FDA Experience with Medical Countermeasures under the Animal Rule

The Food and Drug Administration issued a final rule in May 2002 to permit the Agency to approve drugs or license biological products on the basis of animal efficacy studies for use in ameliorating or preventing serious or life-threatening conditions caused by exposure to lethal or permanently disabling toxic biological, chemical, radiological, or nuclear substances. Only two drugs were approved in the first nine years of the “Animal Rule” despite massive investment by the federal government since 2001 to stimulate development of medical countermeasures to biological threats. This article therefore examines the Food and Drug Administration reviews made public after approval of those two drugs and the public discussion at the Agency's Anti-Infective Drugs Advisory Committee of one biological product under development under the Animal Rule. Despite the paucity of approved drugs or licensed biological products as medical countermeasures, several investigational drugs have been placed in the National Strategic Stockpile for use as medical countermeasures, if needed. 1. Introduction There is a risk in the post-September 11, 2001, world of chemical, biological, radiological, or nuclear attack on the United States, either on civilian populations or on military forces. To support the development of medical countermeasures (MCM) against such threats, the government has invested an estimated $54 billion in civilian spending from fiscal year 2001 through fiscal year 2010 [1]. Yet despite this massive investment, the United States lacks the range of MCM listed in the Health and Human Services Public Health Emergency MCM Enterprise Implementation Plan [2]. In 2002, the Food and Drug Administration (FDA) issued what has become known as the “Animal Rule,” intended to expedite the development of new drugs and biologic products as MCM to chemical, biological, radiological, and nuclear threats. The Animal Rule applies only to new drug or biologic products for which definitive human efficacy studies cannot be conducted because it would be unethical to deliberately expose healthy human volunteers to a lethal or permanently disabling toxic biological, chemical, radiological, or nuclear substance. Since the Animal Rule was issued, only two drug products for humans have been approved by the FDA on the basis of efficacy studies in animals. This paper summarizes the context in which the Animal Rule came into being, the regulatory provisions of the Animal Rule, and the publically-available information on how FDA has reviewed animal efficacy studies in support of drug or biologic