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. Supply planning also has to account for commercial-market disruption: the FDA drug shortage list is the primary U.S. source for confirming whether a marketed product used in a trial is currently in shortage.

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 (see comparator sourcing) — 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.

IMP vs. NIMP (auxiliary medicinal product): why the classification matters

A trial protocol routinely involves more than one medicinal product, and only some of them are IMPs. The dividing line under Regulation (EU) No 536/2014 is not what a product is chemically, but the role it plays in the protocol: a product being tested, or used as the reference/comparator/placebo against which the test article is measured, is drawn directly into the IMP definition at Article 2(2)(5). A product the protocol requires for a different reason — to manage the trial safely, treat an adverse event, or provoke a measurable response the test article is then assessed against — typically falls instead under the auxiliary medicinal product (AxMP) category at Article 2(2)(8), the current term for what was called a “non-investigational medicinal product” (NIMP) under the older EU Clinical Trials Directive 2001/20/EC. “NIMP” is still the term most researchers search for and still appears in older EudraLex Volume 10 guidance and in day-to-day trial-team usage, even though Regulation 536/2014 itself uses “auxiliary medicinal product.”

Common examples of products that typically fall on the AxMP/NIMP side of the line, as distinct from an IMP:

• Rescue medication — a product administered per protocol to manage a specific adverse event or symptom (e.g. a corticosteroid for an infusion reaction), not itself being tested or used as a comparator.
• Background or run-in medication — standard-of-care treatment participants continue on throughout the trial, required by the protocol but not the object of the investigation.
• Challenge agents — a substance administered specifically to provoke a physiological, allergic, or immune response (for example in a controlled human infection or bronchial challenge study) so that the test article’s effect on that response can be measured; the challenge agent itself is usually not what is under investigation, though its classification depends on the specific protocol and needs to be assessed case by case.
• Diagnostic agents used to assess eligibility, response, or safety during the trial, where the diagnostic product itself is not being investigated.

An active comparator, by contrast, usually stays on the IMP side of the line precisely because Article 2(2)(5) explicitly extends the IMP definition to a product “used as a reference” — the comparator is central to what the trial is measuring, not incidental to running it.

The classification is not a paperwork technicality: it determines which set of obligations attach to the product. IMPs and AxMPs are subject to different Investigational Medicinal Product Dossier (IMPD) documentation expectations, different Annex VI labelling particulars, and different Qualified Person (QP) certification and batch-release requirements (see below) — an authorised AxMP used strictly within its marketing authorisation can often move through a lighter-touch pathway than an unauthorised IMP, while getting the classification wrong risks releasing or labelling a product incorrectly for its actual regulatory category.

Labelling under Annex VI

Regulation (EU) No 536/2014’s Annex VI (“Labelling of Investigational Medicinal Products and Auxiliary Medicinal Products”) sets the harmonised EU/UK-derived labelling particulars for IMP and AxMP packaging, replacing the older Annex 13 to the EU GMP framework used under Directive 2001/20/EC. Annex VI distinguishes two labelling regimes:

• Unauthorised IMPs/AxMPs (products with no marketing authorisation in the country of use, or used outside their authorised terms) require the fuller set of particulars — including a subject identification number and/or treatment number, visit number where relevant, and the period of use (expiry or re-test date) — alongside sponsor/CRO and trial-identifying information, since the product cannot rely on an existing approved label to communicate that information.
• Authorised products used as IMPs/AxMPs strictly within their existing marketing authorisation (same indication, form, and dose) qualify for simplified labelling, since patients and site staff can rely on the product’s existing approved label for most safety information.

Annex VI also sets rules for where particulars must appear when a product ships with both immediate (e.g. blister, ampoule) and outer packaging: where the two are intended to stay together, or where the immediate packaging is too small to carry full labelling, the outer packaging must carry the full particulars while the immediate packaging can omit the period-of-use (expiry/re-test) date. A 2022 delegated act (effective 15 November 2022) confirmed this simplified approach specifically to reduce the safety and quality risk of repeatedly re-labelling small immediate containers, such as re-opening tamper-evident seals to update an expiry date. This is a materially different labelling regime from a standard marketed-drug label, and from the US IND framework, which does not have a directly equivalent harmonised annex — 21 CFR 312.6 sets its own, shorter set of investigational-label requirements, including the statement “Caution: New Drug–Limited by Federal law to investigational use.”

QP certification, batch release, and supply-chain accountability

Before an IMP batch can be released to a clinical trial site in the EU/UK, a Qualified Person (QP) named on the manufacturing or importation authorisation must certify that the batch was manufactured and tested in accordance with EU GMP and the specifications in the Clinical Trial Application/IMPD — the EU GMP framework’s equivalent of a marketed-product QP release, applied to trial material. This obligation applies both to IMPs manufactured within the EU/UK and to IMPs manufactured in a third country and imported for use in an EU/UK trial, where the importing site’s QP must certify the batch before it can be distributed to sites. Because AxMPs used strictly within an existing marketing authorisation can rely on that authorisation’s own quality assurance, QP certification burden concentrates most heavily on IMPs and on AxMPs used outside their authorised terms.

QP release is the regulatory gate; day-to-day supply-chain accountability is the operational discipline that keeps it defensible. Site-level drug accountability logs — tracking receipt, dispensing to each subject, patient returns, and eventual destruction or return to the sponsor/depot — have to reconcile against the QP-released batch quantity, and IMPs with narrow storage tolerances (many are temperature- or light-sensitive) need documented cold-chain handling from release through dispensing. This entry deliberately keeps that operational detail brief: CASRAI’s Clinical Trial Supply Management guide covers GMP manufacturing, packaging/blinding, cold-chain logistics, and full site-level accountability mechanics for both IMPs and AxMPs across the trial lifecycle.

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.

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.

What is the difference between an IMP and a NIMP (auxiliary medicinal product)?

An IMP is the product under investigation, or used as its reference, comparator, or placebo (Regulation (EU) No 536/2014, Article 2(2)(5)). A NIMP — now formally called an auxiliary medicinal product (AxMP) under Article 2(2)(8) — is a different medicinal product the protocol requires for another reason, such as rescue medication, background therapy, or a challenge agent, that is not itself being tested or used as the trial’s comparator. The classification determines which Annex VI labelling particulars and QP release requirements apply.

What are the labelling requirements for an IMP under Annex VI?

Annex VI to Regulation (EU) No 536/2014 sets harmonised labelling particulars for unauthorised IMPs and AxMPs (including subject/treatment number, visit number, and period of use), with a simplified labelling regime available for authorised products used strictly within their existing marketing authorisation. It also sets rules for what must appear on immediate versus outer packaging, including a 2022 simplification for expiry dates on small immediate containers.

Who releases an IMP for use at a clinical trial site?

A Qualified Person (QP) named on the relevant manufacturing or importation authorisation must certify each IMP batch against EU GMP and the Clinical Trial Application/IMPD specifications before it can be released to a trial site — required both for IMPs manufactured in the EU/UK and for IMPs imported from a third country. See CASRAI’s Clinical Trial Supply Management guide for the full release and distribution workflow.