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:
1. to provide independent expertise
and technical assistance
related to the development and
evaluation of products
regulated by FDA;
2. to lend credibility to the
product review process;
3. to speed the review of products
by providing a visible
sharing of the responsibility
for evaluation and judgment;
4. to provide a forum for public
discussion on matters of
significant public interest;
5. to allow sponsors and consumers
to stay current with trends
in the product development and
review process and changes
in regulations and guidelines
related to FDA-regulated
industries; and
6. to provide external review
of FDA intramural research
programs.
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:
- Candidates should be carefully screened to ensure that
they possess expertise relevant to the particular subject
matter on which their advice will be sought.
- Attention also should be paid to reputation and leadership
qualities.
- Whenever possible, nominees should be acknowledged experts
in their fields whose credibility is beyond question.
- All nominees should have both demonstrated skills in the
critical evaluation of data and, to the extent feasible,
the communications skills necessary to promote efficient
and effective committee deliberation.
- The responsible office is expected to seek diligently,
and document external evaluation of, the credentials of
the nominee.
- The process of obtaining external evaluation and endorsement
is essential.
- Appropriate sources of external evaluation include current
advisory committee members, senior officials in the individual’s
primary institution, and relevant professional society boards.
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:
- serve continuously as a member of any single advisory
committee for more than four years;
- serve for more than eight combined years within a period
of 12 years on one or more committees within an agency;
- serve on more than one committee within an agency at the
same time; or,
- serve on the same committee at the same time with another
individual who is affiliated with a particular non-Federal
organization or institution in the same city.
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 levelsof 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:
- the Committee Members;
- the Executive Secretary;
- the Committee Management Specialist;
- the Program Officer;
- the Chief of Scientific Advisers and Consultants Staff;
- the Ethics Specialist;
- the Director of Advisory Committee Oversight; and,
- the Senior Associate Commissioner.
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.
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