[Federal Register Volume 66, Number 163 (Wednesday, August 22, 2001)]
[Notices]
[Pages 44146-44149]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 01-21145]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES


Notice of Meeting

AGENCY: Office of the Secretary, HHS.

ACTION: Notice of meeting.

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    At the request of the Secretary, a meeting will be held to 
determine if and how the Public Health Service Bovine Spongiform 
Encephalopathy/Transmissible Spongiform Encephalopathy (BSE/TSE) Action 
Plan can be expanded to capitalize on the human and physical resources 
of the pharmaceutical and biotechnology industries. A copy of this plan 
is appended to this Notice. The meeting will be held in the Office of 
the Secretary, Hubert H. Humphrey Building, 200 Independence Ave. SW., 
Washington, DC 20201 on Monday, September 24, 2001, from 9 a.m. to 3 
p.m. Because of space limitations, attendance at the meeting will be 
limited to approximately 100 persons, and will therefore be limited to 
those who have preregistered.
    Up to 30 of the approximately 100 spaces available will be reserved 
for those who submit a written proposal of no more than two single-
spaced pages in length, and preferably no more than one page, that 
describes in general terms (1) needs in areas of basic research on any 
aspect of BSE or any TSE that are currently unmet and (2) human and 
physical resources under their control that could be recruited to 
support this research. This solicitation of ``industries'' is directed 
at industries of all sizes, and to non-profit as well as for-profit 
entities.
    Preference for the 30 reserved spaces will be given to those whose 
proposals are received by the undersigned no later than close of 
business Friday, August 31, 2001. A paper copy and an electronic copy 
in either Microsoft Word (R) or WordPerfect (R) format are requested, 
but fax and e-mail submissions will be accepted. Proposals must include 
a return mailing address, individual to contact, and telephone number 
of that individual. If available, a fax number and an e-mail address 
should also be provided.
    A period of up to one hour will be reserved for public comment. 
Persons who wish to comment on their own proposal or any other matter 
will be asked to do so for no more than 5 minutes.
    The sole purpose of this meeting is to gather information. No 
decisions will be made at this meeting. A transcript and a summary of 
the meeting will be available from the undersigned on or before October 
8, 2001.
    Those considering submission of a proposal or speaking at the 
meeting are advised that all information received in response to this 
Notice will be considered to be in the public domain.

For Registration or Further Information Contact

    Stephen D. Nightingale, M.D., Office of Public Health and Science, 
Department of Health and Human Services, 200 Independence Ave., SW., 
Washington, DC 20201, phone (202) 690-5558, fax (202) 260-9372, e-mail 
StephenDNightingale@osophs.dhhs.gov.

    Dated: August 17, 2001.
Stephen D. Nightingale,
Executive Secretary, Advisory Committee on Blood Safety and 
Availability.

Bovine Spongiform Encephalopathy/Transmissible Spongiform 
Encephalopathy (BSE/TSE) Action Plan

Background

    Bovine spongiform encephalopathy (BSE), or ``mad cow disease,'' was 
first recognized in the United Kingdom in 1986. Major efforts were 
undertaken to control the BSE epidemic that followed. These included 
the precautionary slaughter of about 4.5 million asymptomatic cattle, 
and increasingly broader prohibitions against recycling animal tissues 
and byproducts into the food chain through livestock feed supplements. 
There is compelling epidemiological evidence that these actions 
reversed the course of the BSE epidemic within the United Kingdom.
    Unfortunately, these measures were insufficient, or not instituted 
in time, to prevent the occurrence of BSE in other European countries. 
These initially included France, Ireland, Portugal, and

[[Page 44147]]

Switzerland, and have more recently included Belgium, Denmark, Germany, 
Italy, Netherlands, and Spain. However, BSE has not yet been found in 
the United States.
    BSE is one of several transmissible spongiform encephalopathies 
(TSEs). Other animal TSEs include scrapie in sheep and goats, and 
chronic wasting disease (CWD) of deer and elk. Scrapie and CWD are 
found in the United States. Human TSEs include kuru, a disease of the 
South Pacific Fore people; Creutzfeldt-Jakob disease (CJD), which 
occurs throughout the world, including the United States (where it 
occurs at a stable rate of about 1 per million population per year); 
and new variant CJD (vCJD), which was first reported in the United 
Kingdom in 1996. There is no evidence to date of vCJD in the United 
States. There is no known treatment for any TSE, and they are all 
invariably fatal.
    The TSEs are named for the characteristic spongelike appearance 
associated with deposits of proteins, called prions, that are found in 
patients' brains. In some but not all TSEs, there are characteristic 
deposits of prions, sometimes detectable preclinically, in other 
tissues as well. Prions are proteins that have been highly conserved in 
mammalian evolution, but whose function is not well understood. They do 
not cause disease in their native state, but only when they become 
abnormally folded.
    What causes the abnormal folding to occur, why affected individuals 
cannot dispose of or develop immunity to these proteins, and what 
factors other than the prions themselves affect the transmission or the 
pathogenesis of the TSEs are poorly understood. In particular, the lack 
of a sensitive and specific noninvasive test for either animal or human 
TSEs, or methods for identifying those at increased risk of a TSE, are 
major obstacles to progress. However, recent investigations in this 
field appear to hold substantial promise.

Issue

    The report of vCJD (a disease of humans) in the United Kingdom only 
ten years after the recognition of BSE (a disease of animals) was by 
itself an event of great concern. This concern has been reinforced by 
the findings that the transmissible agent of BSE and the transmissible 
agent of vCJD are indistinguishable by current bioassays from each 
other; that BSE has spread from the United Kingdom to other countries, 
and that vCJD has begun to appear in some countries to which BSE has 
spread. These events call for a vigorous DHHS effort--coordinated with 
those of other government agencies, the private sector, and the 
international community--to contain this epidemic and assist those 
affected by it.

Response

    The BSE/TSE Action Plan of the Department of Health and Human 
Services (DHHS) has four major components: Surveillance, Protection, 
Research, and Oversight. Surveillance for human disease is primarily 
the responsibility of the Centers for Disease Control and Prevention 
(CDC). Protection is primarily the responsibility of the Food and Drug 
Administration (FDA). Surveillance of animals, feeds, and foods is also 
a responsibility of FDA, which it shares with the United States 
Department of Agriculture (USDA). Research is primarily the 
responsibility of the National Institutes of Health (NIH). Oversight is 
primarily the responsibility of the Office of the Secretary (OS). Core 
actions in each area are as follows:
1. Surveillance--CDC
    A foundation of CDC disease surveillance and outbreak investigation 
activities is its relationship with--and support of--state and local 
health agencies and officials, who are often the first to encounter 
newly emerging human diseases or changes in the epidemiology of 
recognized human diseases. These relationships complement those that 
CDC maintains with health care providers and institutions such as 
healthcare facilities. These relationships are designed to maximize the 
likelihood that a sentinel event will be detected as soon as it occurs, 
whether in an expected or an unexpected location.
    CDC collects, reviews, and when indicated actively investigates 
reports by health care personnel or institutions of possible CJD or 
vCJD cases. CDC also monitors overall mortality data and carefully 
scrutinizes mortality data in certain populations (for example, persons 
with hemophilia). In addition, after the report of vCJD in the United 
Kingdom in 1996, CDC augmented its domestic CJD surveillance. Because 
of the striking age differences between vCJD and CJD patients, CDC, in 
partnership with state and local health departments, initiated post-
mortem followup investigations of patients diagnosed with CJD who were 
less than 55 years of age at death. In 1996-1997, CDC established, in 
collaboration with the American Association of Neuropathologists, the 
National Prion Disease Pathology Surveillance Center at Case Western 
Reserve University, which performs special post-mortem tests for vCJD.
    Under this Action Plan, CDC will provide additional financial and 
technical support for state and local health department surveillance 
for CJD and vCJD cases. The Action Plan anticipates the need for more 
case investigations and risk assessments, particularly if the 
epidemiology of vCJD changes. The action plan will increase the range, 
accuracy and timeliness of current efforts.
    The proposals are as follows:
    A. By the end of 2001, CDC will support cooperative agreements with 
state and local health departments to:
    i. Enhance pre-mortem surveillance to increase the number of post-
mortem studies on individuals, who by virtue of their symptoms (e.g., 
ataxia or dementia) and situations (e.g., long exposure to food 
products from the United Kingdom) might be at increased risk for TSEs, 
and
    ii. Expedite national surveillance of CJD through accelerated 
review of CJD mortality data and clinical investigation of all such 
cases under 55 years of age to identify possible cases of vCJD.
    B. CDC will enhance its current collaborative agreement with the 
National Prion Disease Pathology Surveillance Center at Case Western 
Reserve University by the end of FY 2001.
    C. CDC will enhance and expand infection control recommendations to 
protect patients and health care workers from the potential 
transmission of TSE in healthcare facilities by the end of FY 2002.
    D. CDC will maintain and, as appropriate, expand its contact with 
national and local health officials in countries that have found, or 
may find, new or increasing numbers of animal or human TSEs within 
their borders (FDA and NIH, in the course of actions described below, 
will do the same with their regulatory and scientific counterparts).
    The following additional activities and expansion of A above will 
require additional or reallocated resources.
    A. CDC will enhance and expand its technical assistance to the 
increasing number of state and local health personnel whom these 
cooperative agreements will make available to identify and investigate 
possible cases of TSEs.
    B. CDC will develop laboratory capacity at its main campus to 
provide analytic support for health investigations, and to conduct 
research on methods to improve these investigations by the end of FY 
2003. This activity will depend on the

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completion of new laboratory space, anticipated to become available in 
FY 2004.
2. Protection--FDA
    The foundations of FDA consumer protection and health promotion 
activities are rigorous application of scientific knowledge to 
regulatory policies and actions, appropriate caution when scientific 
knowledge is insufficient to determine the optimal policy or action, a 
strong regulatory infrastructure to assure compliance with established 
regulations, and aggressive pursuit of the scientific knowledge 
necessary to anticipate as well as resolve regulatory issues. 
Maintenance of an environment in which these practices can flourish 
requires timely and open dialogue about the agency's actions, and the 
reasons for its actions, with both stakeholders on specific issues and 
with the public at large.
    Consistent with this overall strategy, FDA has undertaken five 
major initiatives to enhance, sustain, and communicate safeguards. 
These are:
    A. FDA, in partnership with USDA, seeks to prevent exposure of the 
public to TSE agent(s) through food products. FDA will continue and as 
necessary expand its import and animal feed surveillance/inspection 
programs and enforcement actions to control the use of mammalian 
protein in ruminant feed, to keep potentially infected products out of 
the United States, and to address further the issue of CWD in domestic 
deer and elk.
    B. FDA will continue and as necessary expand its policies designed 
to prevent potential exposure to TSE agent(s) through blood transfusion 
and tissue transplantation. Reevaluations occur both on a routine, at 
least semi-annual basis in conjunction with meetings of the FDA TSE 
Advisory Committee, and whenever new information becomes available.
    C. FDA will continue and as necessary expand its policies to 
prevent potential exposure of the public to TSE agent(s) through drugs, 
devices, vaccines, other biologics, cosmetics, food, food additives, or 
dietary supplements that use in their manufacture at-risk bovine 
materials. These efforts are routinely incorporated into the pre-
approval review of new entities that are required to undergo such 
review, and by targeted post-marketing review of specific entities that 
may either contain at-risk bovine materials, or entities that may be 
exposed to at-risk bovine materials during their manufacture. Ongoing 
enhancements to guidances and regulations regarding acceptability of 
source materials for these products are an integral component of this 
effort.
    D. FDA will continue and as necessary expand its coordinated 
education and outreach program to inform consumers, patients, 
practitioners, and industry of the risks of TSEs and of their potential 
transmission through the products that FDA regulates.
    E. FDA will continue and as necessary expand its regulatory 
research agenda regarding TSEs. As noted above, the lack of a 
sensitive, specific, and non-invasive test to detect either humans or 
animals with an increased risk of developing or incubating a TSE is a 
major obstacle to progress against TSEs, and to FDA's efforts to meet 
its consumer protection and health promotion mandates. While FDA is 
encouraged by recent progress in this field, FDA nevertheless feels 
obligated to continue both intramural and extramural research to 
support the development and evaluation of tests for premortem detection 
of TSE agents(s) that will have sufficient sensitivity and specificity 
for diagnostic, screening, and quality control purposes. FDA will also 
pursue studies to evaluate the safety and effectiveness of 
sterilization/decontamination/inactivation procedures for BSE/TSE 
agent(s) so that these procedures can become part of Good Manufacturing 
Practices.

3. Research--NIH

    A foundation of NIH research portfolio management is to maintain a 
balance between its support of research focused on health matters of 
immediate concern, and research that aspires to address concerns that 
may arise in the future. The NIH supports both intramural and 
extramural research, some of which is guided by agency directives, and 
some by proposals of individual investigators. In addition to fostering 
individual proposals, the NIH fosters the training and professional 
development of the young investigators necessary to sustain the 
country's research efforts in the future.
    The first scientific work on human TSE to be undertaken anywhere in 
the world was initiated on the NIH campus in the early 1960's. 
Currently NIH funding for TSE research, which is provided for 
investigators throughout the United States, is focused on four areas:
    i. Understanding the prions that cause TSEs;
    ii. Defining how TSEs are transmitted among animal species and, 
most importantly, across apparent species barriers;
    iii. Developing diagnostic tests for animals and humans using 
tissues and blood;
    iv. Designing drug therapy.
    Pursuant to these goals, major TSE research programs are currently 
being supported by the following institutes:
    i. The National Institute of Neurological Disorders and Stroke 
(NINDS) supports basic and applied research on TSEs in both its 
intramural and extramural programs. Prior accomplishments of the 
intramural program have been recognized by the award of the Nobel Prize 
to Dr. Carleton Gadjusek for demonstrating that both kuru and CJD were 
transmissible, and prior accomplishments of the extramural program have 
been recognized by the award of the Nobel Prize to Dr. Stanley Prusiner 
for his work on prions. NINDS funding for TSE research was $8.87 
million in FY 1999 and $12.75 million in FY 2000.
    ii. The National Institute of Allergy and Infectious Diseases 
(NIAID) also supports both intramural and extramural research on TSEs, 
with a particular focus on chronic wasting disease (CWD) of deer and 
elk. The intramural NIAID program, which is conducted at the NIAID 
Rocky Mountain Laboratories in Hamilton, Montana, has developed 
genetically engineered mouse models of scrapie and CWD and used these 
to study the effects of particular genes and of species barriers on the 
natural history of these diseases. The laboratory has also initiated a 
drug discovery program. Renovation of the Rocky Mountain facilities 
devoted to TSE research is currently under way, at a cost of $1.62 
million dollars. In FY 2002, NIAID expects that roughly $1 million will 
be allocated to the Rocky Mountain Laboratories for support of TSE-
related research.
    iii. The National Heart, Lung, and Blood Institute (NHLBI) is the 
lead institute within NIH for the development of tests for TSEs that 
would be suitable for screening the blood supply. The research 
currently funded is targeted at developing and validating test 
strategies for various human and animal TSEs in samples of known 
infectivity. This program includes two contracts jointly sponsored by 
NHLBI and NINDS that run from fall 2000 to fall 2005 and three NHLBI-
initiated research grants that run from fall 2000 to fall 2003. NHLBI 
funding for TSE research was $0.9 million in FY 1999 and $2.2 million 
in FY 2000.
    Efforts in all of the above areas are being expanded. However, 
there is a critical shortage of investigators and specialized 
laboratory facilities that can

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handle the hazardous material used in studies of TSEs. A goal of the 
NIH is to address these needs by mounting a coordinated effort among 
the Institutes at NIH as well as with other Federal agencies to achieve 
these objectives:
    A. Establish a repository for research reagents by the next fiscal 
year;
    B. Double the laboratory facilities available over the next two 
years;
    C. Triple the number of investigators involved in TSE research over 
the next five years;
    D. Double or if possible triple current spending for TSE research 
by the end of FY 2002. To do this, the NIH will convene a special 
meeting to identify the major needs and opportunities for research in 
this field. The product of this workshop will form the basis of a 
Request for Applications. The scientific quality of the applications 
received will determine the total funding committed to this initiative. 
The Acting Director, NIH, has agreed to provide funding as needed for 
this purpose from the Director's Discretionary Fund.
    E. Consider, in consultation with OS, the establishment of a 
``prize'' of about $1 million for the first person(s) or 
organization(s) to provide proof of principle for the development of a 
minimally invasive test that would be sufficiently sensitive and 
specific for screening random populations for presymptomatic infection 
with CJD or vCJD, and a ``prize'' of about $5 million to the first 
person(s) or institution(s) to obtain FDA approval and to place into 
commercial distribution a minimally invasive screening test that would 
be sufficiently sensitive and specific for screening random populations 
for presymptomatic infection with CJD or vCJD.
4. Oversight--OS
    The foundations of OS oversight activities are the statutory 
obligations of the Secretary, and the lessons that have been learned 
from experience with the HIV and hepatitis C epidemics.
    In 1995, at the request of the Department, the Institute of 
Medicine (IOM) issued a report titled ``HIV and the Blood Supply: An 
Analysis of Crisis Decisionmaking.'' The IOM recommended that the 
Secretary establish a Public Health Service (PHS) Blood Safety 
Committee (BSC). The Secretary designated the Assistant Secretary for 
Health to be the chair of this committee and to be the Blood Safety 
Director for the Department. Other BSC members are the directors of 
CDC, FDA, and NIH; the Assistant Secretary for Planning and Evaluation; 
and the Associate General Counsel for Public Health. This committee 
exists so that threats to the safety or availability of the blood 
supply can be brought immediately to the highest levels of the 
Department. The BSC has met on the issue of deferring blood donors at 
risk of transmitting BSE by virtue of prior residence in the United 
Kingdom. The BSC also met on issues relating to the development of CJD 
at an unusually young age in a hunter who had been a long time plasma 
donor, and on issues related to the discovery of a poorly characterized 
TSE that recently appeared in two flocks of East Freisian sheep which 
had been imported to Vermont from Belgium. The group stands ready to be 
convened for similar matters in the future.
    The Department has also established an Interdepartmental Steering 
Committee for BSE/TSE Affairs. This committee is chaired by the 
Commissioner of FDA and includes representatives of CDC, FDA, NIH, 
USDA, the United States Trade Representative, the Office of Management 
and Budget, the Customs Service, the Department of State, the 
Department of Defense, the State Association of Feed Control Officials, 
the National Association of State Departments of Agriculture, and the 
White House Office of Science and Technology Policy. This committee 
assures ongoing coordination between agencies; integrated contingency 
planning in case BSE or of vCJD is found in the United States; 
identification of and response to potential vulnerabilities in the 
United States to BSE and vCJD; and coordination of risk communication 
plans by the various agencies. A summary of each meeting of this group 
will be forwarded through the Assistant Secretary of Health to the 
Secretary within thirty days of each meeting, and on a more expedited 
basis as necessary.
    The Department must assure timely, accurate, thorough, and clear 
communication to the public about the nature and extent of the threats 
posed by BSE/TSE and about the actions that each agency of government 
is taking to protect the public from these threats. In addition, each 
agency must anticipate the worst case scenarios of a case of BSE or of 
vCJD being recognized in the United States, and each agency must have a 
plan not only for dealing with this contingency but also for 
communicating the event itself, and the agency response to the event, 
to the public. Furthermore, the communications of the various agencies 
must be consistent with each other. For this reason, the BSE/TSE 
Steering Committee will establish a communications workgroup to develop 
an interdepartmental communications strategy and plan for dealing with 
a potential occurrence of BSE and/or vCJD and serve as a public 
affairs/communications resource in dealing with BSE/TSE issues.
    Also, the FDA TSE Advisory Committee meets publicly on at least a 
semi-annual basis. One standing agenda item of this committee is review 
of current regulations and guidance to prevent exposure of the United 
States population to the agent(s) of BSE/TSE through blood, tissues, 
and other regulated products. A summary of this meeting, with 
particular attention to this agenda item and to public comment about 
it, will be forwarded through the Assistant Secretary for Health to the 
Secretary within thirty days of each meeting, and on a more expedited 
basis as necessary.
    Issues that warrant OS oversight at this time include the 
following:
    A. Assurance of adequate program support to enhance TSE 
surveillance by CDC as planned.
    B. Assurance of adequate program support for FDA regulatory and 
research activities related to TSEs.
    C. Assurance of adequate program support for the TSE research 
initiatives proposed by NIH.
    D. Assurance and coordination of integrated risk communication 
messages to the public and to industry regarding the true nature of 
threats posed by BSE/TSEs, particularly in the event of a confirmed 
case within the United States.
    E. Assurance of a seamless collaboration with USDA and other 
federal and state agencies on BSE/TSE issues.

[FR Doc. 01-21145 Filed 8-21-01; 8:45 am]
BILLING CODE 4150-28-P