Understand What FDA Officials Need to KnowSuccessful dispute resolution requires companies to fully understand the roles and responsibilities of each FDA functional
unit and provide appropriate information to officials at each stage of the process. While some companies have expressed frustration
about the multilevel review process, which can seem overly bureaucratic, their frustration often results from not understanding
the agency’s processes.
Companies should provide FDA decision makers with the same data and information that was used by company experts to reach
their conclusions. When company experts effectively communicate with FDA's scientific and technical experts, most issues can
be resolved on their scientific merits. For issues that involve interpretations of GMPs, companies must be prepared to present
their position to the appropriate decision makers at the local district office, the appropriate level in the center, OE, OGC,
The review of the significance of FDA-483 observations begins with a first line supervisor in the FDA district office who
reviews the findings and recommends a response. If the supervisor concludes that the observations do not warrant further regulatory
action, the inspection is classified as "no-action indicated" (NAI) or "voluntary action indicated" (VAI).
If the supervisor classifies the inspection as "official action indicated" (OAI), then the supervisor's recommendation is
forwarded to a district compliance officer who reviews the Establishment Inspection Report (EIR) to determine whether the
inspection findings warrant regulatory action. If the compliance officer concludes that regulatory action is indicated, a
recommendation is forwarded to the district director for approval. Depending on the nature of the recommended action (for
example, seizure, injunction, or warning letter), the regulatory case file may be forwarded to an Office of Compliance at
the appropriate center. At the center level, reviewers confirm that the evidence submitted supports the proposed regulatory
action according to established policies. Then, the case is forwarded through OE and OGC and eventually to DOJ.
There are three principal strategies for resolving issues pertaining to FDA-483 observations:
- assert that the FDA-483 observations were incorrect or their significance is minimal
- demonstrate that the company has implemented effective global corrective actions and controls to prevent and detect such occurrences
in the future
- recall any products that may not meet quality attributes, such as sterility or stability.
FDA is reluctant to initiate regulatory sanctions when it believes the company is acting in good faith to affect corrective
actions in a timely manner — unless there is an immediate health hazard. Therefore, companies can usually avoid regulatory
sanctions by documenting corrective actions for FDA reviewers at each level.
Choose Knowledgeable Staff to Represent the CompanyIt is important that the company utilize personnel who are well versed in FDA practices. If the company staff have limited
experience dealing with FDA, it may be prudent to seek outside assistance from persons who have either worked for the agency
previously or have considerable first-hand experience. Such persons can assist in presenting relevant information to the appropriate
agency personnel to convince them the company has a valid basis for their position and presenting the right information to
the right person at the right time during the review process.
Deciding who will represent the company is almost as important as what is presented. Obviously, anyone presenting information
or data to FDA must be knowledgeable about the issues to be discussed and must be capable of effective communications. Different
qualifications and skills are needed depending upon the purpose of the meeting and the level of FDA attendees. Generally,
the company sets the agenda for the FDA meeting. If FDA asked for the meeting, the company should be represented by those
best suited to address any of the outstanding issues under discussion. The company should anticipate that FDA may need information
for a relatively broad spectrum of topics. Consequently, company representatives should include senior management (chief executive
officer, president, or vice president), technical and regulatory staff (QA/QC director and heads of production or laboratories),
and possibly a company attorney.
Whether to involve company attorneys must be decided on a case-by-case basis. In some meetings (such as a review of scientific
issues or GMP issues) the presence of a company attorney may discourage FDA from engaging in free and open dialogue. If the
company decides that an attorney should be present, FDA may decide to have an OCC attorney represent FDA. Companies must judge
when to introduce their attorneys: too soon may inhibit dialogue and too late may make it difficult to undo damage.
For situations where potential regulatory sanctions are likely, companies may need to seek outside legal counsel to assist
the company's internal legal staff. Outside counsel who specialize in FDA law frequently have first-hand experience interacting
with FDA officials at the various agency levels and negotiating voluntary actions in lieu of litigation.
Companies facing potential litigation also may choose to utilize outside consultants to attend FDA meetings or present written
opinions about scientific or technical issues. Companies are free to choose their own consultants, but FDA may question or
challenge the qualifications of consultants when their background does not match the issues being addressed. Companies should
scrutinize the education, training, and experience of any consultant and verify they have helped resolve similar issues in