What are Medical Countermeasures?
“Medical countermeasures, or MCMs, are FDA-regulated products (biologics, drugs, devices) that may be used in the event of a potential public health emergency stemming from a terrorist attack with a biological, chemical, or radiological/nuclear material, a naturally occurring emerging disease, or a natural disaster.” (From the FDA website)
Product Development Under the Animal Rule
When developing a medical countermeasure, testing for efficacy in humans would not be ethical or feasible. The FDA therefore developed regulations for approval of these products based on well-controlled animal studies. Results from those animal studies have to show that the drug or biologic is reasonably likely to produce a clinical benefit in humans. These regulations are commonly referred to as the Animal Rule.
Since the establishment of the Animal Rule in May 2002, statistical methodologies have been developed to bridge the gap between animal models and predicting efficacy in humans. BSSI has many years of experience supporting clients in the development of MCMs (drugs, biologics and medical devices) and has been developing new analytical strategies to support the approval process under the Animal Rule. The challenges are numerous and include:
- Development of well-characterized animal models:
- Study design and power analysis
- Median lethal dose estimation
- Toxicokinetics studies
- Validation for assays measuring correlative of protection, potency, and toxicity
- Endpoints established in the animal studies have to be clearly tied to the desired benefit in humans
- Kinetic and pharmacodynamic analyses in animals and humans are necessary to determine a “humanized” dose
- Pharmacokinetics/Pharmacodynamics analyses
- Non-inferiority evaluation of effective doses