An IND (Investigational New Drug application) is required before human trials can begin, for any modality. After Phase 3, a sponsor files for marketing approval: an NDA (New Drug Application) for a small-molecule drug, or a BLA (Biologics License Application) for a biologic. The IND gate is modality-agnostic and comes first; the NDA-versus-BLA split is the modality-specific one that comes later.
IND, NDA, and BLA at a glance
| IND | NDA | BLA | |
|---|---|---|---|
| What it is for | Permission to begin human clinical trials | Marketing approval for a small-molecule drug | Marketing approval for a biologic |
| Applies to which modality | Any modality (small molecule or biologic) | Small-molecule drugs | Biologics: mAbs, cell therapy, gene therapy, vaccines |
| When it is filed | Before Phase 1 | After Phase 3 | After Phase 3 |
| FDA review center | Not applicable at this stage | CDER (Center for Drug Evaluation and Research) | CBER (Center for Biologics Evaluation and Research) |
| Legal basis | FD&C Act | FD&C Act | PHS Act |
What is an IND (Investigational New Drug application)?
An IND is the FDA application required before a sponsor can begin human clinical trials. It covers the preclinical safety data generated so far and the plan for the trial itself. The IND gate applies uniformly regardless of modality, a small-molecule program and a biologic program both need an active IND before Phase 1 can start.
Because the IND sits at the transition between preclinical work and the first human trial, an IND filing or clearance is one of the earliest and clearest indicators that a program is moving from research into active clinical development, and that the sponsor will soon need the outside support, clinical operations, regulatory, that a clinical-stage program typically requires.
What is an NDA (New Drug Application)?
An NDA is the FDA marketing-approval application for a small-molecule drug. It is filed after Phase 3, once a sponsor has the confirmatory efficacy and safety data needed to support approval, and it is reviewed by the Center for Drug Evaluation and Research (CDER) under the Food, Drug, and Cosmetic Act.
What is a BLA (Biologics License Application)?
A BLA is the FDA marketing-approval application for a biologic, including monoclonal antibodies, cell therapy, gene therapy, and vaccines. Like an NDA, it is filed after Phase 3. Unlike an NDA, it is reviewed by the Center for Biologics Evaluation and Research (CBER), under the Public Health Service Act rather than the Food, Drug, and Cosmetic Act.
Why the IND gate and the NDA/BLA split are tracked separately
The IND gate and the NDA/BLA split are tracked separately because they mark two entirely different stages of a program's life, separated by the full clinical trial process. The IND gate is modality-agnostic: it is the same "may this sponsor begin human trials" question regardless of what kind of product is being tested. The NDA-versus-BLA choice is the modality-specific one, and it is decided by what the product actually is, a small molecule goes through an NDA, a biologic goes through a BLA, not by the sponsor's size, therapeutic area, or development timeline. Treating an IND filing and an NDA or BLA filing as the same kind of event misses that distinction. See the life science GTM glossary for how these filings fit alongside the broader clinical trial phase vocabulary.