Statement of Lester M. Crawford, July 17, 2003

! Facilitate the development of reliable diagnostic tools;

! Facilitate the development of safe and effective treatments for patients suffering from infectious disease;

! Facilitate the development of a safe and effective human vaccine to prevent the disease; and

! Help safeguard regulated products against the possible transmission of an infectious agent to a consumer of the regulated product e.g. blood and food products.

In describing FDA’s role in responding to this type of threat, let me first elaborate on these specific Agency measures to facilitate the development of products for diagnosis, treatment, and prevention of an emerging zoonotic disease, as well as additional measures to help ensure the safety of regulated products against the possible transmission of an infectious agent. Then, I will briefly describe some of FDA’s activities in responding to the recent monkeypox outbreak.

FDA’s Role in Facilitating the Development of Effective Products to Diagnose, Treat, or Prevent an Emerging Infectious Disease and in Protecting Consumers from Potentially Infective Regulated Products

Depending on a particular disease threat from an exotic animal species, FDA’s response could be expected to involve, but not necessarily be limited to, several key activities:

Facilitate the development of reliable diagnostic tools.

The mission of FDA’s Center for Devices and Radiological Health (CDRH) includes working to ensure the safety and reliability of diagnostic tools that will allow the identification of infectious agents that are a threat to public health. An emerging infectious disease may have no or minor symptoms, such as in the case of West Nile Virus, or have more easily clinically identifiable symptoms, such as smallpox or monkeypox. It is critical in being able to manage each disease and the range of diseases to have accurate and sensitive diagnostic tools. FDA routinely works closely and proactively with other government agencies such as Centers for Disease Control (CDC) and National Institutes of Health (NIH), as well as with the private sector, to foster the development of reliable diagnostic tools for emerging infectious diseases.

I am pleased to tell you that on July 9, 2003, FDA cleared the first test or use as an aid in the clinical laboratory diagnosis of West Nile infection. The new test for West Nile virus infection works by detecting the levels of a particular type of antibody, IgM, to the disease in a patient’s serum. IgM antibodies can be detected within the first few days of the onset of illness and can assist in diagnosis. FDA was committed to the rapid review of this test, and its approval provides a useful tool just in time for the start of the West Nile season.

Facilitate the development of safe and effective treatments for the infection.

FDA works to facilitate the development of safe and effective treatments for patients suffering from emerging infectious diseases. FDA’s Center for Drug Evaluation and Research (CDER) and Center for Biologics Evaluation and Research (CBER) both respond to this need by identifying drugs and other therapeutic products that may be effective in combating an infectious agent or modifying the course of the disease. FDA’s Centers may work cooperatively with CDC and NIH to design and implement both emergency protocols and protocols for properly controlled clinical trials for using products to treat patients who meet certain medical criteria for inclusion in the clinical trials. This collaboration allows the U.S. to be better prepared to quickly respond to an escalation in the number of disease cases and to help patients and practitioners around the world further their understanding of the best ways to treat an infectious disease.

Facilitate development of safe and effective vaccines.

FDA’s CBER regulates vaccine products for humans and USDA’s Veterinary Services (VS) for animals. Vaccines, as with most products regulated by FDA, undergo a rigorous review of laboratory and clinical data to ensure the safety, efficacy, purity and potency of these products. Vaccines approved for marketing may also be required to undergo additional studies to further evaluate the vaccine and often to address specific questions about the vaccine's safety, effectiveness, or possible side effects.

Vaccines are an important tool in preventing and treating emerging infectious diseases. In some cases, vaccine development may potentially be the most viable strategy to address a specific public health threat. FDA facilitates the development of vaccines by conducting intramural research, as well as working cooperatively with CDC, NIH, and the private sector.

In the case of monkeypox, experience in Africa showed a reduced risk of monkeypox for individuals who had previously been vaccinated against smallpox. CDC recommends and is offering smallpox vaccination under Investigational New Drug (IND) to people who have been exposed to monkeypox or who are likely to become exposed. Persons can be vaccinated up to 14 days after exposure.

Helping safeguard the blood supply.

The FDA is responsible for ensuring the safety of our blood supply. The Center for Biologics Evaluation and Research (CBER) regulates the collection of blood and blood components. The FDA has taken tremendous steps in recent years to greatly enhance the safety of our blood supply. While we continue to face new challenges, the American public can be assured that FDA is vigilant in its efforts to keep blood as safe as possible.

One of the challenges of safeguarding and promoting the blood supply is responding to infectious disease outbreaks. It is a challenge that FDA is well prepared to face. FDA works closely with other parts of PHS to identify and respond to potential threats to blood safety, to develop safety and technical standards, to monitor blood supplies and to help industry promote an adequate supply of blood and blood products.

Over a period of years, FDA has progressively strengthened overlapping safeguards that protect patients from unsuitable blood and blood products. FDA's blood-safety system includes the following five measures, all of which are relevant as we address the threat of emerging infectious diseases from exotic animal species:

! Donor screening: Donors are provided educational materials and asked specific questions by trained personnel about their health and medical history. Potential donors whose blood may pose a health hazard are asked to exclude themselves. Donors also undergo medical screening to ensure that they are in good health at the time of donation.

! Blood testing: After donation, each unit of donated blood undergoes a series of tests for blood-borne agents such as HIV-1, HIV-2, HBV (hepatitis B virus), HCV (hepatitis C virus), HTLV-1 and HTLV-II (Human T-Cell Lymphotropic Viruses), and the agent of syphilis.

! Donor lists: Blood establishments must keep current a list of individuals who have been deferred as blood or plasma donors and check all potential donors against that list to prevent use of units from deferred donors.

! Quarantine: Donated blood must be quarantined until it is thoroughly tested and the donation records have been verified.

! Problems and deficiencies: Blood establishments must investigate any failures of these safeguards, and correct system deficiencies that are found by the firms or through FDA inspection. Firms must report to FDA any manufacturing problems, e.g., biological product deviations that may affect the safety, purity, or potency of products that were distributed.

Providing industry and consumers information regarding emerging infectious diseases and blood safety issues is another critically important function. For example, on June 13, 2003, FDA published a notice providing information regarding the monkeypox virus and blood and plasma donors. Individuals with monkeypox usually have clear clinical symptoms and will be deferred from blood donation. FDA also recommends blood and plasma donor deferrals for people who have recently received the smallpox vaccine, which may include individuals exposed to monkeypox.

Ensure the safety of the food supply, including both animals imported for slaughter and imported food products.

FDA has lead responsibility within HHS for ensuring the safety of food products and has the authority to remove a food from the market (or sanction those marketing the food) if the food poses a risk to public health. Exotic animal species may be imported to be slaughtered for food or slaughtered exotic animals or parts of animals may be offered for importation into the U.S.

Globalization of the food supply regulated by FDA presents significant challenges to the Agency. FDA, the U.S. Fish and Wildlife Service (FWS), and USDA’s Food Safety and Inspection Service (FSIS) and the Animal and Plant Health Inspection Service (APHIS) work in close cooperation with the Department of Homeland Security’s Bureau of Customs and Border Protection (BCBP) on items related to imports. FDA issues Import Alerts and Import Bulletins regarding problems or potential problems with imported products under FDA's jurisdiction. FDA coordinates its Import Alerts and Bulletins closely with BCBP and other appropriate Federal agencies. FDA has also established procedures to enhance interagency coordination and to efficiently use Customs' civil monetary penalties procedures against importers who attempt to enter food into the U.S. by means of a material false statement, act, or omission.

To further enhance safety of imported food products, FDA has led a series of food safety workshops around the world in Central America, South America, the Southern Pacific region, Asia, and Africa. These workshops educate foreign governments and food producers on the food safety standards needed to meet U.S. requirements.

Emerging Infectious Diseases and Bioterrorism

The President's plan to combat bioterrorism is comprised of a number of essential elements in which FDA plays an integral role, many of which are the same essential elements that are involved in responding to an emerging infectious disease outbreak. One such element is the expeditious development and licensing of products to diagnose, treat or prevent outbreaks from exposure to pathogens that have been identified as bioterrorist agents. These products must be reviewed and approved prior to the large-scale distribution necessary to create and maintain a stockpile. FDA scientists must guide the products through the development and marketing application review processes, which includes review of the manufacturing process, pre-clinical testing, clinical trials, and the licensing and approval process. This process is extremely complex and early involvement of expert FDA scientists is crucial to the success of the expedited development and review process. FDA’s involvement in bioterrorism preparedness and the expertise we have gained in rapid response and proactive approaches to product development have been and will in the future be helpful as we respond to emerging infectious diseases.

Conversely, how we respond to emerging infectious diseases can serve as a model for preparedness and response to a bioterrorism event in that we are dealing with a previously unfamiliar infectious agent that has proven rapid worldwide diffusion and secondary transmission.

Responding to Monkeypox Outbreak

Monkeypox, a rare, zoonotic, viral disease that occurs primarily in the rain forest countries in central and west Africa, is the most recent emerging infectious disease threat to public health in the United States. Unlike the West Nile Virus, for which we will probably never know the original source of its introduction in the U.S., the epidemiological and animal tracing investigations have determined that all 35 lab-confirmed cases of monkeypox were associated with prairie dogs that appear to have been infected though contact with Gambian giant rats and dormice that originated in Ghana.

As one of my colleagues from CDC is testifying here today on the disease aspects of monkeypox and the epidemiological investigation, I will focus the remainder of my testimony on specific DHHS and FDA actions to control and prevent the spread of the disease.

The Department of Health and Human Service’s Coordination

Section 361 of the Public Health Service (PHS) Act (42 USC 264), gives the Secretary of Health and Human Services the authority to make and enforce regulations to prevent the introduction into and the spread of communicable disease within the United States. Under this authority, the Secretary promulgated regulations (42 CFR 70.2 and 21 CFR 1240.30) giving the Director of CDC and the Commissioner of Food and Drugs the authority to take actions they believe are reasonably necessary to present the spread of communicable diseases. HHS determined that the current monkeypox outbreak, which is not confined by state borders and which, as shown by the presence of the monkeypox virus in prairie dogs, may affect multiple animal species, is a problem that requires the use of this Federal authority. It was imperative that the Department act quickly to establish restrictions on the transport, offer to transport, sale, offer to sell, distribution, offer for commercial or public distribution, release, and importation of various rodent species to prevent the monkeypox virus from spreading and becoming established in the United States.

On June 11, 2003, the Director of CDC and the Commissioner of Food and Drugs, pursuant to 42 CFR 70.2 and 21 CFR 1240.30, respectively, issued a joint order prohibiting, until further notice, the transportation or offering for transportation in interstate commerce, or the sale, offering for sale, or offering for any other type of commercial or public distribution, including release into the environment, of: prairie dogs, tree squirrels, rope squirrels, dormice, Gambian giant pouched rats, brush-tailed porcupines, and striped mice.

The June 11, 2003, order did not apply to the transport of listed animals to veterinarians or animal control officials or other entities pursuant to guidance or instructions issued by federal, State, or local government authorities. In addition, pursuant to 42 CFR 71.32(b), CDC implemented an immediate embargo on the importation of all rodents from Africa (order Rodentia).

FDA has previously invoked Section 361 of the PHS Act to prevent the transmission of communicable disease through shellfish, turtles, certain birds, and human tissue intended for transplantation [see 21 CFR 1240.60 (molluscan shellfish), 1240.62 (turtles), 1240.65 (psittacine birds), and 1270.1 through 1270.43 (human tissue)]. CDC likewise has invoked section 361 of the PHS Act for various purposes.

FDA Actions to Implement the CDC/FDA Joint Order

FDA has taken several steps to quickly implement the Joint Order, closely coordinating activities, as appropriate, with CDC, APHIS, USFWS, CBP, and state and local government counterparts. FDA participated in an Inter-agency conference call held on June 11, 2003, to discuss roles and responsibilities regarding the CDC/FDA Joint Order. In addition, FDA hosted an inter-agency meeting on June 24 with CDC, APHIS, USFWS, and CBP to discuss legal authorities, resources and programs, and cooperation strategies relating to the control of monkeypox relating to the following areas: imports; intra/inter state movements; inspection of dealers, breeders, pet stores, and zoos; quarantine authority; euthanasia and disposition; surveillance of wild animals; exports; and re-exports.

To implement the ban on the domestic transportation of affected animals, FDA:

! Sent the Joint Order to all State Agriculture and Health Agencies, including State and Public Health Veterinarians and State Fish and Wildlife officials, as well as to the Department of Transportation for distribution to rail, airline, and trucking establishments.

! On June 13, 2003, initiated a series of regular conference calls with all 50 states and other Federal agencies to discuss the outbreak and the status of implementation and enforcement of the Joint Order.

! Obtained from APHIS a list of dealers licensed to sell exotic animals and issued a priority assignment to FDA District Offices to work with State counterparts (Departments of Health and State agricultural veterinarians), APHIS, and USFWS to contact and inspect the exotic animal dealers. When dealers are contacted, they are provided with the CDC/FDA Joint Order, the related Federal Register Notice, guidance documents for safe handling of the animals, as well as copies of 21 CFR 1240.30. Dealers with sick animals are identified and referred to the State authorities and CDC to determine what further actions need to be taken.

! Issued on June 27, 2003, (revised July 11) a “Dear Government Authority Letter” (to other Federal, state, and local government authorities) that describes the restrictions on wild-to-wild translocation/transportation of prairie dogs. All interstate translocation/transportation requests, as well as requests for movement within implicated states, are to be referred to FDA for consideration by FDA and CDC.

Conclusion

Our recent experiences with emerging infectious diseases, such as Severe Acute Respiratory Syndrome (SARs), West Nile virus, and monkeypox virus, have reinforced the need for strong public health systems, robust health service infrastructures, and expertise that can be mobilized quickly across national boundaries to mirror disease movements. These experiences have highlighted the need for on-going coordination and communications among international public health organizations, counterpart public health organizations in other countries, U.S. Federal, State and local governments, the public health and medical infrastructures throughout the U.S., and with private industry.

The growing experience and expertise of government agencies at all levels in responding to emerging infectious diseases has been particularly clear in the case of monkeypox. Many program officials in federal, state, and local government agencies worked exhaustively to bring authorities to bear to fight the outbreak and prevent further spread of the monkeypox virus. The level of communication and coordination has been extremely demanding. People at all levels of government have acted decisively, quickly, and in coordination. The forcefulness, persuasiveness, and competence of government actions helped to ensure a high degree of cooperation from the public.

In closing, let me assure you that FDA, and I am sure every Federal, state, and local agency, realizes the need to be vigilant and to continue to evolve and improve our public health infrastructure and other capabilities to be able to respond to the possible nature of future infectious disease threats to public health. FDA looks forward to continuing to work cooperatively with your Committee and others in Congress in preparing for the public health challenges that lie ahead.

At this time I would be happy to answer any questions.