Investigational Medicinal Product Dossier (IMPD)

The Investigational Medicinal Product Dossier (IMPD) is the EU and UK clinical-trial-application document that presents the quality (chemistry, manufacturing, and controls), nonclinical, and clinical data supporting the use of a specific medicinal product in a clinical trial. It is a document about the product, submitted to a regulator as part of the application to run a trial — not the product itself. For the product being described, see CASRAI’s Investigational Medicinal Product (IMP) entry; this entry covers the dossier that documents it.

The two terms are often used loosely as if interchangeable, but the distinction matters operationally: a sponsor can have an IMP without yet having assembled a compliant IMPD (a common hold-up in first-in-human trial applications), and the same IMP can be described by different IMPD content depending on the trial’s phase, the product’s authorisation status, and how much nonclinical/clinical experience already exists.

What the IMPD must contain

Under Regulation (EU) No 536/2014, Annex I, Section G, a full IMPD is built around three data sections, each structured to follow the corresponding module of the ICH Common Technical Document (CTD) format:

• Quality data (CTD Module 3 format) — information on the active substance and the finished investigational product: composition, manufacturing process, specifications, analytical methods, container/closure system, and stability data, for the product itself and, where relevant, the comparator or placebo.
• Nonclinical pharmacology and toxicology data (CTD Module 4 format) — summaries of the pharmacology, pharmacokinetics, and toxicology studies (with literature references where applicable) and a critical, safety-focused analysis, generally including a Good Laboratory Practice (GLP) compliance statement for pivotal studies and a discussion of safety margins relative to the exposure planned in the trial.
• Clinical data (CTD Module 5 format) — a summary of any previous clinical trials and other human experience with the product, presented alongside an overall risk-benefit assessment for the proposed trial.

Annex I explicitly encourages cross-referencing the Investigator’s Brochure and clinical trial protocol for the nonclinical/clinical sections rather than duplicating that material inside the IMPD itself — the IMPD’s clinical and nonclinical sections are meant to summarise and critically assess, not restate in full.

Full IMPD vs. simplified IMPD

Annex I, Section G also sets out when a simplified IMPD is acceptable instead of the full three-section dossier above. The main routes are:

• Already-authorised product, used within its marketing authorisation. If the IMP has a marketing authorisation in the EU/EEA (or in an ICH-region country) and is being used in accordance with that authorisation, submitting a current Summary of Product Characteristics (SmPC) can substitute for the full quality/nonclinical/clinical package. Where the product has marketing authorisations with different SmPCs across the Member States concerned by the trial, the sponsor has to justify which SmPC it is relying on.
• Previously-assessed, unmodified product. Where the same IMP, in the same form, was already assessed as part of a previous clinical trial application in the Member State concerned and hasn’t been modified since, the sponsor can refer back to that earlier submission instead of resubmitting the underlying data.
• Placebo. A placebo’s documentation requirement is limited to quality data. If the placebo has the same composition as the tested product (other than the active substance), comes from the same manufacturer, and is not required to be sterile, no further documentation is typically needed at all.

Which route applies is assessed product-by-product and trial-by-trial — a single multi-arm trial can legitimately combine a full IMPD for a first-in-human test article with a simplified, SmPC-referencing IMPD for an authorised comparator arm.

IMPD vs. Investigator’s Brochure

The IMPD and the Investigator’s Brochure (IB) (a document required under ICH GCP) cover overlapping ground — both summarise nonclinical and clinical data on the product — but they serve different audiences and sit in different places in the trial paperwork:

• The IB is written for investigators and site staff: it’s the reference document they use to make clinical judgements during the trial (e.g., assessing whether an adverse event is expected), and it’s the source of the trial’s reference safety information for expedited safety reporting.
• The IMPD is written for the regulator assessing whether the trial should be authorised: its nonclinical and clinical sections are explicitly permitted to cross-reference the IB rather than repeat it, so in practice a compliant IMPD often incorporates the IB by reference for those sections and focuses its own original content on the quality/manufacturing data the IB does not cover.

Where the IMPD fits in the application

In the EU, the IMPD is one of the documents that make up Part I of the clinical trial application dossier under Regulation (EU) No 536/2014, Annex I — alongside the cover letter, application form, protocol, IB, and GMP compliance documentation — submitted through the Clinical Trials Information System (CTIS), the EU’s single mandatory clinical-trial application and authorisation portal. A separate Auxiliary Medicinal Product Dossier covers any auxiliary (non-investigational) medicinal product used in the trial under the protocol; it follows the same quality/nonclinical/clinical logic but for a product that isn’t itself being tested.

The UK left the EU before Regulation 536/2014 became applicable and is not part of CTIS. UK clinical trial applications instead go through the MHRA (assessed alongside Health Research Authority/Research Ethics Committee review via the UK’s combined review service), under the domestic Medicines for Human Use (Clinical Trials) Regulations 2004 (SI 2004/1031, as amended) — but MHRA guidance requires an IMPD covering the same underlying quality, manufacturing, and safety ground, and an active substance master file (ASMF) alone is explicitly not an acceptable substitute for it.

Worked examples

Example 1. A sponsor preparing a first-in-human Phase 1 trial of a novel small-molecule compound submits a full IMPD: complete CTD Module 3 quality data on the drug substance and drug product, a Module 4 nonclinical summary covering the GLP toxicology package that supported the trial’s proposed starting dose and safety margin, and a Module 5 section noting there is no prior human experience with the compound.

Example 2. A Phase 3 trial testing a novel drug against an already-marketed comparator, used strictly within that comparator’s approved indication and dose, submits a full IMPD for the novel drug and a simplified IMPD for the comparator — consisting of the comparator’s current SmPC rather than a full quality/nonclinical/clinical package, since it is authorised and being used on-label.

Counter-example. A sponsor submits an active substance master file (ASMF) from the manufacturer in place of an IMPD for a novel, unauthorised compound, reasoning that the ASMF already documents the substance’s chemistry and manufacturing. This does not satisfy the IMPD requirement — per MHRA guidance, an ASMF is not an acceptable substitute for an IMPD, and the sponsor must still provide the dossier (or a documented justification for withholding a specific element of it).

References

• Regulation (EU) No 536/2014 of the European Parliament and of the Council, Article 2(2) and Annex I (Section G, Investigational Medicinal Product Dossier) — eur-lex.europa.eu, CELEX 32014R0536
• European Commission, “Detailed guidance for the request for authorisation of a clinical trial” (Regulation 536/2014 guidance documents), health.ec.europa.eu
• MHRA / GOV.UK, “Clinical trials for medicines: apply for authorisation in the UK”
• The Medicines for Human Use (Clinical Trials) Regulations 2004 (SI 2004/1031, as amended) — legislation.gov.uk
• ICH E6(R2) Good Clinical Practice, on the Investigator’s Brochure and reference safety information