The purpose of this guidance is to assist sponsors in the clinical development of drugs for
treatment or prevention of smallpox (variola virus) infection. Clinical efficacy trials of drugs
for treating or preventing smallpox are not feasible and challenge studies in healthy subjects are unethical; therefore, drugs for these indications should be developed and approved under the regulations commonly referred to as the Animal Rule (21 CFR part 314, subpart I, for drugs and 21 CFR part 601, subpart H, for biologics). This guidance serves as a focus for continued discussions among the Division of Antiviral Products (DAVP), pharmaceutical sponsors, the academic community, and the public.
This guidance focuses on drugs that are expected to inhibit variola virus replication. Although antiviral drugs are the primary focus of this guidance, therapeutic proteins or monoclonal antibodies also may be eligible for evaluation under the Animal Rule. Sponsors interested in developing small molecules, therapeutic proteins, or monoclonal antibodies for use against smallpox are encouraged to discuss their approach with the FDA as early as possible in development and to communicate with the FDA through the Pre-IND Consultation Program…