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How does FDA drug approval work? Full process explained
Stage 1: Preclinical research
Before any human testing, sponsors complete animal pharmacology + toxicology studies under FDA Good Laboratory Practice (GLP). For small molecules this includes pharmacokinetics, pharmacodynamics, and at least one rodent + one non-rodent species toxicology. For biologics, the burden is similar but uses species-relevant disease models. Typical duration: 3–6 years. ~95% of preclinical candidates fail to enter clinical trials.
Stage 2: IND filing
To start human trials, sponsors file an Investigational New Drug (IND) application — a comprehensive package including preclinical data, manufacturing CMC (Chemistry, Manufacturing, Controls), and proposed Phase 1 protocol. The FDA has 30 days to object; if silent, the IND becomes effective. ~30% of INDs receive clinical holds before activation.
Stage 3: Phase 1 — safety + PK
Phase 1 trials enroll 20–80 healthy volunteers (or patients for oncology) to establish maximum tolerated dose, pharmacokinetics, and initial safety signals. Duration: 1–2 years. ~65% of Phase 1 candidates proceed to Phase 2.
Stage 4: Phase 2 — proof of concept
Phase 2 trials enroll 100–500 patients with the target disease to demonstrate efficacy + further characterise safety. Endpoint typically a surrogate marker (tumour response, biomarker change) rather than the ultimate clinical outcome. Duration: 2–3 years. ~30% of Phase 2 candidates make it to Phase 3 — the biggest attrition step in the pipeline.
Stage 5: Phase 3 — pivotal
Phase 3 trials are typically 2 randomised controlled trials (or 1 large one) enrolling 1,000–5,000 patients to demonstrate efficacy + safety vs current standard of care or placebo. The primary endpoint is the clinical outcome the FDA cares about (overall survival, hospitalisation reduction, etc.). Duration: 3–5 years. ~58% of Phase 3 candidates achieve a positive readout.
Stage 6: NDA / BLA filing
After Phase 3, the sponsor files an NDA (small molecule) or BLA (biologic) with the full clinical + manufacturing dataset. The package can run 100,000+ pages. The FDA has 60 days to accept the filing, then 6 months (priority) or 10 months (standard) to issue a decision. The user fee per filing is ~$4M.
Stage 7: FDA review + approval
During the PDUFA review window, FDA reviewers analyse the data, potentially convene an Advisory Committee, and issue an approval, complete response letter (CRL), or tentative approval. ~88% of NDAs/BLAs that are filed are eventually approved (often after a CRL → resubmit cycle).
Stage 8: Post-marketing
After approval, sponsors run Phase 4 post-marketing trials (often a condition of approval), submit safety reports via FAERS, and may pursue label-expansion indications. The drug remains under active regulatory surveillance for as long as it's marketed.
FAQ
How long does FDA approval take in total?
Typically 10–15 years from discovery to launch. Preclinical 3–6 years, Phase 1 1–2 years, Phase 2 2–3 years, Phase 3 3–5 years, FDA review 6–10 months. Faster for breakthrough therapies, oncology, and rare disease.
What percentage of drugs get approved?
About 12–14% of drugs entering Phase 1 trials reach approval. Attrition is highest in Phase 2 (only ~30% advance to Phase 3) and Phase 3 (~58% succeed). Phase 1 has higher pass rates (~65%) because endpoint is safety, not efficacy.
What's the difference between NDA and BLA?
NDA (New Drug Application) is for small-molecule drugs reviewed under the Federal Food, Drug, and Cosmetic Act. BLA (Biologics License Application) is for biologics (proteins, antibodies, cell + gene therapy, vaccines) reviewed under the Public Health Service Act. Different statutory bases, different exclusivity periods (5 years for small molecule vs 12 years for biologic data exclusivity), different post-approval pathways.
What's a Complete Response Letter (CRL)?
A CRL is the FDA's "not yet" — it lists issues the sponsor must address before re-submission. Common reasons: manufacturing inspection findings, insufficient clinical data, safety questions, label-language disagreements. CRLs are not public unless the sponsor discloses them (which they almost always do via 8-K).