eventually through the OE to the OGC. Throughout this process, the inspection findings are reviewed to verify that they warrant regulatory action. FDA utilizes it own internal "National Experts" as well as outside experts to provide independent confirmation that the conditions do not conform to cGMPs. Companies disputing FDA-483 observations or trying to convince FDA that the conditions do not warrant regulatory action also should consider obtaining an objective review by independent experts. Independent review is valuable because it affords management a set of "outside eyes," and if FDA reviewers know the outside expert to be credible, their opinions or recommendations may carry a lot of weight.

Management Review at Local Districts. Each FDA unit has its own procedures for elevating recommendations for approval. At the district level, cases are elevated to the director of the Compliance Branch or the district director. At this stage, senior management of the company should discuss their commitment to complying with the laws and regulations with the senior FDA management. They should demonstrate that global corrective actions have been initiated and, where appropriate, provide timetables for completion. Management should promise to keep FDA informed of progress, including periodic reports if corrections will span months or years. Finally, to satisfy FDA concerns, management should demonstrate that its actions are timely and sufficient. Successful discussions may convince district officials that regulatory action is not warranted.

Policy Reviews at Headquarters. Each headquarters (ORA, CDER, CBER, CVM) reviews recommendations from lower level offices. The nature of review varies with each office, but in general, the reviews ensure that the proposed regulatory sanction or administrative decision was made in accordance with established practices and policies and evidence supports the charges. Each headquarters decides whether to forward the case to the OE or OGC. The review at headquarters confirms that the recommendations follow established policies such as Compliance Policy Guides (CPGs), Regulatory Procedures Manual, and others.

Once a regulatory case or administrative matter has been elevated to the center level, there is a high probability that the regulatory action will be forwarded beyond FDA. At this stage of the process, it is vital to offer new and compelling information to headquarters officials to convince them that regulatory sanctions either are not supportable or are not warranted based on accomplished or planned corrective actions.

Generally, but not always, by the time cases are referred to headquarters, the facts and supporting evidence have been pretty well established. Therefore, discussions at this level generally do not focus on the particulars of FDA-483 observations (unless the company has been unsuccessful in resolving disputes at the district level). Such discussions are normally between senior management of the company and FDA. During such meetings, company officials must be knowledgeable about the nature and extent of corrective actions and should be able to make commitments on behalf of the company.

If the meeting goes well, a favorable outcome is possible, but if management has not prepared adequately or is unable to change the views of FDA management, the meeting will not only have had an unfavorable outcome, but might even be held against the company in the form of a prior warning.

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