Lessons learned from a review of the development of selected vaccines. National Vaccine Advisory Committee.

BACKGROUND: Although the vaccine research and development network in the United States remains vibrant, its continued success requires maintaining harmonious interaction among its many components. Changing one component is likely to affect the system overall. An examination of case studies of the development of selected vaccines would allow an examination of the network as a whole. This article presents conclusions drawn from the case study review undertaken. OBJECTIVE: Successful development of vaccines is a time-intensive process requiring years of commitment from a network of scientists and a continuum of regulatory and manufacturing entities. We undertook this work to shed light on how well the vaccine development system in the United States performs. METHOD: The National Vaccine Advisory Committee examined the research and development pathways of several vaccines that reached licensure expeditiously (hepatitis B vaccine, Haemophilus influenzae type b conjugate vaccines); some that became licensed only after considerable delay (oral typhoid Ty21a vaccine, varicella vaccine); some that are at the point of imminent or recent licensure (reassortant Rhesus rotavirus vaccine, which was licensed by the Food and Drug Administration on August 30, 1998) or near submission for licensure (intranasal cold adapted influenza vaccine); and one for which clinical development is slow because of hurdles that must be overcome (respiratory syncytial virus vaccines). RESULTS: Some common themes emerged from the reviews of these vaccine "case histories": the expediting influence of a strong scientific base and rationale; the need for firm quantitation of disease burden and clear identification of target populations; the critical role played by individuals or teams who act as "champions" to overcome the inevitable obstacles; availability of relevant animal models, high-quality reagents and standardized assays to measure immune response; the absolute requirement for well designed, meticulously executed clinical trials of vaccine safety, immunogenicity, and efficacy; postlicensure measurements of the public health impact of the vaccine and a track record of the vaccine's safety and acceptance with large-scale use; and the critical need for international collaborations to evaluate vaccines against diseases of global importance that are rare in the United States (eg, typhoid fever). It was clear that the critical step-up from bench scale to pilot lots and then to large-scale production, which depends on a small group of highly trained individuals, is often a particularly vulnerable point in the development process. CONCLUSIONS: One fundamental lesson learned is that within the varied and comprehensive US vaccine development infrastructure, multiple and rather distinct paths can be followed to reach vaccine licensure. The National Vaccine Advisory Committee review process should be conducted periodically in the future to ascertain that the US vaccine development network, which has been enormously productive heretofore and has played a leadership role globally, is adapting appropriately to ensure that new, safe, and efficacious vaccines become available in a timely manner.

Adult immunizations: how are we doing?

Physicians seldom ask adult patients about basic immunizations or seek to determine whether the patient's occupation, lifestyle, or travel may warrant additional vaccine coverage. Yet more than 30,000 lives could be saved every year in the United States if adult immunization recommendations were implemented. Strategies for improving delivery are reviewed and information on specific vaccines is updated.

Airborne nosocomial infection: a contemporary perspective.

The history of airborne nosocomial infections is reviewed, and current beliefs about such infections are placed into their historical context. Possible sources, both animate and inanimate, of airborne nosocomial infections in the hospital environment are identified. Viruses, bacteria, and fungi that have been important causes of airborne nosocomial infections in the past are discussed, and examples of key studies that have confirmed an airborne route of transmission are presented. Where relevant, measures that have been used to control airborne transmission of nosocomial pathogens are discussed. Although outbreaks of airborne nosocomial infection have been uncommon, airborne transmission appears to account for about 10% of all endemic nosocomial infections.

Current immunization practices in adults.

Can the successes of pediatric immunization programs be matched in adults? The question relates both to infections due to waning immunity and to those primarily acquired in adulthood. It is given urgency by rising prevalence of vaccine-preventable diseases in adults. Strategies with available vaccines are reviewed, and vaccines in development are discussed.

Respiratory tract infections. Goals for 1995.

Goals to be identified for 1995, a decade hence, in the prevention, diagnosis, and management of respiratory tract infections may conveniently be divided into diagnostic goals and goals in therapy and prophylaxis. Major diagnostic goals for bacterial, viral, and mycoplasmal infections of the respiratory tract focus on the development of systems to identify microbial components, such as specific antigens or segments of DNA, using monoclonal antibody techniques or DNA probes for hybridization. Sputum cultures, in the traditional sense, should ultimately become obsolete. Management goals include the development of algorithms to identify patients who should be hospitalized, in contrast to those who can safely be treated on an outpatient basis. New antibiotic drug development should include drugs active against methicillin-resistant staphylococci, broad-spectrum beta-lactam drugs that are orally active against gram-negative bacilli, and drugs that can be used parenterally on a once-daily basis in settings other than the acute care hospital. There are certainly needs to enhance the present spectrum of antiviral drugs and to develop therapeutically useful immunomodulators. There are promising prospects for vaccine development, including live attenuated influenza virus vaccine, parainfluenza virus vaccine, respiratory syncytial virus vaccine, and a Mycoplasma pneumoniae vaccine. With major research support, such vaccines could possibly be fully developed by 1995. Finally, of greatest importance is the need to achieve greater utilization of existing vaccines, that is, inactivated influenza vaccine and the current 23-valent pneumococcal vaccine. A legitimate goal for 1995 would be to achieve 70 percent or greater utilization of these vaccines within the recommended target populations.