This guideline provides international standards and definitions for managing and reporting safety information for medicines after they have been approved and are on the market (the “post-approval” or “post-marketing” phase). Its goal is to ensure that safety data is collected, evaluated, and reported consistently and with high quality across different regions.
Key Dates:
- Final Adoption: 18 September 2025
- Effective Date: 18 March 2026 (From this date, companies must comply).
Summary of Key Sections
1. Introduction
This section sets the stage, explaining that the guideline harmonizes how companies handle safety reports after a drug is approved. It connects to other ICH guidelines:
- ICH E2A: Covers clinical trial safety data.
- ICH E2B: Defines the electronic format for submitting individual case safety reports (ICSRs).
- ICH E2C: Covers periodic safety update reports (PSURs).
It also emphasizes that while it aims for global harmony, companies must always check and follow specific regional and local regulations, which may differ.
2. Definitions and Terminology
This is a critical section that defines the core concepts of pharmacovigilance.
- Adverse Event (AE): Any bad medical occurrence in a patient who took a medicine. It doesn’t have to be caused by the medicine.
- Adverse Drug Reaction (ADR): A harmful and unintended response to a medicine where a causal relationship is at least a reasonable possibility. Crucially, for reporting, any event spontaneously reported is treated as an ADR.
- Serious AE/ADR: Defined by specific outcomes like death, life-threatening, requires hospitalization, causes disability, birth defects, or other “important medical events.”
- Unexpected AE/ADR: An event not listed in the local product label (e.g., SmPC, Prescribing Information), or whose nature, severity, or specificity is not consistent with the label.
- Individual Case Safety Report (ICSR): The formal report for a single patient. To be valid, it must have four minimum criteria:
- An identifiable patient.
- An identifiable reporter (the primary source of information).
- At least one suspect medicinal product.
- At least one adverse event (or “other observation”).
- Expedited Report: An ICSR that must be reported to regulators as soon as possible, but no later than 15 calendar days from “Day 0.”
- Organised Data Collection System (ODCS): A key concept. Any planned activity to gather data on a product or disease, making it reviewable. This includes clinical trials, non-interventional studies, Patient Support Programs (PSPs), Market Research Programs (MRPs), and even digital “social listening.” Standard spontaneous reporting is excluded from this definition.
3. Types of Individual Case Safety Reports
- Spontaneous Reports: Unsolicited communications from a Healthcare Professional (HCP) or consumer about a suspected AE/ADR. These are not collected as part of a formal study or program (ODCS).
- Solicited Reports: Reports derived from an ODCS (e.g., from a clinical trial, PSP, or MRP). These must be classified as “report from study” in the E2B format and require a causality assessment.
4. Sources of Individual Case Safety Reports
This section details where companies can find safety information and how to handle each source.
- HCPs & Consumers: Direct communications (can be spontaneous or solicited).
- Literature: Companies must screen published scientific literature. An ICSR is needed if the article’s author suspects a causal link. The “primary source” is the first author.
- Digital Platforms:
- Under MAH responsibility (e.g., company-owned website/forum): Must be regularly screened. Reports are spontaneous if voluntarily posted, or solicited if found via a planned ODCS activity.
- Not under MAH responsibility (e.g., public social media): No routine screening required. If a company actively searches these platforms as part of an ODCS (e.g., social listening), any AEs found are considered solicited. If an employee accidentally finds an AE outside an ODCS, it’s managed as a spontaneous report.
- Non-Interventional Studies:
- With primary data collection (e.g., new surveys): AEs are solicited reports and should be reported as ICSRs.
- With secondary use of data (e.g., analyzing existing databases): AEs are generally not reported as ICSRs, but are summarized in the final study report.
- Patient Support Programs (PSPs) & Market Research Programs (MRPs): AEs from these ODCS activities are considered solicited reports and must be recorded and assessed for reporting.
- Regulatory Authorities: Cases from a regulator’s database must be reported to other regulators (where required). Companies should not re-report the same case to the original regulator unless they have new information.
5. Standards for Reporting
- What to Report?
- AEs/ADRs: The main focus. Serious + Unexpected cases always require expedited (15-day) reporting. Requirements for other combinations (serious+expected, non-serious) vary by region.
- Important Safety Findings: Significant new risks from studies (e.g., carcinogenicity) must be communicated to regulators immediately, even if not an ICSR.
- Other Observations: Includes pregnancy exposure, lack of efficacy, overdose, medication errors, etc. These are only reported as ICSRs if required by local regulations, especially if no AE/ADR occurred.
- Reporting Timeframes:
- Day 0: The clock starts when the MAH (or its agent) first has enough information to conclude that the four minimum criteria for a reportable ICSR are met.
- Expedited Reports: ≤ 15 calendar days from Day 0.
- Follow-up information on a case resets the clock (new Day 0).
6. Good Case Management Practices
Practical advice for handling cases effectively and accurately.
- Identifiability: Confirming a real patient and reporter exists is crucial to avoid duplicates and ensure authenticity. Basic info like age, sex, or initials is enough for the patient. For a reporter, a name, qualification, or address is sufficient.
- Narratives: The report should tell a clear, stand-alone “medical story” of the case in chronological order.
- Clinical Evaluation: Cases must be medically reviewed to assess seriousness, possible alternative causes, and the need for more information.
- Follow-up: Companies should actively seek more information, especially for serious and unexpected cases. All follow-up attempts must be documented.
- Contractual Agreements: Agreements with partners (e.g., CROs, distributors) must clearly define safety data exchange processes and timelines. The MAH is ultimately responsible for timely reporting.
- Duplicate Management: Systems must be in place to identify and manage duplicate reports to avoid skewing safety data.
- How to Report: ICSRs must be submitted electronically in the ICH E2B format, using MedDRA for coding medical terms.
Conclusion
The ICH E2D(R1) guideline is the foundational standard for post-approval pharmacovigilance. It provides clear definitions for safety data, classifies the types and sources of reports, and sets the standards for timely and high-quality case management and reporting. The revised version (R1) places significant emphasis on modern data sources like digital platforms and structured activities like ODCS, ensuring that safety monitoring practices evolve with technology and data collection methods. Compliance with this guideline is essential for Marketing Authorization Holders (MAHs) to ensure patient safety and meet regulatory obligations globally.
