Will the FDA accept an Investigational New Drug (IND) application for a novel drug containing preclinical evidence generated solely from "in silico" studies by 31 December 2035?

Started Jan 23, 2025 06:00PM UTC
Closing Feb 12, 2025 04:59AM UTC

During a drug’s development process, a company or organization producing the drug must submit an Investigational New Drug (IND) application to the FDA before it can begin clinical investigation (i.e., research trials on human subjects) (FDA). Currently, IND applications require preclinical experiments to be conducted in vitro (with cells, tissues, or biological molecules) and/or in vivo (with animal studies) to understand the drug’s mechanisms of action and level of toxicity before trials on human subjects begin (FDA).


In silico methods, which utilize computational data, facilitate virtual testing, reduce reliance on animal studies, and can replace human trials in specific cases where ethical concerns arise (Premier Research, DIA Global Forum). The emergence of artificial intelligence (AI) and machine learning (ML) is expected to accelerate the use of in silico methods for drug development (FDA). The FDA has supported the integration of in silico trials in drug development by recognizing their potential to enhance personalized treatment and streamline clinical trials. The FDA's initiatives include the Drug Development Tools Qualification program and the establishment of guidelines like Good Simulation Practices to standardize and validate these models (PubMed, The Clinical Trial Vanguard). This approach aims to accelerate drug approval processes while ensuring safety and efficacy (FDA, FDA). However, such in silico evidence is generally considered complementary rather than a full substitute for in vitro or in vivo preclinical evaluation.

Resolution Criteria:
This is an unscored question that closes for forecasting on 11 February 2025. Although this is an unscored question, we outline the theoretical resolution criteria here.

Relevant terms are defined below:
  • Novel drugs: new drugs never before approved or marketed in the U.S. (FDA)
  • In silico: simulated and/or “dry lab” studies conducted using computational data (e.g., bioinformatics, molecular docking) assisted by artificial intelligence (AI) and/or machine learning (ML) tools
  • In vitro: laboratory and/or “wet lab” studies conducted using physical biological matter (e.g., biochemical test kit assessing whether a drug can bind to an expected molecular drug target)
  • In vivo: animal studies (e.g., drug dosing to establish drug circulation times in an animal model)
This question would be resolved as “Yes” if either of the following conditions are met:
  • FDA announcements or press releases indicate that the FDA has approved an IND application for a novel drug intended for use in humans that contains experimental evidence solely from in silico (not in vitro or in vivo) preclinical evaluations.
  • Changes to regulations or IND application process are published in the Federal Register (e.g., 21 CFR Part 312 which outlines the requirements for IND applications) or on the FDA website allowing for in silico evidence to be submitted without in vitro or in vivo preclinical evaluations for IND applications for novel drugs intended for use in humans.

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