Investigational Medicinal Product (IMP)

An Investigational Medicinal Product (IMP) is the EU and UK clinical-trials regulatory term for a medicinal product — a drug, biologic, or matching placebo — that is being tested, or used as a reference, in a clinical trial. The definition also captures an already-authorised product used differently than its approved marketing authorisation: in a different formulation or packaging, for an indication it isn’t approved for, or to gain further information about an approved use. “IMP” is a naming convention, not a functionally distinct category from the US FDA’s “investigational new drug” — the two labels describe essentially the same class of trial material under different regulatory regimes, which is where most of the practical confusion for researchers and research administrators moving between US and EU/UK trial contexts actually comes from.

This entry focuses on what makes a product an IMP and how the term maps across the US and EU/UK regulatory vocabularies. For the operational side of managing that product once it exists — GMP manufacturing, packaging and blinding, cold-chain logistics, and site-level drug accountability — see CASRAI’s guide to Clinical Trial Supply Management, which this entry deliberately does not duplicate.

What makes a product an IMP (operational definition)

Under Regulation (EU) No 536/2014, Article 2(2)(5), an IMP is “a medicinal product which is being tested or used as a reference, including as a placebo, in a clinical trial.” The UK’s own domestic framework — the Medicines for Human Use (Clinical Trials) Regulations 2004 (SI 2004/1031, as amended) — uses materially the same definition and the same “IMP” term; the UK never adopted Regulation 536/2014 itself, since it left the EU before the Regulation became applicable (31 January 2022), so UK trials are governed by this separate domestic instrument rather than the EU Regulation directly, even though the underlying IMP concept is the same.

A product counts as an IMP when it falls into one of these categories:

• The test article itself — the drug, biologic, or device-delivered substance whose safety or efficacy the trial is actually investigating.
• A comparator or placebo — the definition explicitly includes a product “used as a reference…including as a placebo,” so a matching placebo or an active comparator arm is an IMP in its own right, not a separate category.
• An already-authorised product used outside its approved terms — a marketed medicine used, formulated, or packaged differently than its marketing authorisation, used for an indication outside that authorisation, or used to gather further information about an already-approved use.

The internationally harmonised counterpart to this definition is ICH E6(R2) Good Clinical Practice, §1.33, which defines “Investigational Product” in near-identical terms: “a pharmaceutical form of an active ingredient or placebo being tested or used as a reference in a clinical trial, including a product with a marketing authorization when used or assembled (formulated or packaged) in a way different from the approved form, or when used for an unapproved indication, or when used to gain further information about an approved use.” The EU/UK “IMP” is, in substance, the region-specific regulatory label for the same concept ICH GCP calls “investigational product” — see CASRAI’s ICH GCP (Good Clinical Practice) entry for the wider standard.

The terminology bridge: EU/UK “IMP” vs. the US “investigational new drug”

This is the point that most often trips up researchers and research administrators working across US and EU/UK trial contexts: the US regulatory system does not use the word “IMP” at all. Under 21 CFR 312.3, FDA defines “investigational new drug” as “a new drug or biological drug that is used in a clinical investigation,” and the same section states that “investigational drug” and “investigational new drug” are deemed synonymous throughout 21 CFR Part 312. In practice, US researchers, sponsors, and IRBs almost always shorten this to “IND,” “investigational drug,” or “study drug” — not “IMP.”

The three vocabularies line up as follows:

• EU: “Investigational medicinal product (IMP)” — Regulation (EU) No 536/2014, Article 2(2)(5). Governs the Clinical Trial Application (CTA) and the Investigational Medicinal Product Dossier (IMPD) submitted to national competent authorities.
• UK: “Investigational medicinal product (IMP)” — Medicines for Human Use (Clinical Trials) Regulations 2004 (SI 2004/1031, as amended), regulated by the MHRA. Same term as the EU, different (domestic) legal instrument.
• US: “Investigational new drug” / “investigational drug” — 21 CFR 312.3, governed via the Investigational New Drug (IND) application process at 21 CFR 312.23. FDA guidance and correspondence do not use “IMP” as a defined term.
• ICH GCP (harmonised, cited by both regions): “Investigational product” — ICH E6(R2) §1.33 / E6(R3). This is the neutral term that appears in globally-written protocols, investigator’s brochures, and informed consent language precisely because it doesn’t commit the document to either region’s statutory vocabulary.

The practical consequence: a multi-region trial protocol will often default to the ICH GCP term “investigational product” as neutral language usable everywhere, but the actual regulatory filings diverge by design — a US IND application will never say “IMP,” and an EU/UK Clinical Trial Application and its supporting IMPD will never say “investigational new drug.” A research administrator managing the same compound across both filing types needs to track both terms correctly, not treat one as a stand-in for the other in regulatory correspondence.

Worked examples

• A monoclonal antibody dosed in a Phase 2 oncology trial running at both US and EU/UK sites: the identical physical drug product is described as the “investigational new drug” in the US IND application (21 CFR 312.3) and as the “IMP” in the EU Clinical Trial Application and its supporting IMPD — one product, two regulatory labels, tracked separately in each filing.
• A matching placebo, manufactured and packaged to be visually indistinguishable from the active treatment, used as the comparator arm in a randomised double-blind trial: the placebo itself is an IMP under Regulation (EU) No 536/2014 Article 2(2)(5), which explicitly extends the definition to a product “used as a reference…including as a placebo.”
• An already-marketed antihypertensive drug being tested at a different dose for a new cardiology indication: even though the product already holds a marketing authorisation for its original use, it becomes an IMP for the purposes of this specific trial because it is being used, in this protocol, for an indication and dose outside that authorisation.

What is not an IMP (counter-examples)

• A rescue or background medication administered per the trial protocol but not itself the object of investigation — for example, a corticosteroid given for symptom management during an oncology trial — is an auxiliary medicinal product (AxMP) under Regulation (EU) No 536/2014 Article 2(2)(8), a defined category distinct from an IMP precisely because it is used for the needs of the trial but not tested or used as a reference. (This category was called a “non-investigational medicinal product,” or NIMP, under the older EU Clinical Trials Directive 2001/20/EC; “auxiliary medicinal product” is the current Regulation 536/2014 terminology and the one in active use.)
• An already-marketed drug a participant continues taking for an unrelated, pre-existing condition, strictly per its approved label and outside anything the trial protocol specifies, is ordinary concomitant medication — not an IMP and not an auxiliary medicinal product either, since it isn’t part of the trial’s defined product set at all.

Related terminology

• IMPD (Investigational Medicinal Product Dossier) — the EU/UK regulatory submission summarising an IMP’s quality, manufacture, and control data, plus available non-clinical and clinical information, submitted alongside a Clinical Trial Application. There is no direct US equivalent document with the same name; the closest functional counterpart is the Chemistry, Manufacturing, and Controls (CMC) section of a US IND application.
• Auxiliary medicinal product (AxMP) — a trial-protocol medicinal product that is not itself under investigation (see counter-examples above); formerly “non-investigational medicinal product” (NIMP).
• Qualified Person (QP) — the EU role that must certify an IMP batch was manufactured to GMP and specification before it can be released to a trial site; see CASRAI’s Clinical Trial Supply Management guide for the full release and distribution mechanics.
• Investigational New Drug (IND) application — the US FDA submission (21 CFR 312.23) a sponsor must have in effect before starting a US clinical trial; note this term does double duty in US usage, referring both to the drug product itself (21 CFR 312.3) and, colloquially, to the application authorising its investigational use — a usage pattern “IMP” does not share, since the EU/UK submission is called a Clinical Trial Application, not an “IMP application.”

Related CASRAI resources

• Clinical Trial Supply Management — GMP manufacturing, packaging/blinding, cold-chain logistics, and site-level drug accountability for IMPs across the trial lifecycle.
• Good Manufacturing Practice (GMP) — the quality framework IMP manufacturing operates within.
• What Is a Clinical Trial? The NIH Definition Explained — how “clinical trial” itself is defined, upstream of what counts as an IMP within one.
• Clinical Trial Phases — how IMP-related obligations (e.g. phase-appropriate GMP) scale across a trial’s phases.
• ICH GCP (Good Clinical Practice) — the harmonised standard whose “investigational product” term underlies both the EU/UK “IMP” and US usage.
• Randomized Controlled Trial (RCT) — the trial design in which an IMP is most often compared against a placebo or active comparator.
• Clinical Research Administration — CASRAI’s cluster hub for clinical-research operations and compliance content.

Frequently asked questions

Is an IMP the same thing as an IND?

They refer to the same underlying category of drug product — a medicinal product under investigation in a clinical trial — but “IND” does double duty in US usage that “IMP” doesn’t share. “IND” is both the FDA’s term for the drug itself (21 CFR 312.3, “investigational new drug”) and the common shorthand for the Investigational New Drug application (21 CFR 312.23) a sponsor files before starting a US trial. The EU/UK equivalent regulatory submission is called a Clinical Trial Application, supported by an Investigational Medicinal Product Dossier (IMPD) — there is no “IMP application” as such.

Is a placebo an IMP?

Yes. Regulation (EU) No 536/2014, Article 2(2)(5) explicitly defines an IMP as a product “being tested or used as a reference, including as a placebo,” so a trial’s placebo arm is itself an IMP under EU/UK law, subject to the same GMP, labelling, and accountability requirements as the active product it’s blinded against.

What is the difference between an IMP and an auxiliary medicinal product?

An IMP is the product under investigation, or used as its reference/placebo. An auxiliary medicinal product (AxMP) — formerly called a non-investigational medicinal product (NIMP) — is a different medicinal product the protocol requires (e.g. a rescue or background therapy) that is not itself being tested or used as a comparator. Regulation (EU) No 536/2014 defines them separately, at Article 2(2)(5) and Article 2(2)(8) respectively, because the two categories carry different regulatory obligations.

Does the US FDA use the term “IMP”?

Not in its own regulations. 21 CFR Part 312 consistently uses “investigational new drug” and “investigational drug” (defined as synonymous at 21 CFR 312.3). US-based sponsors and CROs running multi-region trials frequently use “IMP” colloquially when coordinating with EU/UK regulatory, manufacturing, or supply-chain partners, and the ICH E6 GCP standard both regions cite uses the neutral term “investigational product” — but “IMP” itself is not FDA’s own defined term.