ICHRegulatory IntelligenceGuideline
ICH E2E

Pharmacovigilance Planning

The ICH guideline on planning pharmacovigilance activities for the early post-marketing period of a new medicinal product (Step 4, 18 November 2004). E2E defines the safety specification — a summary of the important identified risks, important potential risks, and important missing information — and a structure for the pharmacovigilance plan built on it, plus principles of good practice for the design and conduct of observational studies.

LAST REVISED
November 2004
PRODUCT AREAS
Pharmacovigilance

What this does not cover

stated in the document's own scope
  • Covers the planning of pharmacovigilance activities; the management and expedited reporting of individual cases is the province of E2A and E2D(R1).
  • Defines the safety specification and pharmacovigilance plan; the binding EU risk management plan format is set by Regulation (EU) No 520/2012 and GVP Module V.
  • Addresses safety planning; risk minimisation measures and their effectiveness evaluation are elaborated in regional guidance rather than in E2E itself.
SOURCE & PROVENANCE
ISSUING BODY
International Council for Harmonisation
JURISDICTION
International
DOCUMENT ID
ICH E2E
Official site — International Council for Harmonisation

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Overview

ICH E2E is the harmonised guideline on pharmacovigilance planning — how to plan safety activities for a new medicinal product before and during its early post-marketing period. Its central instrument is the safety specification: a structured summary of the important identified risks, the important potential risks, and the important missing information for a product at approval. On that foundation the guideline defines the pharmacovigilance plan: routine pharmacovigilance where the safety profile warrants nothing more, and additional activities — including observational studies — where specific risks or knowledge gaps need active follow-up. An annex describes the pharmacovigilance methods available for those activities, with principles of good practice for designing and conducting observational studies.

Scope & applicability

Pharmacovigilance planning for new medicinal products approaching or entering the market in ICH regions. The safety specification and pharmacovigilance plan it defines became the conceptual basis of the EU risk management plan under GVP Module V.

Legal basis & how it acquires force

An ICH harmonised tripartite guideline, adopted at Step 4 of the ICH process on 18 November 2004, committing the ICH regions to implementation under Step 5. The FDA issued it as guidance for industry in April 2005; the EMA implements it as an ICH scientific guideline, and its concepts were subsequently embedded in the EU pharmacovigilance legislation through the risk management plan required of marketing authorisation applicants.

Document structure

PartCovers
IntroductionObjectives, background, and the products and situations the guideline addresses
Safety specificationThe elements summarising important identified risks, important potential risks, and important missing information
Pharmacovigilance planThe structure of the plan, routine pharmacovigilance, and action plans for specific safety concerns
Annex — pharmacovigilance methodsObservational and other methods available for post-approval safety activities, with good-practice principles for study design and conduct

Key requirements

  • Prepare a safety specification summarising important identified risks, important potential risks, and important missing information
  • Build a pharmacovigilance plan proportionate to the safety specification — routine pharmacovigilance where sufficient, additional activities where not
  • Design observational studies within the plan according to good practice principles

Implementation tips

  • Keep the safety specification a living document — the EU RMP and the PSUR/PBRER family all draw on the same risk inventory, so one maintained source prevents divergence

Revision notes

Adopted at Step 4 on 18 November 2004 and unrevised since; the EU risk management plan (GVP Module V) and the PBRER (E2C(R2)) build on its safety-specification concept.

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International alignment

E2E supplied the conceptual skeleton that later regional instruments formalised: the EU risk management plan under GVP Module V is a direct descendant of its safety specification and pharmacovigilance plan, and the periodic benefit-risk evaluation report of ICH E2C(R2) draws on the same structured risk inventory. Within the ICH E2 family it is the planning guideline, sitting alongside E2A (clinical safety definitions), E2D(R1) (post-approval case management), and E2B(R3) (electronic transmission).

Where to next

Good Pharmacovigilance PracticeWhat GVP covers, and the standards that govern it.

ICH E2E: frequently asked questions

Quick answers to common questions about ICH E2E.

What is the safety specification in ICH E2E?

A structured summary, prepared at approval, of a product's important identified risks, important potential risks, and important missing information — the knowledge gaps that matter, such as populations not studied. It is the foundation on which the pharmacovigilance plan is built.

How does ICH E2E relate to the EU risk management plan?

The EU RMP grew out of E2E: GVP Module V structures the RMP around the same safety specification and pharmacovigilance plan the guideline defines, and adds the EU-specific risk-minimisation part. A team drafting an RMP is working with E2E concepts in a legally required format.

When was ICH E2E adopted?

The guideline reached Step 4 of the ICH process on 18 November 2004, and the regions implemented it in 2005 — the FDA published its version as guidance for industry in April 2005.

Does ICH E2E require additional pharmacovigilance activities for every product?

No. Where the safety specification raises no concern needing active follow-up, routine pharmacovigilance is sufficient. Additional activities — such as observational studies — are proposed only for specific risks or missing information that routine surveillance cannot adequately address.