Food and Drug Administration Advisory Committee Meetings
To be sure, it is not the fruits of scientific research that elevate a man and enrich his nature, but the urge to understand, the intellectual work, creative or receptive. Albert Einstein
The FDA is not a monolith but a collection of divisions and groups that are run as feudal city-states. Bert Spilker
While this chapter focuses on the Food and Drug Administration (FDA) Advisory Committee meetings there are many aspects of the preceding chapter that relate to this one as well, but which are not repeated. Readers of this chapter are referred to Chapter 88 in addition, to obtain a more complete understanding of FDA Advisory Committee meetings.
DESCRIPTION OF THE MEETING AND ITS ORGANIZATION
The FDA holds about ten to 20 advisory committee meetings each year. Most are held at local hotels within an approximately 15 mile radius of their Maryland headquarters and usually last for two full days. The 32 advisory committees consists of members appointed to a four-year term, plus a nonvoting industry representative, a voting patient advocate representative, statisticians from the FDA or academia, and a Chair. There are usually about 12 to 25 members of the committee. The meeting is videotaped and streamed live to sites around the world and CDRoms, DVDs, and transcripts may be purchased from commercial organizations to understand the dynamics of these meetings.
It is important to note that the role of the advisory committee is just that, “advisory,” and the FDA makes the final decision on approvability of the product being discussed.
BENEFITS AND DISADVANTAGES OF A FOOD AND DRUG ADMINISTRATION ADVISORY COMMITTEE MEETING
Benefits of Presenting at a Food and Drug Administration Advisory Committee Meeting
The company may detect an adversarial stance at the FDA toward their product for a reason they do or do not understand, and the company may believe that the advisory committee, a group primarily composed of academicians (primarily clinicians), would be better disposed toward endorsing the company’s position. If this is considered likely, then the committee’s vote could influence the FDA‘s position on whether to approve the drug. Therefore, the company would want to encourage the FDA to hold an advisory committee meeting to review, discuss, and vote on their application. In some cases, the company may request and be granted a closed advisory committee meeting, but this is very uncommon.
Reasons to Avoid Presenting at a Food and Drug Administration Advisory Committee Meeting
In the opposite situation, a sponsor may not wish to place their drug in the public limelight of an FDA Advisory Committee meeting because the meeting will highlight any shortcomings of their drug, delay its review, and require a great deal of senior staff time to prepare and rehearse for the meeting. Additionally, a negative result could adversely affect the company’s image as well as its stock price. Another issue that sometimes occurs is when a member of the advisory committee is known to have a scientific or medical position on an important issue that is strongly contrary to that of the company. While the company may challenge the fairness of a member or his or her conflicts of interest, these challenges have often been rejected, even in obvious cases of bias by the members on the Committee. An advisory committee may complicate and delay the FDA‘s review process, and the advisory committee deliberations may have a major, unintended effect on the company or the drug’s future.
Requesting that a Food and Drug Administration Advisory Committee Meeting Be Held or Avoided
In most cases, a company has little influence on the FDA‘s decision to either schedule or to omit an advisory committee meeting to discuss a new New Drug Application. On the other hand, there are occasions when a company can lobby to dispense with such a meeting or to have one when it is not planned, and there is precedent when each of these approaches has been successful.
If it is perceived that the FDA is leaning in one direction or the other, even during early stages of a drug’s development, the company may begin to consider reasons at an early stage why they believe such a meeting might be unnecessary, or alternatively why it might be highly desirable.
Choosing the Most Compelling Reasons to Discuss with the Agency
If a company has decided to try to lobby either for or against a meeting it must gather the reasons that it believes are the most compelling from a scientific and/or medical perspective. These should be brought up at regularly scheduled meetings with the FDA and also in informal company discussions. No more than three reasons should be advanced by a company in their argument because any additional reasons would most likely make all of their arguments appear to have little merit. If a company believes that it has more than three messages to consider, they should choose the three most compelling ones to present.
While this issue could be raised at an FDA meeting attended by functional reviewers (e.g., medical reviewer, toxicology reviewer, pharmacokineticist reviewer), it is preferable to discuss it with the Division Director in attendance, since that person and his or her superior, the Office Director, will have major input on the decision made.
FOOD AND DRUG ADMINISTRATION ADVISORY COMMITTEE MEETING BRIEFING BOOK
The objective of the briefing book for an FDA Advisory Committee is to present the most persuasive case for approving the drug, which means the most compelling data establishing safety, efficacy and a positive benefit to risk balance. Most experienced professionals suggest that the length of this book should be about 20 to 30 pages in length, although they usually are about 100 pages long. Some experts advise that the length of the briefing book should be about what an intelligent expert can read in one to two hours during a plane or train ride. If it is longer, most committee members will not finish their review. If it is too short, then important information will have been left out. The book’s summary should start with the public health message, which is the medical need for a new product to treat a certain group of patients, followed by the medical value of the specific drug being developed in addressing this medical need.
In addition, the sponsor must be open and discuss any problem in the program or data. A display of scientific honesty and integrity shows transparency, which is an important characteristic of any briefing book and at all meetings with a regulatory agency. New issues or data may not be brought up at a meeting that is not present in the briefing book, unless the agency concurs at the time of the meeting. Usually, this practice is appropriate and companies that abridge it annoy the agency. Numerous aspects of how to prepare a briefing book were mentioned in Chapter 87, but the briefing book for an advisory committee meeting is quite different in many ways, and it must seek to persuade the committee members about the value of the drug. One must consider the consequences of every sentence written. For example, what is the evidence to support the sentence? Are all relevant statements referenced? What can be challenged? Is this sentence an opinion or fact? Does this sentence raise additional questions?
In a few cases, the FDA convenes its advisory committees not to review a product’s marketing application, but for advice on guidelines or methodologies during the investigational period and is likely to ask a company to prepare a briefing book focusing on those issues. In that situation, the company’s approach must be more academic, scientifically precise, and responsive to the FDA‘s request.
Every briefing book is an opportunity for the sponsor to present the information it deems appropriate and important. Whereas briefing books during the investigational meetings pose questions and seek answers, those prepared for advisory committees are
not asking questions. When a company presents balanced, complete and transparent information, it shows a positive spirit of seeking a collaborative partnership with the agency. It is critically important not to seek approval of unreasonable goals from the regulatory agency or the committee at this meeting.
not asking questions. When a company presents balanced, complete and transparent information, it shows a positive spirit of seeking a collaborative partnership with the agency. It is critically important not to seek approval of unreasonable goals from the regulatory agency or the committee at this meeting.
PREPARING FOR THE MEETING
Initial Activities
Companies must begin preparations from three to five months in advance of the advisory committee meeting and reserve a group of two- to three-day blocks of time for these preparatory meetings and rehearsals. The person who is put in overall charge of the preparations and presentations should have the authority to make decisions and not be dependent on taking all questions back to the headquarters for a decision or resolution. This person is, therefore, an active participant at all scheduled meetings. He or she will assemble a team to plan and attend this meeting. A good place for this person to start is to list the types of professionals that need participate, and then to discuss with advisors who the best individuals are for each role.
Some of the common roles for the company’s team include:
One or more senior clinicians within the company plus a few investigators with whom the company has built up a strong and positive relationship and who have an excellent reputation in their field
Presenters who have been identified to present and answer questions in their area (this is likely to include some of the professionals mentioned in Point 1)
Statistician(s); a senior company statistician and often a senior well respected academic statistician is invited to participate as a consultant
Regulatory advisors both within the company and one or more consultants who are experienced in assisting companies with FDA Advisory Committee meetings
Audio-visual experts, often from an outside firm (if the group described in Point 6 is asked to lead the overall preparations, it is likely that they will have their own audio-visual staff)
A group of slide experts may be brought into the process, particularly if 500 or more slides are anticipated to be used in the presentations and backup
A preclinical expert or experts is usually involved, but the number and type of professional(s) depends on the issues that are likely to be discussed at the meeting
A public relations or communications professional who will work with the media, financial individuals, and companies and any other external groups such as patient associations (e.g., to obtain a speaker for the public session)
Conference staff to make arrangements with hotels, restaurants and other such venues
Technical computer help
Administrative assistants and secretarial staff to help with a myriad of details
Media trainers (often, technical experts who are adept in their fields need to brush up on their communication skills)
An external group that specializes in leading this type of activity may be asked to participate. These groups help organize and run this process and rehearsals many times each year. Their participation allows busy executives and managers at the company to devote more time to their “day” job rather than being taken away to spend a disproportionate amount of time on this activity.
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