The subcommittee thought that it would be helpful to its deliberations to review the past history of efforts made to strengthen the organization and conduct of scientific research in the FDA and its predecessor agencies. What follows is a synopsis of materials provided from the agency's archives.
The Bureau of Chemistry, established in the Department of Agriculture as the earliest predecessor of the FDA, established a Food Research Laboratory almost at its inception in 1906, underscoring its commitment to the principle of science-based regulation. In subsequent years, many of the Bureau's field laboratories were encouraged to mount research programs in analytical methodologies to improve the quality of their regulatory activities.
In 1955, the Report of the Citizens Advisory Committee (CAC) on the Food and Drug Administration, to the Secretary, DHEW, stated:
Research is the heart of any scientific operation. Although the FDA is primarily a regulatory agency, it must engage in research of the sort that leads to more accurate scientific methods of determining whether a food or drug is safe. Such research in scientific methodology, and perhaps a limited amount of what might be termed 'random research,' can do much to upgrade the professional competence, elevate the morale of the scientific workers, and contribute to the general effectiveness of the FDA.In response, the Agency stated:
FDA agrees with this observation and strives to conduct its operations to encourage a maximum of research activity...consistent with the resources available and the ever-present obligation for day-to-day consumer protection. Due to severely limited funds and facilities, practically all research now conducted is applied research and much of this is a 'brush fire' operation....Adequate accomplishment on this recommendation will not be possible until much larger funds and facilities are made available to the FDA.
The report of a distinguished panel, convened in 1958 as the DHEW Secretary's Consultants on Medical Research and Education, stated:
The Consultants are of the opinion that a vigorous research effort is critically important to the effective performance of the statutory responsibilities of the FDA....One hundred and twenty-two professional scientists are a woefully small group with which to resolve the manifold, complex problems arising in the food, drug and cosmetic areas...
Early in 1959, the Agency established the new position of Scientific Director, with a job description that stated in part:
The Scientific Director is responsible for the effective conduct of scientific research and development of scientific criteria for the... operations.... He is broadly responsible for furnishing leadership and inspiration to scientific personnel... to increase the professional stature and recognition of the FDA as an enforcement activity based squarely on scientific foundations.... The incumbent is the key scientist of the Administration on matters of scientific research and problems.... He develops and plans the objectives and emphasis of scientific research... develops long-range plans... studies and evaluates current research programs and projects on a continuous basis to determine if appropriate standards of performance are being met....
Six months after his appointment the Scientific Director submitted a report to the Commissioner. Some of his observations follow: "On the whole, FDA scientists are fairly well trained and competent, with a strong loyalty and devotion to their work. A few are distinguished. Nevertheless, I have been repeatedly amazed by evidence of scientific 'provincialism'.... If the work of the FDA is to keep abreast of new developments in food and drug science and technology, some infusion of new blood is imperative..." Among his recommendations were: "Affirm a policy to encourage attendance of and participation in scientific meetings... boards and committees of scientific and professional societies... seminars and symposia.... Broaden the base of knowledge and competence in certain areas... by consciously bringing into the (Agency) scientists from universities, foundations and industry... even where this might bypass a currently employed person... (develop a program of) special conferences and seminars within the (Agency)... and weekly intra-and inter-division seminars and research conferences... Arrange for the appointment of (an external) Scientific Advisory Board.... Organize an Institute of Food and Drug Research within the framework of the (FDA).... Earmark a specific research fund from each annual appropriation to be used for basic research in foods, drugs and cosmetics.... Appoint (an intramural) research committee...to assist the scientific director in the planning and coordination of research activities..."
In presenting his proposed revision of the scientific organization of the Agency, the Scientific Director observed that "...when routine analytical control and research work are shared by the same personnel group, the urgency of the enforcement work will often take precedence over the long-range research activities..." After noting that "there are four rather different types of laboratory work done (in the Agency): certification.., analysis.. , analytical method development.., and basic research.., he proposed to separate the basic research function in the new Institute, but to maintain linkages with each of the Agency's Bureaus by forming individual joint research committees containing representatives of the Institute with each Bureau.
Many of the Scientific Director's recommendations appeared to have received verbal endorsement, but they ultimately foundered in bureaucratic opposition and inertia; the Institute proposal in particular was never endorsed.
In 1962 a Second Citizens Advisory Committee (CAC) on the (FDA) was appointed by the Secretary, DHEW. The Report of that group states:
"The Committee believes that an upgrading of the scientific effort of FDA is essential to improving consumer protection. Toward this end, the Committee feels that all scientific functions should be combined in a Food and Drug Institute...(to be) headed by....an eminent scientific administrator. The Institute would be expected to generate an air of scientific inquiry which would attract scientists to it, and to use.. (such mechanisms).. as joint appointments with universities and other scientific organizations, contracts or grants for research projects, improved recruitment of scientific personnel through a special scientific personnel office, improved coordination of scientific effort....and the use of scientific advisory councils for the evaluation of work and the planning of new efforts.
The very first recommendation of the Committee is entitled FDA should increase its scientific efforts to provide greater protection to the consumer regarding foods, and states, among others, that "FDA should exert greater scientific leadership..(and)..The scientific staff should participate in policy decisions." Chapter V of the Report deals explicitly with the creation of a Food and Drug Institute "to strengthen and give greater stature to the scientific and medical work of FDA." Other recommendations in this chapter state: "Positive steps should be taken to improve the conditions of employment for physicians and scientists...Scientists and physicians should have a greater voice in the determination of policies and in the administration of FDA...FDA should strengthen its research program (in) methodology, testing, and related areas in the basic sciences....There is urgent need for closer cooperation of the scientific side of FDA with PHS and NIH..(and)..Closer professional relationships between the scientists and physicians in FDA and their counterparts in industry should be encouraged."
In 1963 FDA established the Bureau of Scientific Research to provide the Agency with an organization that could devote the major portion of its time and talents to the scientific research problems that are associated with the mission requirements of the FDA, and which would at the same time be relatively free from the technical and administrative pressures which are inevitably associated with the responsibilities of a regulatory agency.
In 1965, the Secretary, DHEW ordered an internal study headed by Rufus Miles to review the FDA . The report stated:
It is essential to build a strong bridge between the scientific activities of FDA and the outside community of science. Essential to this is a strengthening of the internal scientific resource. Additional scientific talent should be brought in. FDA scientists should have more opportunities for research, more opportunities to refresh and upgrade their skills. The (FDA) should further strengthen its relationships with the university community.
In 1969 the incoming FDA Commissioner, because of his concerns about the "low scientific credibility" of the Agency, convened The FDA Ad Hoc Science Advisory Committee, headed by Roy Ritts, to review and evaluate the total scientific effort of the Agency and to advise the Commissioner on aspects of FDA's science activities that warrant improvement. Among the Committee's findings were the following: An uneven scientific environment and uneven quality of science; a rich menu of "challenging, fascinating" science, leading to the conclusion that "any reputation the FDA may hold as an unattractive agency for scientists....are related to the FDA itself and not to the intrinsic nature of its scientific responsibilities;" a general morale problem that permeates the scientific environment due to such things as a perception of bias in the power structure of the agency that favors compliance over science, inadequate science planning and managment that does not adequately include the opinions of the scientists themselves, inadequate scientific input to at least "some important regulatory decisions,"and inadequate scientific input to administrative decisions that may have a significant impact on scientific activities; inadequate central science planning and management; and inadequate scientific communication within the Agency and with colleagues in universities and industry.
The Committee produced an extensive list of recommendations, among which were: the appointment of an Associate Commissioner for Science, who would, among other responsibilities, be the "senior spokesman for science in the Agency" and the "principal advisor to the Commissioner on science policy for the FDA;" and that the Commissioner establish a centrally managed system of external peer interaction and review that would include the formation of a National Advisory Council for each Bureau of the Agency, Scientific Review Committees and Ad Hoc Scientific Advisory Committees, and a "major high-level Science Planning Committee."
In its Concluding Statement, the Committee offered a number of observations, among which were the following:
...the Committee perceives that while the FDA is a regulatory agency and must remain so to accomplish its objectives, it can no longer permit the compliance and legalistic attitudes still extant at all levels in management to be the determining factors in the Agency's decrees...The Committee acknowledges that the legal and regulatory benchmarks are to be met, but this must occur only by marshalling a critical scientific resource that regularly permits a rational, consistent and supportable basis for decision-making.....the Committee is convinced that only with a larger and specialized group of scientists developed to meet the current and future needs of the FDA can this critically important regulatory agency address the enormous volume that rightly should receive scrutiny with the new science and technology...(and) ...Even with well-trained and adequate numbers of scientists, the FDA cannot make optimum use of this basic resource without definitive reorientation of the organization in which it functions. The interdigitating aspects of the environment and the management of science must be remedied.
In May, 1991 the Final Report of the Advisory Committee on the Food and Drug Administration, convened by the Secretary, DHHS, contains the following recommendation: "In an era of rapid technological advancement, the FDA must reaffirm its commitment to research as an integral component of its activities. The FDA's intramural and extramural research projects must be linked to the Agency's primary functions." The Section of the Report entitled "Scientific Capabilites and Research,"states that "High levels of scientific expertise are required to review product applications and to respond to public health crises...FDA scientists who are actively engaged in research help build a vital foundation of Agency understanding and expertise. Without that foundation, the Agency's ability to address emerging regulatory problems is hampered...It is essential that the FDA avoid being blind-sided by rapid advances in biomedical science and technology. Maintaining relevant research activities can serve that goal and help more generally in recruiting and retaining needed scientific talent. To be useful, research must strike a balance between targeted and exploratory projects and between intramural and extramural activities. To achieve that balance, the Agency must better manage its research operations.....A thorough peer review process is one tool to ensure the scientific integrity and quality of both intramural and extramural research."
It is remarkable to note throughout this abbreviated historical review the consistent themes of powerful affirmation of the centrality of high quality scientific research to the regulatory missions of the FDA and its predecessor agencies, and the persistent expressions of dissatisfaction with the quality and credibility of those agencies' scientific programs. Recurrent efforts over many decades to respond to this dissatisfaction have led to the creation of numerous committees, commissions and advisory panels, whose astonishingly consistent findings and recommendations have generally resulted in calls for major change in the oranization and management of the agencies' scientific endeavors.
In spite of repeated attempts to effect the desired changes, by establishing, and apparently then disestablishing, new research organizations (Centers, Bureaus, at least one Institute) and repetitively recreating the senior management position of Scientific Director under different appellations, the need for such frequent, periodic repetition of the process indicates that the efforts have consistently failed. The critical question is, why? Although the reasons for failure are not self-evident from this abbreviated history, close reading of documents strongly suggests that the dominant cause was the persistent dilemma posed by well-intentioned scientific aspirations, a burden of ever increasing regulatory mandates and complexities, and annual budgets that were chronically insufficient to meet the desired objectives.
David M. Kipnis, M.D. (Chair)
Distinguished University Professor of Medicine
Department of Internal Medicine
Washington University School of Medicine
Leslie Z. Benet, Ph.D.
Professor and Chairman
Department of Biopharmaceutical Sciences
School of Pharmacy
University of California San Francisco
Ruby P. Hearn, Ph.D.
Senior Vice President
Robert Wood Johnson Foundation
William J. Rutter, Ph.D.
Emeritus Professor of Biochemistry
University of California at San Francisco
and
Chairman
Chiron Corporation
Robert S. Langer, ScD.
Kenneth J. Germeshausen Professor of Chemical and Biomedical Engineering
Massachusetts Institute of Technology
Gilbert A. Leveille, Ph.D.
Vice President, Research and Technical Services
Nabisco, Inc. (retired)
Richard B. Setlow, Ph.D.
Associate Director, Life Sciences
Brookhaven National Laboratory
Flossie Wong-Staal, Ph.D.
Florence Riford Chair in AIDS Research
Professor of Medicine & Biology
University of California at San Diego
Frank L. Douglas, Ph.D., M.D.
Executive Vice President, Global Research
Hoechst Aktiengesellschaft
Hoechst Marion Roussel, Inc.
Pedro Cuatrecasas, M.D.
President, Pharmaceutical Research
Parke-Davis (retired)
Rita Colwell , Ph.D., D.Sc. (Hon.)
President
Maryland Biotechnology Institute
University of Maryland Biotechnology Institute
Charles A. Sanders, M.D.
Chairman
Glaxo, Inc. (retired)
All professional affiliations are
listed for identification purposes only.
March 11, 1997
Hypertext created on 03/14/97 by Jonathan Boswell, OSB, Center for Devices and Radiological Health.