Productive pre-IND interactions with FDA are important to the success of any drug development program, including infectious disease product development. The Pre-IND Consultation Program through the Office of Infectious Disease (OID), one of 27 review divisions within the Office of New Drugs, provides opportunities for makers of infectious disease products to engage with FDA by facilitating early communications between the Division of Antivirals or the Division of Anti-Infectives within OID and sponsors/investigators of potential new therapeutics – these products include drugs and therapeutic biologics for the treatment of bacterial, fungal, and viral infections (including SARS-CoV-2 infection). Early interactions allow for valuable FDA input prior to the accumulation of sufficient data for an IND submission, and allow the sponsor to solicit FDA feedback regarding the initial drug/biologic development plans, nonclinical IND-enabling study data needed to support moving the drug/biologic into clinical testing, and many other issues. In addition to these pre-IND interactions, FDA provides guidance documents regarding the development of therapeutics for some specific infectious diseases (see FDA Guidance for Industry: Chronic-Hepatitis-B-Virus-Infection-Developing-Drugs-for-Treatment; FDA Guidance for Industry: Chronic-Hepatitis-C-Virus-Infection—Developing-Direct-Acting-Antiviral-Drugs-for-Treatment-Guidance-for-Industry; and FDA Guidance for Industry: Vaccinia Virus – Developing Drugs to Mitigate Complications from Smallpox Vaccination). Here, we specifically discuss antiviral products at the pre-IND stage, and unique considerations for these products.
As with any development program, CMC, pharmacology, and toxicology programs* are necessary to move forward with an IND for antiviral products. Antiviral products additionally require nonclinical virology data to support the initial submission of an IND. Prior to the initiation of Phase 1 clinical studies, FDA recommends conducting nonclinical virology studies, including mechanism of action (MOA), antiviral activity in vitro, effects of serum protein binding on antiviral activity, and cytotoxicity and therapeutic indexes. These are discussed in more detail below.