Emerging Viral Infections

In addition to diseases such as HIV/AIDS, herpesvirus infections, and viral hepatitis, the Division of Antiviral Products reviews submissions and applications for antiviral products (including antiviral drugs and certain types of biologic products) directed against a range of infections that have recently emerged or re-emerged, or could emerge under certain conditions of public health crisis, as major causes of human illness. This category of emerging viral infections includes (but is not limited to) the following:

• Infections that may spread widely due to genetic changes in existing viral pathogens (such as novel strains of influenza);
• Infections appearing in new settings due to movement of human populations or of animal reservoirs  (such as West Nile virus or monkeypox);
• Infections newly recognized as causes of human disease (such as SARS or hantavirus pulmonary syndrome);
• Infections that are rare or nonexistent under normal circumstances but that could be sources of significant concern in the context of potential bioterrorism/biowarfare threats (such as smallpox, serious vaccinia infections complicating smallpox vaccination, or certain viral hemorrhagic fevers).

Approaches to drug development for emerging viral infections

Development of drugs for emerging viral infections poses distinctive challenges because many of these illnesses are rare but may be life-threatening, and have the potential to change rapidly in incidence and/or virulence, such that a serious public health threat could arise with little advance opportunity for study. Thus, although developing treatment and control measures is a high priority, the traditional sequence of nonclinical and clinical studies may be very difficult to implement. In order to facilitate progress without compromising scientific standards, careful attention to the following possible approaches may be desirable. Prospective sponsors should discuss these with the review division:

• Consideration of potential applicability to emerging infections during development of antivirals for other purposes;

• Assembly and analysis of treatment experience for related products and diseases that may have indirect relevance to the product and disease of interest;

• Prospective design of nonclinical studies (including shared discussion of planned animal studies across all review disciplines) to provide as much supplemental information as possible in support of potentially limited clinical data;

• Prospective design of clinical trials to maximize the amount of useful information that may be gained from sparse experience, and to address both the importance of adequately controlled and monitored trials and the constraints of study conduct under emergency conditions;

• Regulatory mechanisms for facilitation of timely interactions.

Sponsors seeking to develop antiviral drugs for emerging infections are urged to communicate with the Division as early in the development process as possible.  Typically the Pre-IND consultation program  will provide an appropriate mechanism for such early consultations.  For some drug development programs for emerging infections, repeated Pre-IND interactions may be desirable.   

Useful links for additional information on emerging infections and drug development

The following links provide access to additional information on general issues related to emerging viral infections and drug development for such infections. Listing is for informational purposes and may not imply endorsement.  Relevance of the listed resources will vary for specific development proposals. Potential sponsors or investigators are encouraged to contact the DAVP pre-IND contact  with questions.

• Pre-IND website (FDA/CDER/Office of Antimicrobial Products, including DAVP): Sponsors are urged to contact DAVP early in the development process to discuss the most efficient design and potential uses of nonclinical as well as clinical studies.
• FDA/CDER website for Influenza Antiviral Drugs and Related Information: This site provides summaries and links to information regarding influenza control public health measures, pandemic influenza preparedness, and approved drugs for treatment and prevention of influenza.
• FDA Counterterrorism website:  This site provides links to general information on counterterrorism-related activities at FDA.
• Selected FDA regulations, guidance, announcements/notices, and policy related to facilitating development of and access to drugs for serious life-threatening infections with limited therapeutic options, including (but not limited to) potential threat agents:
  
  • 21 CFR 312 Subpart E (312.80-312.88), Drugs Intended to Treat Life-threatening and Severely-debilitating Illnesses
  • 21 CFR 312.36, Emergency use of an investigational new drug
  • 21 CFR 312.34, Treatment use of an investigational new drug
  • Proposed Rule, Expanded Access to Investigational Drugs for Treatment Use [HTML] [PDF]
  • Final rule, Human Subject Protection; Foreign Clinical Studies Not Conducted Under an Investigational New Drug Application
  • Guidance, Emergency Use Authorization of Medical Products 
  • Draft Guidance for Industry, Vaccinia Virus — Developing Drugs to Mitigate Complications from Smallpox Vaccination 
  • Draft Guidance for Industry, Smallpox (Variola) Infection:  Developing Drugs for Prevention and Treatment
  • Draft Guidance for Industry, Influenza:  Developing Drugs for Treatment and/or Prophylaxis
  • Priority Review Policy
  • 21 CFR 314 Subpart H (314.500-314.560), Accelerated Approval of New Drugs for Serious or Life-Threatening Illnesses
  • 21 CFR 314 Subpart I (314.600-314.650), Approval of New Drugs When Human Efficacy Studies Are Not Ethical or Feasible (“Animal Rule”)
  • 21 CFR 601 Subpart H (601.90-601.95), Approval of Biological Products When Human Efficacy Studies Are Not Ethical or Feasible (“Animal Rule” for biologic products)
  • Concept Paper, Animal Models -- Essential Elements to Address Efficacy Under the Animal Rule [PDF]
  • Guidance for Industry, Fast Track Drug Development Programs - Designation, Development, and Application Review [PDF]

• National Institutes of Health, National Institute of Allergy and Infectious Diseases, Division of Microbiology and Infectious Diseases, Virology Branch, website with links to antiviral drug screening program: http://www.niaid.nih.gov/dmid/viral. Sponsors of antiviral drugs that might have applicability to treatment of emerging infections are encouraged to contact the NIH/NIAID/DMID/Virology Branch to discuss screening drugs for antiviral activity against emerging pathogens.
• Centers for Disease Control and Prevention Emerging Infectious Diseases website: http://www.cdc.gov/ncidod/diseases/eid/index.htm. This site contains information and additional links for a range of emerging infections and related topics.