May 7, 2003
Mr. Chairman and Members of the Subcommittee, I am Dr. Murray Lumpkin, Principal Associate Commissioner at the Food and Drug Administration (FDA or the Agency). I appreciate the opportunity to appear today to discuss FDA's role in the national and international response to the emerging threat of severe acute respiratory syndrome (SARS).
FDA is presently helping in five specific areas in the battle against SARS by working with other government agencies, industry and academia to:
Our goal is to continue to work closely with public and private entities to protect the U.S. population from the public health risk associated with SARS and to facilitate the development of products in which American practitioners and patients can have confidence to help those afflicted with this disease.
Department of Health and Human Services Coordination
The Department of Health and Human Services (DHHS or the Department) is providing overall national direction, guidance and coordination in the fight against SARS. Under this umbrella, FDA is working closely with other agencies, such as Centers for Disease Control and Prevention (CDC) and National Institutes of Health (NIH), as well as with the private sector, State health officials, and other relevant agencies, to expedite the development of reliable diagnostic, preventive, and treatment tools for SARS and to provide emergency access to promising products as needed.
The epidemic of SARS has been very fast moving. Because of the novelty of this pathogen and the lack of previous experience with this specific disease, as with other public health agencies, FDA is presently in the initial stages of its response to the disease. Yet the Agency has already taken a number of steps to address a possible escalation of SARS cases in the United States. Let me elaborate on specific measures with which the Agency is involved.
Development and Approval of Diagnostics
Currently, there are no marketing applications for a SARS diagnostic product before the Agency. This is not surprising given that we are still in the preliminary stages of our understanding of SARS. However, FDA is working closely and proactively with other government agencies such as CDC and NIH, as well as with the private sector, to foster the development of reliable diagnostic tools that will help identify the microbiological agent of SARS from patient specimens and will help confirm whether or not a patient is or has been infected with this SARS agent.
The mission of FDA's Center for Devices and Radiological Health (CDRH) includes guaranteeing the safety and reliability of diagnostic tools, such as those under development that will allow the identification of the SARS agent. CDRH is working with CDC, who along with others in the SARS Laboratory Network organized by World Health Organization (WHO), is helping further the scientific understanding of the virus. A diagnostic test for SARS, based on the detection of RNA sequences in the novel coronavirus, is currently under development along with an ELISA (enzyme-linked immunosorbent assay) test for antibodies to the SARS-related virus. The first of these tests, using polymerase chain reaction (PCR) technology, will help with acute diagnoses of patients, while the ELISA test will be used to confirm a case during or after convalescence. CDC developed these prototype experimental reagents over the past two months in an effort to address this unmet public health need. FDA rapidly reviewed information for the investigational use of this test, and is working closely with CDC to develop appropriate information for patients and health professionals, and an approach for further evaluation of this new test. Working with our CDC colleagues, FDA guided CDC in drafting an investigational device exemption (IDE) for the PCR technology assay. This IDE has been provisionally approved. This test methodology will be distributed to approximately 100 specialized laboratories around the country. Under the terms of this test's wider distribution, patients and practitioners will receive clear information about the test when it is used to assist in diagnosing SARS. Hopefully, this information will facilitate the development and evaluation of an approved diagnostic test as quickly as possible.
As SARS is a serious and life-threatening disease for which there are no presently approved diagnostic tests, the disease meets our standard for priority review to expedite the development of new tests and the review of these tests marketing applications. CDRH is already reaching out to industry to ensure that any development plans for new tests are well designed and that premarketing applications submitted to the Agency are of such quality that a priority review can swiftly proceed. In addition, FDA has already cleared or approved dozens of tests for use in differential diagnosis of acute respiratory syndromes and has put in place a postmarket surveillance program to measure how well these tests are working. These tests do NOT diagnose SARS; rather they help to diagnose other conditions that may have symptoms similar to SARS. In this way SARS can be ruled out as the diagnosis in these patients.
Development and Approval of Therapeutics
Although to date there have been no marketing applications for therapeutic products for the treatment of SARS submitted to FDA, the Agency is indeed working to help facilitate the development of safe and effective treatments for patients suffering from SARS. The Center for Drug Evaluation and Research (CDER) and the Center for Biologics Evaluation and Research (CBER) are both responding to this need by identifying drugs and other therapeutics products that may be effective in combating the SARS agent or modifying the course of the disease. CDER is working expeditiously with CDC and NIH to design and implement both emergency protocols and protocols for properly controlled clinical trials for using these anti-viral products to treat SARS patients who meet certain medical criteria for inclusion in the protocols. Because of this close collaboration, the U.S. is now better prepared to respond quickly to any escalation of SARS cases and to evaluate the potential effectiveness of treatments and thus help patients and practitioners around the world further their understanding of the best ways to treat this disease.
With regard to specific therapeutics, CDER is engaged with those who are trying to identify compounds for additional screening and is interacting with pharmaceutical companies on these compounds. CDER has identified 16 compounds, mostly nucleoside analogues, from ten companies for in vitro screening against the coronavirus and has provided those companies contact information from the NIH and U.S. Army Medical Research Institute for Infectious Diseases (USAMRIID) screening program. CDER is also working with NIH and USAMRIID to prioritize candidate products for initial in vitro susceptibility testing with the USAMRIID assay.
Much has been written in the press about a drug called ribavirin. The oral and inhalation dosage forms of this product are already approved in the U.S. for treating certain viral infections. The intravenous formulation of ribavirin is still an experimental drug only available in the U.S. under an Investigational New Drug (IND) Application. Various places outside the U.S. have used the intravenous and oral formulations of the product to try to treat those most severely affected by SARS. CDER worked with CDC on the development of an emergency use protocol, which has now been allowed to proceed, that would allow suspected SARS patients who meet certain medical criteria to be treated with intravenous ribavirin should the need arise. To date, no one in the U.S. has been treated with intravenous ribavirin under this protocol. In addition, CDER has assessed the adequacy of ribavirin supplies if it shows therapeutic promise and there is increased demand for the drug in the event that SARS spreads to many more patients.
Unfortunately, in the USAMRIID susceptibility assay, ribavirin did not appear to inhibit the growth of the SARS agent. The relevance of this laboratory finding to the clinical situation remains to be determined; however, what role, if any, ribavirin will play in future therapeutic regimens for SARS in still quite unclear.
No matter what the product being used, it is important to note that caution must be exercised and patients and family members must be fully informed when participating in trials that study investigational drugs to treat SARS. As there is usually little available information about these investigational agents, and the safety and efficacy profiles in SARS have not yet been defined, use must be predicated on adequate informed consent.
Again, SARS is a disease whose novelty and nature make it a prime candidate for therapeutic development under FDA's previously established programs to expedite the drug development and review process through our "fast track" program. The "fast track" program is designed to quickly facilitate the development and review of new drugs intended to treat serious or life-threatening conditions and that demonstrate the potential to address unmet medical needs ("fast track products"). This program emphasizes the critical nature of close, early communication between the Agency and a sponsor, outlines procedures such as pre-IND and end-of-phase-I meetings as methods to improve the efficiency of preclinical and clinical development, and focuses on efforts by the Agency and drug sponsor to reach early agreement on the design of the major clinical efficacy studies that will be needed to support approval. Most importantly, under this program, as various elements of a marketing application are completed these pieces of the application can be submitted for review as soon as they are finished, rather than having to wait for the entire application to be completed, analyzed, assembled, and submitted. In these cases, FDA can begin review of the marketing application much earlier. FDA has made clear that it considers SARS candidate therapies eligible for "fast track" designation.
Development and Approval of Vaccines
FDA is part of the team striving to develop a safe and effective SARS vaccine. On April 9, 2003, Dr. Jesse Goodman, Director of CBER, joined Secretary Thompson and key leaders from NIH, CDC, and the National Vaccine Program Office to answer questions from vaccine manufacturers concerning approaches to developing a SARS vaccine. CBER is strongly committed to working proactively with industry and government partners to facilitate such development under the same type programs for these kinds of public health needs as those utilized by CDRH and CDER. The Center is pursuing multiple potential vaccine development strategies. CBER is working with other government agencies and the private sector to address many of the most difficult issues in early vaccine development. In this process, CBER provides guidance on the use of animal test data and on safe manufacturing practices. The Center will also be a major participant in the design of clinical trials and in defining the needs of special populations (such as pregnant women). As the SARS vaccine program is in its infancy, much painstaking work will be necessary to assure that the development and manufacturing processes meet the standards required to develop and produce safe and effective vaccines from which people have benefitted so much over the years. While we hope that a safe and effective SARS vaccine can be developed, and we will do everything feasible to help facilitate and speed the development process, at this early stage of scientific knowledge about the nature and stability of the virus and the human immunological response to the virus, it would be imprudent and unfair to over-promise about any possible timeline for a SARS vaccine.
As with therapeutic products, FDA can and will expedite the vaccine review process to address critical needs. Given the potential public health impact of SARS infection, FDA places a high priority on facilitating the development and review of such products. We work to maintain open and continued dialogue with vaccine manufacturers and to assist firms that seek to enter the vaccine manufacturing market. FDA routinely meets with manufacturers during all stages of the development of vaccines and prior to submission of a licensing application to facilitate the regulatory process and provide guidance on requirements for new vaccines. The Agency also encourages and works with manufacturers to enhance their production capabilities and capacities.
FDA's Center for Veterinary Medicine (CVM) has investigated products used in the treatment of animal coronaviruses, and that information has been relayed to CBER and the wider community so that any potential relevance to SARS can be investigated. For example, effective and safe vaccines are marketed for enteric diseases caused by coronaviruses in cattle, swine, dogs, and cats; effective and safe vaccines, both live and killed, are marketed for avian infectious bronchitis caused by a coronavirus; and diagnostic test kits are marketed for feline infectious peritonitis, and for avian infectious bronchitis due to coronaviruses.
Assuring An Adequate Supply of Related Medical Products
FDA is working with manufacturers to assure adequate supplies of various medical products that would be needed in the event of a broader spread of SARS in the U.S. For example, CBER, CDER, and CDRH are developing master lists and evaluating the adequacy and supplies of respirators, emergency medical supplies (gowns, gloves, masks), complex medical devices (ventilators, cardiac monitors), and the routine therapeutic products required to adequately support critically ill patients.
Protecting the Nation's Blood Supply
While there is no evidence that the SARS agent can be spread by blood, in mid-April, FDA nonetheless issued guidance to the nation's blood establishments on measures to further safeguard the blood supply against the threat of SARS while further scientific knowledge about the potential spread of this agent is obtained. This decision was based on the preliminary scientific data indicating that SARS is caused by a unique coronavirus that may be present in the blood of some infected persons early in their illness. Although the SARS epidemic has been limited in the U.S. and transfusion transmission of SARS has not been documented to date, it seemed prudent to act as quickly as possible to implement measures to restrict its spread, and in particular to protect the blood supply so that, if it is ultimately shown that the agent can be spread by blood, we will have taken steps to protect the nation's blood supply. The new SARS guidance sets forth measures for temporarily deferring potential donors who may have been exposed recently to SARS or recently had SARS. These measures include limited additional questioning of potential donors to help ascertain if they may be at elevated risk for SARS due to recent travel to known high risk areas as defined by CDC or due to exposure to a person with SARS or suspected SARS. FDA regularly exchanges information with CDC, NIH, the Department of Defense, and blood collection and distribution organizations to monitor SARS epidemiology and pathogenesis, in particular, as it relates to blood safety. FDA will continue to monitor this evolving situation and revise or supplement the guidance as needed to preserve the safety and availability of the blood supply, based on the best available information.
It is important to re-emphasize that transfusion transmission of SARS has not been reported. However, CDC and others are conducting studies to clarify if the implicated coronavirus is present in the bloodstream during the asymptomatic incubation period of early infection. The public health need for testing donors, therefore, has yet to be established but FDA believes, given the state of scientific knowledge at this time, that this is the most prudent way to proceed. In addition, FDA is also in dialogue with SARS test kit manufacturers to help lay the groundwork for development of blood screening assays, should it be necessary.
SARS as a Model for Bioterrorism Response
The President's Initiative on Countering Bioterrorism is comprised of a number of essential elements in which FDA plays an integral role. 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 FDA scientists is crucial to the success of the expedited development and review process. Our scientists must have expertise in these areas in order to expedite the licensing and approval process for these products. The resources that FDA has received to support bioterrorism preparedness and the expertise we have gained in rapid response and proactive approaches to product development have been helpful as we respond to SARS.
Preparedness for and response to an attack involving biological agents are complicated by the large number of potential agents (most of which are rarely encountered naturally), their sometimes long incubation periods and consequent delayed onset of disease, and their potential for secondary transmission. In addition to naturally occurring pathogens, agents used by bioterrorists may be genetically engineered to resist current therapies and evade vaccine-induced immunity.
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 unknown infectious agent that has proven rapid worldwide diffusion and secondary transmission. The SARS experience reinforces 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. It has highlighted the need for on-going coordination and communications among international public health organization, counterpart public health organizations in other countries, Federal, State and local governments in our country, the public health and medical infrastructures thought the U.S., and with private industry.
Clearly, much remains unknown about SARS at this time. FDA is carefully tracking and participating as a full partner where we have expertise to offer in the scientific undertakings to further define, treat, and, ultimately, defeat SARS. In meeting its public health mandate in this situation, we are ensuring that FDA resources are aggressively, safely, and intelligently deployed in the battle against this new virus. We will continue to work closely and share information with our partners in CDC and NIH, as well as with the private sector and other relevant agencies, to speed the development of reliable diagnostic, preventive, and treatment tools for SARS.
Thank you very much for the opportunity to testify today. I welcome your ideas and your questions.
Last Revised: May 7, 2003