Preclinical Development

Preclinical development (also called nonclinical development) is the stage of drug or biologic development that runs between candidate selection/lead optimization and the filing of an Investigational New Drug (IND) application — the period in which a sponsor generates the animal and in vitro pharmacology, toxicology, and pharmacokinetic (ADME) data needed to establish a reasonable basis for testing the candidate safely in humans, alongside early manufacturing and formulation work.

Why “preclinical trials” is a misnomer

Searchers often look for “preclinical trials,” but the phrase is technically inaccurate, and the distinction is not just pedantic — it maps onto two entirely different regulatory oversight systems. A clinical trial is, by definition, a study conducted in human participants: it requires informed consent, Institutional Review Board (IRB) approval, and (once an IND is open) conduct under ICH GCP (Good Clinical Practice). Preclinical work never involves human subjects at all — it uses animal models and in vitro/in silico systems, overseen by an IACUC (Institutional Animal Care and Use Committee) rather than an IRB, and the pivotal safety studies are conducted under Good Laboratory Practice (GLP) (21 CFR Part 58) rather than GCP.

The precise terms are preclinical studies or nonclinical studies — FDA’s own regulations consistently use “nonclinical laboratory study” (see 21 CFR Part 58) and “nonclinical studies” (21 CFR 312.23) rather than “trial.” “Trial” is reserved, throughout FDA regulation and in ordinary research-administration usage, for studies in human participants. If a searcher lands here looking for “preclinical trials,” what they almost always mean is preclinical development, or the specific studies within it — this page covers both.

What preclinical development actually includes

There is no single regulation that defines “preclinical development” as one bounded checklist — it is a lifecycle-stage concept, and the specific package of studies a sponsor needs is scaled to the candidate’s modality, indication, and intended clinical trial design (per the ICH M3(R2) framework FDA has adopted as guidance). In practice, preclinical development for a typical small-molecule or biologic candidate spans:

• Pharmacology studies — establishing the candidate’s mechanism of action and demonstrating proof-of-concept activity (e.g., efficacy in an animal disease model) before committing further resources to the candidate.
• GLP toxicology and safety pharmacology — repeat-dose toxicology in two species (typically one rodent, one non-rodent) and a safety pharmacology core battery assessing cardiovascular, CNS, and respiratory effects, run under GLP for the pivotal studies that will support the IND. See CASRAI’s IND-Enabling Studies entry for the full package (including genotoxicity and ADME/PK study types) in detail.
• Pharmacokinetics, toxicokinetics, and ADME studies — characterizing absorption, distribution, metabolism, and excretion in animal models, used with the toxicology findings to derive a no-observed-adverse-effect level (NOAEL) and a proposed human starting dose.
• Formulation and early manufacturing (CMC) work — developing a stable, reproducible dosage form and a manufacturing process that can supply both the nonclinical studies and, eventually, the first human trial, generally consistent with phase-appropriate Good Manufacturing Practice (GMP) expectations for early-phase investigational material.

The output of this stage is the pharmacology/toxicology section of the IND itself (21 CFR 312.23(a)(8)) — the data package an FDA reviewer relies on to decide, within the standard 30-day IND review clock, whether it is reasonably safe to allow the sponsor to begin dosing human participants.

Where preclinical development sits in the overall pipeline

Preclinical development is a specific, bounded stage between two others, and confusing it with either neighbor is a common source of miscommunication in cross-functional research-administration settings:

• Before it: discovery and lead optimization — open-ended, exploratory identification and refinement of candidate compounds or biologics, with no specific regulatory submission yet in view. GLP and formal IND-enabling obligations do not attach at this stage.
• Preclinical development itself: the candidate has been nominated for advancement, and the sponsor is generating the nonclinical safety/pharmacology package and building the manufacturing process needed to support an IND filing.
• After it: once the IND is active, the sponsor moves into clinical development — see CASRAI’s Clinical Trial Phases guide for how Phase 1 through Phase 4 are structured and regulated. Some nonclinical studies (e.g., carcinogenicity, reproductive toxicology) may continue in parallel with early clinical phases, but the human dosing itself marks the transition out of preclinical development.

Frequently asked questions

Is “preclinical trial” ever correct usage?

Not in a regulatory sense. FDA regulation and standard research-administration usage reserve “trial” for studies in human participants. The correct terms are “preclinical study” or “nonclinical study.” The phrase “preclinical trials” is common in casual and even some marketing usage, but it is a misnomer worth correcting in any protocol, grant, or regulatory document.

Does preclinical development always involve animal testing?

Most preclinical safety packages still rely on animal toxicology studies, particularly for the pivotal GLP studies feeding into an IND, but this is an area of active regulatory change: FDA released an April 2025 roadmap describing a multi-year effort to reduce reliance on animal testing in preclinical safety studies, beginning with monoclonal antibodies and other biologics and extending later to small-molecule candidates, as non-animal methods (NAMs) such as organ-on-chip and computational models are validated. Current regulation still permits and, for many pivotal studies, expects animal data; sponsors should not assume a non-animal package will be accepted without confirming current FDA expectations for their specific candidate class.

Who oversees preclinical development at a research institution?

Oversight is split by function, not by a single committee: the IACUC reviews and approves the animal-use protocol itself (animal welfare, husbandry, humane endpoints), while GLP compliance (21 CFR Part 58) — the Study Director, an independent Quality Assurance Unit, SOP-driven documentation — governs whether the resulting data is acceptable to FDA for an IND submission. A study can be fully IACUC-approved and still fail to meet GLP if it wasn’t run under a GLP-compliant protocol and quality system.

How long does preclinical development take?

There is no fixed duration — it depends heavily on the candidate’s modality, target, and how much pharmacology/proof-of-concept work is still needed when the candidate is nominated. The GLP toxicology, safety pharmacology, and ADME studies alone typically take many months to run in sequence or parallel once initiated, making the IND-enabling portion of preclinical development one of the longer, more resource-intensive stretches of the overall drug-development timeline.

Related CASRAI resources

• IND-Enabling Studies — the specific GLP toxicology, safety pharmacology, and PK/ADME package required before an IND filing
• Good Laboratory Practice (GLP) — the quality-system regulation governing pivotal nonclinical safety studies
• IACUC — the committee overseeing animal-use protocols during preclinical work
• Good Manufacturing Practice (GMP) — phase-appropriate manufacturing-quality requirements
• Clinical Trial Phases — what follows preclinical development once an IND is active
• Clinical Research Administration — cluster hub

References

• 21 CFR Part 58 — Good Laboratory Practice for Nonclinical Laboratory Studies (eCFR)
• 21 CFR 312.23 — IND content and format, including the pharmacology/toxicology section
• ICH M3(R2) — Nonclinical Safety Studies for the Conduct of Human Clinical Trials and Marketing Authorization for Pharmaceuticals
• FDA, “Roadmap to Reducing Animal Testing in Preclinical Safety Studies” (April 2025)