Infectious diseases know no boundaries. Our world is faced with constantly emerging and naturally occurring new threats, from pandemic influenza to novel pathogens like the SARS coronavirus. Simultaneously, we must be cognizant of the fact that our world is unstable; thus, we are susceptible to chemical, biological, radiological, and/or nuclear attacks as well. We must prepare for a broad range of potential threats, both natural and deliberate — from anthrax to smallpox to influenza to something new or unexpected. Moreover, major, devastating infectious diseases, such as TB and malaria, and even common bacteria such as Staphylococci, are increasingly resistant to available treatments, threatening people in all nations.
Current approaches to the development and evaluation of needed vaccines, diagnostics and treatments are not sufficient to quickly and fully meet global and domestic needs. The development of these needed medical countermeasures (MCM) has yet to take full advantage of scientific innovations in basic science or in product development — manufacturing and evaluation that could transform preparedness and redefine global health.
What has FDA done?
For years, FDA has been central to the identification and development of vaccines to protect against each new strain of influenza on an annual basis. A successful public-private partnership during the 2009 H1N1 influenza pandemic brought about the development and approval of safe and effective vaccines in record time. These and the more detailed example below are a few examples of regulatory science efforts ongoing at the FDA.
- Prevented contamination of the nation’s blood supply
West Nile virus is an illness spread by mosquitoes which results in asymptomatic infection, fever, meningitis or encephalitis and/or death. In 2002, a total of 4,156 cases of West Nile virus infections were reported. This number more than doubled to 9,862 in 2003, before gradually tapering off to 720 cases in 2009. FDA and CDC were also concerned that the virus could potentially be transmitted via blood transfusion and organ transplantation. In September 2002, such transmission was confirmed. As the health care system worked to treat those infected with the potentially deadly disease, FDA worked intensively with CDC and the blood and diagnostics industries to rapidly respond to the threat to blood safety, including employing strong regulatory science to develop the standardized reagents needed for test development. This effort was pivotal in supporting the rapid nationwide implementation of blood donation testing for West Nile Virus and helped ensure that the nation’s blood supply remained safe, preventing a potentially serous epidemic of transfusion transmitted infection.
What can FDA do with increased investment in regulatory science?
A committed, continuous investment in regulatory science is essential to producing medical countermeasures against public health threats. As noted in the Public Health Emergency Medical Countermeasures Review, "Enhancement and ultimate application of updated regulatory science and scientific review capacity will help strengthen the MCM regulatory process and thus streamline the MCM development process. FDA will undertake a new initiative … designed to focus on augmenting the tools used to assess the safety, efficacy, and quality of medical products, with a particular focus on MCMs, and to get them from concept through the approval process efficiently."
- New approaches to evaluate product efficacy
It is not always possible to test whether a vaccine or treatment will work against a new or emerging infectious disease, or against a terrorist threat, because the threat may be rare — or even nonexistent — at the time the therapy needs to be developed. Animal testing is often the only available option, but many diseases lack even good animal models, and animal studies are technically difficult to conduct and typically limited in size. Therefore, regulatory science is needed to develop and validate improved predictive models.
Regulatory science can also support the identification and validation of surrogate measures of product efficacy. For example, FDA’s definition and acceptance of a serum hemagglutination inhibition antibody titer, which helps predict the efficacy of influenza vaccines, took years off the time required to approve new flu vaccines, and, as a result, helped to double the number and capacity of U.S. licensed flu vaccine makers. Such biomarkers (e.g. responses in blood tests, other measurements, or medical images) that predict efficacy are not yet available for most terrorism threats, emerging pathogens or major global infectious diseases. Efforts to develop, refine and validate new biomarkers can lower development costs and improve and speed the development of safe and effective products for unmet public health needs.
- More flexible and agile approaches to product development and manufacturing
Knowledge of genetic sequences can enable us to produce products such as DNA and recombinant vaccines, or needed treatments and diagnostic tests, more quickly and safely without using the pathogen in manufacturing.
The use of platform technologies of this sort may offer the potential to scale up production more rapidly. For example, several technologies could potentially allow production of large amounts of new influenza vaccines for a pandemic in weeks, rather than months. Platform technologies may also be applicable across broader ranges of products. For example, the same virus-like particle, live vector, DNA vaccine or recombinant protein expression system could be used as the basis to rapidly develop and produce different, distinct vaccines intended to protect against illnesses such as flu, plague, SARS or TB. Even stronger commonalities apply across technologies that can be used for detection or diagnosis, such as high-throughput assays for antibody, antigen and nucleic acid detection.
Evaluating such multi-use technologies and products requires advances in regulatory science — including new methodologies for measuring product quality, potency, safety and effectiveness. FDA guidance and engagement with partners will be critical to make sure products can move from the future into the present.
- Validation of improved potency and rapid sterility assays
Modernized, rapid testing methods are needed to support more rapid deployment of life-saving products in an emergency. FDA must work to develop and implement rapid, sensitive, high throughput methodologies to detect, identify and investigate microbial or other product contaminants to elevate the nation’s public health preparedness to emerging infectious diseases and other natural or man-made threats.
- Methods to improve product stability
Regulatory science can be applied to find ways to enhance the shelf life of products or to avoid the need for cold storage, which is required for many drugs and vaccines. These improvements may be of critical importance in an emergency and are important cost-saving tools for fighting disease globally.
- New statistical approaches to assessing efficacy where data Is limited
Just as laboratory sciences have advanced, biostatistical approaches are rapidly evolving. New methods that provide reliable information from more limited data sets can be crucial during an emerging disease outbreak.
- Cell culture and in silico modeling of safety and efficacy
The ability to predict safety or efficacy in a test tube or in silico, through computer modeling can save time and resources; may result in safer, more targeted therapies; and is critical when a disease is rare or when there is insufficient time to complete clinical trials.
- New point-of-care diagnostics
Application of novel technologies, such as nanotechnology, is needed to enhance our ability to detect and diagnose disease at the point of care during an emergency. This could also enable development of tests to immediately detect drug resistance during a public health emergency, so that patients are sure to get treatment that works.
- New dosing forms and delivery methods
Response time in an emergency can be everything. New product formulations and deliveries, such as needle-free systems, are needed for more nimble distribution and use of products and to allow their self-administration, where appropriate.
- Real-time assessment of product performance
Application of information technology tools, advanced biostatistics methods and health data mining are needed to assess product effectiveness and safety during emergencies. The unprecedented safety monitoring systems put in place for 2009 H1N1 vaccination program were an example of real-time assessment in action. FDA should work to develop a bioinformatics database for emerging infectious diseases that are potential threats to the blood supply.
- Enhanced risk assessment and communication
Advances in the science of risk assessment and risk communication are needed to provide clear, accurate and understandable information to the public, enhance public confidence and empower people to make wise decisions and protect their health and their communities.