Global Microbial Threats in the 1990s

IV. How can we ensure the availability of drugs, vaccines, and diagnostic tests when they are needed to combat infectious disease emergencies?

U.S. Government role in response to epidemics overseas

Nevertheless, the international public health community relies heavily on U.S. expertise and on U.S.-supported institutions overseas. CDC, NIH, DoD, and USAID may provide technical assistance to WHO when a disease outbreak occurs, and USAID often provides communications facilities as well as financial and logistical support. However, CDC, DoD, and USAID (as well as other U.S. agencies) all face legal, financial, or jurisdictional obstacles when they strive to respond to international infectious disease emergencies. Our ability to respond ensures that we learn of outbreaks quickly. Thus, it is critical to retain that capability.

Supply, production, and distribution of emergency medical supplies

Medical supplies that are frequently required during an epidemic include the following.

Diagnostics
If a country suspects an outbreak of a re-emerging disease (such as Venezuelan equine encephalitis in Peru, plague in India, or cholera in Brazil), health practitioners may lack the diagnostic reagents to confirm the nature of the threat. Without timely confirmation, it is not possible to institute effective control measures or to rule out known diagnoses if a new, or re-emerging disease is suspected. In many cases, diagnostic reagents are available as research tools, but not as standardized commercial products. In such cases, training may be needed to use these research tools appropriately.

Vaccines
If a disease is reliably diagnosed as one that is preventable by vaccine (e.g., diphtheria and yellow fever), vaccinating people in the surrounding area represents the most cost-effective way to protect those people and prevent the disease from spreading. Indeed, smallpox has been eradicated worldwide using a vaccine, saving millions of dollars (see "Savings Due to Vaccination,"). By the year 2000, polio is targeted for eradication as well. Logistical considerations may prevent delivery of doses of a vaccine in time to stop transmission promptly. Where a vaccine is appropriate, a coordinated response network can help gain rapid access to an adequate supply of quality products that meet local requirements. However, if supply needs are greater than can be met by redistribution, the time required for additional production can be lengthy. In such cases, a coordinating infrastructure may be able to mobilize the industrial surge capacity required to meet increased production needs.

Immunoglobulins and Antisera
Individuals who recover from certain infections produce protective antibodies that are present in the bloodstream. When commercially prepared serum from the plasma of former patients is transferred by injection to another person, these antibodies (or immunoglobulins) can provide temporary protection from that disease when a vaccine is not available. Antisera can be made by immunizing animals, such as horses, and the resulting high-titered animal antisera can be used for treatment. Immunoglobulins and antisera can be very important in some situations, but are of limited use for long-term control. In addition, available supplies are generally limited.

Drugs
Many infectious diseases are caused by microorganisms that are susceptible to antibiotic drugs. However, there are occasional regional shortages of antibiotics and in some cases, there may be only a single manufacturer of the material from which the finished product is made. These shortages may worsen as more microbes become drug-resistant and fewer antibiotics remain effective. Antiviral drugs may be of value in some situations, and appropriate studies may be needed to determine their effectiveness.

When an epidemic occurs, diagnostics, drugs, vaccines, and/or antisera are often needed in considerable quantities. However, in many cases they may not be available in sufficient quantities or at the necessary site, and there may be no company or agency with the surge capacity to produce more of them. The supply of medical products is driven by multiple factors, including international market forces; the needs anticipated by U.S. agencies, foreign governments, and international organizations; and the needs stimulated by Government incentives, such as the Orphan Drug Act and national vaccine plans. Some supplies may be available from other countries. However, most countries have national quality control requirements that need to be met. Harmonization of standards internationally along with strengthened local enforcement may enhance the acceptance of emergency medical supplies.

When a drug or vaccine shortage is extensive, the best solution may be to initiate production of additional supplies. However, emergency production is often hampered by insufficient manufacturing facilities, the complexity of production methods, the length of time needed for production and quality control testing, licensure requirements, concerns over liability issues, distribution problems, and/or lack of funds. These difficulties can cause significant delays, giving diseases time to spread. Early detection and rapid coordination should shorten the response time.

Moreover, if the disease is newly emergent, and no treatments or vaccines are available, it is necessary to mobilize the research and public health communities to begin seeking new solutions.

In times of need, interagency Government groups and ad hoc committees try to find remedies as best they can. FDA, CDC, and pharmaceutical manufacturers have successfully worked to redistribute available supplies of drugs, vaccines, immunoglobulins, and antisera, and to accelerate the production, testing, and release of new supplies to meet shortfalls. In certain emergencies they have resorted to modifying immunization schedules. When necessary, ad hoc coordination of activities of the NIH, CDC, FDA, DoD, and USAID has redirected resources to research and development efforts. In the vaccine area, coordination activities have been assigned by legislation to the Director of the National Vaccine Program Office. The FDA has limited authority under the Public Health Service Act to prepare biologic products for FDA or other agencies' use, although resources are required to utilize this authority. Both the National Vaccine Plan and the draft Pandemic Influenza Plan contain provisions that authorize payment for some production of vaccines against influenza and childhood diseases, for use in the United States. However, in most cases there is no U.S. Government mechanism to oversee procurement or production of emergency medical supplies.

There is a critical need for coordination and strategic planning to rethink and upgrade efforts for emergency preparedness for responding to disease outbreaks. Many groups are needed to participate in this effort, including CDC, NIH, and FDA; the DoD, the Department of State, and USAID; state and local health departments; and the private sector, including pharmaceutical trade organizations and research universities.

To fulfill this function, a designated U.S. Government group might identify potential suppliers of the drug or vaccine and enter into production agreements with one or more of them who might require

• Financial support to expand, re-establish, or setup a new production system;
  
• A commitment to use or purchase the product, once it is made and tested;
  
• Human and financial resources to conduct pre-clinical and clinical trials, if needed;
  
• Indemnification against liability;
  
• Government or contractual support to ensure that appropriate regulations were followed;
  
• Assistance and support in working with the governments of the countries where the problem exists to enable cooperation in development efforts and in the design and conduct of clinical trials.

• Access to emergency funding sources;
  
• The flexibility to by-pass the usual rules, such as Government contracting procedures;
  
• The ability to seek emergency legislative provisions, such as waivers or exemptions from export rules, or liability indemnification for the producer; and
  
• The cooperation and commitment of all relevant government agencies.

Strategic planning

To aid in this work, it is recommended that the Task Force

1. Determine which Governmental or non-governmental organizations participate in mobilizing emergency production of medical supplies by producing drugs, diagnostics, vaccines, or antisera, "stockpiling" nonperishable supplies, research, recommending where necessary and development of relevant medical products, providing capacity for emergency responses ("surge" capacity), anticipating the need for emergency production

2. Determine which known diseases are of highest concern, based on their likelihood of occurrence and potential impact, and consider whether vaccines, drugs, or diagnostic reagents are presently available to treat them, and if so, whether surge capacity exists for their production, distribution, and use.

• Using this information, the Task Force may consider how to

• Develop a coordinated Government mechanism for responding to infectious disease emergencies in other countries,
  
• Maintain an on-going dialogue with the private sector, and with researchers in industry as well as in academia, through a private sector subcommittee that includes representatives of the U.S.
  
• Prepare for outbreaks of "high priority" diseases by
- evaluating U.S. and foreign capacity for production of existing drugs and vaccines,
- recommending research to develop and evaluate new drugs, vaccines, and diagnostic reagents, where existing products are inadequate,
- anticipating the likelihood of occurrence through predictions based upon epidemiologic, environmental, climatic, and social data.

• Develop a program to promote the rapid development of standardized diagnostic tests for new and re-emergent diseases.
  
• Assess existing strategic plans for producing vaccines, drugs, and diagnostics for targeted diseases.
  
• Strengthen the capacity to produce medical supplies of limited market value, such as vaccines for Argentinian hemorrhagic fever and drugs for Lassa fever.
  
• Consider the utility of stockpiling certain priority vaccines, drugs, and diagnostics, based upon estimates of the likelihood of occurrence and potential impact. Recently, the NOAA has developed the capacity to forecast changes in climate due to El Nino currents, which can increase the incidence of infectious diseases. Predictive tools like this one may be useful in guiding stockpiling decisions.

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