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Smallpox (Variola Virus) Infection: Developing Drugs for Treatment or Prevention Guidance for Industry

FinalCenter for Drug Evaluation and Research11/18/2019

Description

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.

Scope & Applicability

Product Classes

3
Monoclonal Antibodies

Circumstance where a mass balance study might not be recommended

Smallpox Vaccine

Vaccine used in postevent vaccination programs and for laboratory personnel

Therapeutic Proteins

Proteins that reduce proinflammatory cytokines and affect CYP enzyme expression

Stakeholders

4
Sponsor

Entity responsible for submitting applications under section 524B

Laboratory and Health Care Personnel

Individuals at risk for occupational exposure

Advisory Committee on Immunization Practices

Provides recommendations for universal Hepatitis B vaccination

Antiviral Drugs Advisory Committee

Met in 2011 to discuss variola virus infection drug development

Regulatory Context

Attributes

2
Expiration Dating Period

CMC changes after tentative approval; shelf-life period supported by stability data; proposing to extend the expiration dating period for the drug product

Mortality

Primary endpoint for efficacy studies

Identified Hazards

Hazards

3
Bioterrorism

Potential use of variola virus as a weapon

Occupational Exposure

Safety finding requiring reporting; Reports of occupational exposure should be followed up

Mitochondrial Toxicity

Risk associated with small molecule inhibitors like nucleoside analogues

See Also (8)

Smallpox (Variola Virus) Infection: Developing Drugs for Treatment or Prevention Guidance for Industry | Guideline Explorer | BioRegHub