STATEMENT BY
LINDA A. SUYDAM, D.P.A.
SENIOR ASSOCIATE COMMISSIONER
FOOD AND DRUG ADMINISTRATION
DEPARTMENT OF HEALTH AND HUMAN SERVICES
BEFORE THE
COMMITTEE ON GOVERNMENT REFORM
U.S. HOUSE OF REPRESENTATIVES
JUNE 14, 2000
Introduction
Mr. Chairman and Members of the Committee, I am Linda A. Suydam, Senior Associate Commissioner, of the Food and Drug Administration (FDA or the Agency). I am pleased to have the opportunity to be here before the Committee today to discuss with you FDA's advisory committees. As I will discuss, FDA has made a strong commitment, and given high priority, to selecting the most qualified clinical and scientific experts for its advisory committees and to rigorously complying with the statutes and regulations governing these advisory committees.
FDA is a science-based regulatory agency with responsibility for regulating approximately 25 percent of the gross national product. FDA's mission is to protect and promote the public health by promptly and efficiently reviewing clinical research and taking appropriate action on the marketing of regulated products in a timely manner. FDA oversees foods, drugs, biologics, and medical devices that the American public uses every day.
To carry out that mission, FDA's decisions need to be based on the highest clinical and scientific standards. As science becomes more specialized, it becomes more difficult for general scientists and medical personnel to keep up with the scientific advances in the many areas that FDA regulates. To provide this critical science base, FDA has over 1500 outside experts who provide FDA with essential expertise in highly specialized areas. Many of these experts serve as members on, or consultants to, FDA advisory committees.
Federal Advisory Committee Act (FACA)
The Federal Advisory Committee Act (FACA)(5 U.S.C. App. II) sets forth standards and procedures to govern the establishment, operations, and administration of advisory committees. As defined in FACA, a public advisory committee is any committee, board, commission, council, conference, panel, task force, or other similar group, or any subcommittee or other subgroup thereof, established or utilized by a department or agency of the Federal Government in the interest of obtaining advice or recommendations, and that is not composed wholly of full-time officers or employees of the Federal Government.
The General Services Administration (GSA) has oversight in the management and control of all Federal advisory committees under their Federal Advisory Committee Management regulations in 41 CFR Subpart 101-6.10. FDA's implementing regulations under FACA are found at 21 CFR Part 14. FDA carefully follows the process established under these regulations. The Department of Health and Human Services (DHHS or Department), in concert with GSA, sets policy for components of DHHS with advisory committees, such as FDA, the Centers for Disease Control and Prevention, the National Institutes of Health, and the Substance Abuse and Mental Health Services Administration.
Currently, FDA is administratively responsible for a total of 32 advisory committees, which operate within the legal framework noted above. Each advisory committee has a core membership identified within each committee's charter. The charters for the committees are in existence for a two-year period unless the duration is otherwise provided by law. The authorized core is developed based on the complexity of the issues to be considered and assessment of the issues by the Agency as to the degree of expertise needed. The charters are standardized and formally developed in accordance with the requirements of section 9 of FACA.
Impact of the Food and Drug Administration Modernization Act (FDAMA) of 1997
Section 120 of FDAMA (P.L. 105-115) mandated additional requirements applicable to some FDA advisory committees. The requirements in section 120 provide that FDA may not grant a waiver for an advisory committee member to review his or her own work; there must be at least two members on the advisory committee who are knowledgeable about the disease that the product is intended to treat; and advisory committee members shall be trained in the committee meeting process.
What Does an Advisory Committee Do?
The FDA Advisory Committee system was established:
Advisory committees review many issues, including cutting edge technology, safety and efficacy issues, adverse event problems, labeling issues, guidance documents and peer review of intramural research.
Advisory committees also advise the Agency on general criteria for evaluation, of broad regulatory and scientific issues that are not related to a specific product. Committee members, who have voting status, vote on substantive scientific or policy matters, which impact on FDA's regulatory role. It is very important to note, however, that advisory committee recommendations are not binding. The Agency retains all final decision making authority.
Who Comprises the Membership of an Advisory Committee?
The standing membership of advisory committees includes academicians, clinicians, consumers, and in some instances industry representatives and patients and/or patient care-givers. In addition to the standing membership, temporary voting members and consultants, who may provide needed expertise, may be appointed to participate in an individual advisory committee meeting. FACA requires that committee membership be fairly balanced in terms of the points of view represented to perform the committee's functions. DHHS policy requires that the committee's membership be composed of as equitable a geographic area and ethnic and gender representation as possible so long as the effectiveness of the committee is not impaired. Members should also be selected without discrimination on the basis of race, gender, sexual orientation, HIV status, and cultural, religious, socioeconomic or physical status.
Who Can Recommend a Prospective Member?
In order to recruit new members for its advisory committees, FDA publishes announcements at least once per year in the Federal Register soliciting nominations for current or upcoming vacancies on its advisory committees. All nominations in response to the Federal Register notice must be submitted to the appropriate Center, Office or Division specified in the notice.
Each FDA Center is responsible for identifying and seeking prospective candidates from additional individuals and organizations. The responsible office seeks nominations and referrals from FDA's stakeholders including former and current advisory committee members, FDA scientists, professional societies and journals, academic institutions, consumer groups, patient advocacy groups, self-nominations, and industry.
Selection Process
In screening nominations for prospective standing committee members for scientific and technical expertise and competence, FDA has a thorough, and consistently applied, process. This ensures that we obtain qualified members who are able to provide the Agency advice. The Policy and Guidance Handbook for FDA Advisory Committees states that:
Nominations received are referred to the executive secretary of the appropriate advisory committee who makes the first cut and then forwards the information to the appropriate product review office for consideration. Selection of nominees is based upon: the areas of expertise presently required on the committee; the qualifications of the applicants; potential conflicts of interest; and the need for fair balance. FACA requires advisory committee membership to be fairly balanced in the points of view, and the Agency is committed to diligent pursuit of ethnic, gender, and geographic diversity. For the consumer representative, recruitment efforts are made through FDA's Consumer Consortium, which is a body composed of members of leading consumer organizations. Consumer representatives must be technically and scientifically qualified in the appropriate field and must represent the consumer interests.
For the industry representative, FDA compiles a list of nominees from responses to the Federal Register notice, self-nominations, previous members, and other sources. The list is then sent to all organizations who nominated individuals with the instructions that they should select a representative candidate.
Once the selection process is completed within the Center a formal package containing the list of candidates and their background information is prepared by the Center, signed by the Center Director and forwarded to the Senior Associate Commissioner. The Senior Associate Commissioner appoints all advisory committee members. Each candidate is invited to serve for a set term of office. The candidate is provided an "Acknowledgement of Invitation" to return to FDA either accepting or rejecting the appointment. Most "standing" members become Special Government Employees (SGEs) and are subject to conflict of interest screening. The appointment process is handled uniformly Agency wide.
Temporary Voting Members
If permitted by a committee's charter, the committee's standing voting membership may be supplemented by the appointment of temporary voting members (TVMs) drawn from the present members of other FDA committees as well as from SGE consultants to FDA. Consultants with specialized expertise appointed as SGEs may be granted voting privileges for a particular advisory committee meeting. Such temporary appointments cover a single meeting only and all appointments are subject to the same conflict of interest review as any standing member of an advisory committee. The Commissioner or her designee may appoint temporary voting members to a committee when expertise is required that is not available among the current voting standing members of the committee or to make up a quorum when, because of unforeseen circumstances, a quorum is or will be lacking.
Unless otherwise established in the charter of the committee, a quorum shall consist of a majority of the committee's authorized membership, including TVMs. An advisory committee's charter allows FDA in certain cases to specify a quorum that is less than a majority of the current voting members. For example the VRBPAC Charter states:
Because of the size of the committee and the variety in the types of issues that it will consider, FDA may, in connection with a particular committee meeting, specify a quorum that is less than a majority of the current voting members.
The Agency's regulations authorize committee charters to specify quorum requirements (21 CFR 14.22 (d)).
The need for the Agency to ensure that a meeting takes place is critical to its role as a regulatory Agency. Without the ability to hold scheduled advisory committee meetings, products could be delayed in getting to market.
Terms of Advisory Committee Members
It is DHHS policy to avoid excessive individual service on advisory committees and multiple committee memberships. Specifically, this policy provides that a Federal advisory committee member will not:
If any of the above criteria apply to a candidate's appointment/reappointment, an Exception to Department Policy must be prepared to waive the appropriate criteria(ion). All Exceptions to Department Policy, i.e., appointment waivers, must be approved by the FDA Senior Associate Commissioner and is part of the official nomination process. In concert with DHHS, a strong justification to waive the criteria to avoid excessive service is required.
Potential for Conflict of Interest
While FDA has a great need for outside scientific advice, it is critical that the advice be free from conflict of interest and potential bias. If the advice FDA receives is biased or is perceived as biased, it is of little value to the Agency and only diminishes the credibility of Agency decisions. The outside experts who serve FDA are often pre-eminent scientists in their field such as Stan Prusiner, M.D., recipient of the Nobel Prize, and Douglas Norman, M.D., past president of the American Society for Transplantation. They are typically active researchers on the cutting edge of science. As such, they and their organizations are often sought out by regulated industry to assist in product development. Indeed, studies have shown that academic biomedical research in the United States increasingly is supported by industry. For that reason, outside experts and the research centers where they work, frequently have research grants from and contracts with regulated industry. Thus, most active researchers in the private sector have some ongoing or past relationship with regulated industry. This, by itself, does not preclude them from serving as SGEs. If this were the case, FDA would not get the top scientists in the field and the recommendations of the advisory committees would not be of the highest scientific nature, with a likely impact on public health.
Conflict of Interest Rule
Federal statute and the implementing regulations contain conflict of interest standards applicable to all Federal employees, including SGEs serving on advisory committees. Regulations issued by the Office of Government Ethics (OGE) and DHHS create additional standards of ethical conduct and provide interpretive guidance concerning the Federal conflict of interest statutes. The Designated Agency Ethics Official (DAEO) of DHHS has been designated by the Secretary of DHHS to coordinate and manage the DHHS' ethics program. The DAEO and the DAEO's staff in the Office of the General Counsel (OGC)/Ethics Division provide legal guidance concerning the Federal conflict of interest statutes and regulations and provide guidance, as needed, regarding the application of those legal authorities in specific cases. The DAEO has delegated to the FDA Deputy Ethics Counselor and the FDA Ethics Staff the authority to perform many of the functions of administering the FDA ethics program.
Within FDA, the Commissioner of Food and Drugs has the final authority, to make determinations in conflict of interest matters such as the issuing of conflict of interest waivers, where Federal law accords the Agency authority to exercise discretion regarding an employee's participation in official matters.
Criminal Conflict of Interest Statute (Title 18 U.S.C. 208)
For years, the Federal Government has balanced the need for outside expertise in advisory committees with the need to protect against potential conflicts of interest. A Federal employee, which includes all SGEs, is prohibited from participating personally and substantially in an official capacity in any particular matter in which he has a financial interest if the particular matter will have a direct and predictable effect on that interest (18 U.S.C. 208(a)). The interests of the spouse, minor child, and employer are imputed to the employee. In addition, the interests of the general partner, organization in which he is serving as an officer, director, trustee, general partner or employee or any person or organization with whom he is negotiating or has any arrangement concerning prospective employment are also imputed.
Assessing Conflict of Interest Concerns - The Form 3410
Prior to each FDA Advisory Committee meeting an SGE must complete an FDA Form 3410 - "Conflict of Interest Disclosure Report for SGEs." The Form 3410 relates and is accompanied by a list of sponsors, affected firms, competitors, parent firms, and other information, for each topic to be covered at the upcoming meeting. Financial interest is defined in the regulations as the potential for gain or loss as a result of government action on the particular matter (18 U.S.C.208 and 5 CFR part 2640). The types of interests screened are stocks and investments, primary employment, consultant work, contracts, patents, grants, trademarks, expert witness activities, speaking engagements, and other information.
Steps for Conflict of Interest Clearance
The process for determining the eligibility of outside experts (which can include standing members, TVMs, and consultants) to participate in advisory committee meetings is a labor-intensive task that involves multiple levels of review.
The agenda of the advisory committee meeting or individual assignment (such as consultants providing expertise but not voting) is reviewed to assess the types of matters to be addressed. This assessment is critical because the eligibility and waiver rules vary depending on the type of meeting or assignment (5 CFR part 2640). In considering an assignment for an SGE for a meeting related to a product approval, entities with a financial interest may include the sponsor and firms who will manufacture or market the product being reviewed, products that would be used in manufacture or market conjunction with the one being reviewed, and products that would compete with the one being reviewed.
FDA staff reviews the responses to the confidential financial disclosure questionnaire (Form FDA 3410) and focus on whether a conflict of interest exists. Based solely on the reported information it is often possible to determine that: there is no conflict of interest; there is a conflict of interest and a waiver can be justified; or there is a conflict of interest that is so great, recusal is the only course of action. When clarification is needed, FDA staff may ask the SGE to respond to additional questions.
Advisory committee meetings are scheduled to provide advice to the FDA official making the regulatory decision on products. Typically, the FDA official is an Office or Division Director. The official is notified of any significant conflicts of interest that are reported to enable a determination of the extent to which the member's expertise is important to the meeting. If the reported interest is significant and the need for the member's services is not great, recusal is appropriate. If the member's services are important to the meeting because nobody else with the expertise can be obtained for the meeting, a waiver may be appropriate. In making this determination, the review office and division take into account the requirements of FDAMA.
FDA's Ethics staff conducts an independent review of all conflict of interest waivers and makes a recommendation to the Senior Associate Commissioner concerning the waiver. If questions arise about the justification for the waiver, the Ethics staff may ask the recommending office for additional information. The Ethics staff may also consult with the OGC in DHHS or OGE.
A proposed waiver and justification for the waiver will have received eight levels of review before reaching the Senior Associate Commissioner for final approval. As the final step, the appointing official makes the decision based on the information provided. The conflict of interest determination may indicate that: no action is needed; a waiver to participate as a full voting member is granted; a waiver to participate with nonvoting status is granted; an appearance authorization is granted; or the SGE is excluded from participating in the meeting.
What is an appearance determination (502) and who gets one?
The OGE "Standards of Ethical Conduct" for employees of the Executive Branch provide criteria by which to judge the appearance of lack of impartiality where actual conflicts of interest, as defined by 18 U.S.C. 208, do not exist. Federal regulations, 5 CFR 2635.502, provide a procedure for "waiving" certain appearance problems. Similarly, even where 5 CFR 2635.502 is not technically applicable, FDA may decide to reassign a matter when there is a concern about appearances.
Waivers
In the 1990s the Institute of Medicine (IOM) recommended to FDA that it formulate a written guidance for granting waivers. An FDA Taskforce, in collaboration with the DHHS Ethics Division, created the "Waiver Criteria Document" (WCD). In 1997, the OGE audited the FDA Ethics Program, including the Advisory Committee Program, and concluded that it was ". . . impressed with FDA's program for protecting SGEs from conflict of interest" and that it was ". . .a model for other Agencies to use in developing their own systems and procedures. . ." The WCD is an evolving document which provides guidance for FDA staff, Advisory Committee Members and other SGEs about the Agency's policies and procedures for handling conflicts of interest. The WCD 2000 describes changes to the original document, including an updated format, revisions to existing categories, and the creation of new categories to clarify waiver criteria practices that have been in existence for some time. The concepts and underlying principles of the WCD remain unchanged.
FDA has authority to allow an advisory committee member (standing and temporary) to participate in the review of a new therapy even if there is a potential conflict of interest, as long as FDA complies with applicable legal standards. FDA may provide for this participation by granting a waiver under 18 U.S.C. 208 for the SGE.
Whether a waiver should be sought or granted is subject to scrutiny and review by more than eight different parties, which include:
These seven evaluations occur before the final evaluation by the deciding official in FDA, the Senior Associate Commissioner. In some situations, legal counsel at DHHS and OGE also may be consulted prior to a decision. At any level of review a waiver can be removed from consideration and the SGE excluded from participation. This review allows for an in-depth assessment of the waiver request.
Who is Granted a 208(b)(3) waiver?
Under section 18 U.S.C. 208(b)(3), an SGE, who may be a standing or temporary member, may participate in an advisory committee meeting despite a potential conflict of interest. After reviewing the SGE's financial disclosure statements, the Senior Associate Commissioner may determine that the need for the employee's services outweighs the potential conflict of interest created by the financial interest involved. A waiver may be indicated if, for example, the SGE will provide expertise that is necessary to the issues on the agenda that would otherwise be considered unavailable. Another example would be if the product in question is widely studied, it would be difficult to find a qualified SGE who was not at least involved, either personally, or indirectly through his or her institution, with that product or a competing product. After a review of the reported interests, the Senior Associate Commissioner either certifies in writing that the need for the individual's services outweighs the potential conflict of interest created by the financial interest involved or denies the waiver.
Vaccines and Related Biological Products Advisory Committee (VRBPAC)
One of FDA's advisory committees of particular interest to the Committee is the VRBPAC. The VRBPAC is composed primarily of non-government experts in fields related to vaccines, such as infectious diseases, immunology, virology, bacteriology, molecular biology, pediatrics, and biostatistics. The last selection for committee vacancies occurred in September 1998. Fifty-seven candidates were reviewed for five slots. While VRBPAC provides advisory opinions to FDA on a wide range of vaccine-related issues it does not specifically recommend for or against licensure of a vaccine. VRBPAC provides recommendations on the adequacy of safety and efficacy data. FDA is not required to follow the recommendations of advisory committees, but often does. In addition, FDA has no mandate to present all vaccine products before the committee prior to licensure. There have been a few instances where a vaccine has been approved without VRBPAC review.
The committee's role is to provide recommendations on safety and efficacy, but these are not the sole issues considered by the Agency in approving a product. There have been instances when VRBPAC unanimously voted that the data presented was adequate to support the safety and effectiveness of the product, however, FDA delayed approval of the vaccine until all product manufacturing issues were resolved.
Conclusion
Mr. Chairman, let me assure you that the Agency has made every effort to rigorously comply with the applicable statutes and regulations in appointing outside experts to the FDA Advisory Committees. Multiple, independent and sometimes redundant reviews, taken together, ensure FDA, the medical community, industry, consumer and patient groups and the American public that advisory committee recommendations are based on the best possible science and are free from bias.
Thank you, and I would be happy to answer any questions.
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