Description
The Food and Drug Administration (FDA or Agency) is announcing the availability of a draft guidance for industry entitled “E2D(R1) Post-Approval Safety Data: Definitions and Standards for Management and Reporting of Individual Case Safety Reports.” The draft guidance was prepared under the auspices of the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH). The draft guidance updates the existing E2D guidance entitled “E2D Post-Approval Safety Data Management: Definitions and Standards for Expedited Reporting,” published in 2003. The draft guidance is intended is to clarify the use of new or increasingly used data sources ( e.g., social media, market research programs, patient support programs) and update terminology and standards for postmarket adverse event reporting.
Key Topics
Terms and concepts identified from this document
Scope & Applicability
Product Classes
2Class of medicinal products where lack of efficacy may require ICSR reporting
Class of medicinal products where lack of efficacy may require ICSR reporting
Stakeholders
7Provides medical confirmation of reactions or events; Identifiable reporter in a safety report; Source of medical record numbers; Role responsible for medical confirmation of events; Person entrusted with the direct or indirect provision of healthcare services
MAHs are expected to follow-up all pregnancy reports from consumers
Healthcare professionals who reference labeling and public resources
inform patients and HCPs about the benefits and safety of biosimilars
layman using the drug safely
Marketing Authorization Holder responsible for safety reporting; Marketing Authorization Holder responsible for providing exposure data; Marketing Authorization Holder responsible for signal evaluation and reporting.; Marketing Authorization Holder responsible for presenting efficacy information
Entities responsible for referring to local or regional regulatory authority requirements.
Regulatory Context
Regulatory Activities
6Case fulfillment of local criteria for expedited reporting; Does This Case Fulfil the Local Criteria for an Expedited Report?; C.1.7 indicates whether the case fulfils the local expedited requirements.; Regulatory submission type for serious adverse events
clearly assigning responsibility for literature monitoring
Submission of Individual Case Safety Reports to regulatory authorities
Required for cases of AEs/ADRs that are both serious and unexpected
Direct communication by an HCP or consumer describing AEs/ADRs
Reports derived from ODCSs where information is actively sought
Document Types
9Electronic message format for adverse event reporting; Complete information provided by a reporter to describe an event or incident
In countries where ICH E2B is not implemented, CIOMS I may be used
use of a targeted questionnaire/specific form is encouraged to facilitate capture of complete information
Comprehensive stand-alone medical story summarizing clinical information
Electronic transmission of safety data; Data Elements and Message Specification for electronic transmission; Report of information describing adverse events experienced by an individual patient; Electronic messages for transmitting adverse event data; Electronic transmission of safety data elements and message specifications; minimum set of information is always required for an ICSR to be valid; The IG describes data elements for outbound ICH ICSR XML messages.; This data element identifies the
The primary section of drug labeling where SLCs are implemented
Basic product information brochure
Defines the standard of veterinary practice and limits for anesthetic regimens
Individual Case Safety Report
Attributes
6Observation requiring reporting in safety data
Verification of the existence of a patient and a reporter
Criteria for reports that must be submitted within 15 calendar days
Criteria including death, life-threatening, hospitalization, disability, or congenital anomaly.; For serious AEs/ADRs, it is important to continue follow-up
An AE/ADR not included in local/regional product labeling.
The start of the regulatory time clock for reporting ICSRs; The regulatory time clock for reporting starts when the MAH identifies an AE/ADR
Technical Details
Substances
2The substance administered to a patient that may result in an AE or ADR.
Chemical component identified in literature articles; When an active substance has a long half-life, this should be taken into account
Testing Methods
1Regular monitoring of worldwide scientific literature for safety information
Processes
5Other Data Collection Systems including clinical trials and non-interventional studies
Medical review to ensure correct interpretation of medical information
Programs initiated by an MAH where patients enroll to support medicinal product use
Planned collections of healthcare professional or consumer insights for marketing
Process to establish whether an AE/ADR has previously been reported
Clinical Concepts
4Reactions or events observed in patients; Information described in an ICSR; Information associated with the use of biopharmaceuticals; Clinical information corrected during an amendment; Section D describes the singular subject who experienced one or several adverse events/reactions.; Reactions or events observed in patients or foetuses; The onset of a reaction/event following drug administration.; Reporting of reactions to suspect drugs; Reaction or event reported by the primary source; Reactio
Adverse Events and Adverse Drug Reactions identified from various sources; Adverse Events and Adverse Drug Reactions subject to reporting
Basic term defined in section 2.1.2; Noxious and unintended responses to a medicinal product where a causal relationship is a reasonable possibility.
Adverse Events and Adverse Drug Reactions identified during surveillance; For serious AEs/ADRs, it is important to continue follow-up
Identified Hazards
Hazards
9Safety finding requiring reporting; Reports of occupational exposure should be followed up
Reports of misuse should be followed up
Intentional, nontherapeutic use of a drug for psychological or physiological effects.
Safety concern that may require ICSR reporting if associated with AE/ADR; Reports of medication error should be followed up
A risk for which the Agency may require certain packaging or disposal systems.
risk assessment for pharmaceuticals affecting the immune system
Significant unanticipated safety finding suggesting human risk
Hydrogen peroxide is mutagenic and genotoxic in vitro
Reports occurring independently of an AE/ADR that may require ICSR reporting
Standards & References
External Standards
2Used for coding indications, reactions, and causes of death; Coding for indications and sender's diagnosis; Medical Dictionary for Regulatory Activities used for coding medical sections; Medical Dictionary for Regulatory Activities used to classify adverse event information; terminologies include MedDRA for medical history, indication, and reaction; Used for coding medical history, indications, reactions, and causes of death.; Standard terminology used for coding medical history, indications, an
Style specified for literature citations in ICSRs
ICH References (6)
Post-Approval Safety Data: Definitions and Standards for Management and Reporting of Individual Case Safety Reports
MedDRA is also known as ICH M1
Provides guidance on identifiable patients and reporters; Provides definitions for seriousness criteria
Provides definitions for seriousness criteria; ICH E2A recommends blinded therapy should not be reported
Data standard for electronic transmission of individual case safety reports
Covers periodic reporting of aggregated safety data and Company Core Safety Information.; Guidelines for periodic reports where observations in the absence of an AE/ADR should be discussed
Related MFDS Guidelines
Korean regulatory guidelines covering similar topics
See Also (8)
- E11A Pediatric Extrapolation
- M15 General Principles for Model-Informed Drug Development
- Clinical Pharmacology Data to Support a Demonstration of Biosimilarity to a Reference Product
- Q6A Specifications: Test Procedures and Acceptance Criteria for New Drug Substances and New Drug Products: Chemical Substances
- Rare Diseases: Considerations for the Development of Drugs and Biological Products
- Q3C Impurities: Residual Solvents_2011
- Providing Regulatory Submissions in Electronic Format --Content of the Risk Evaluation and Mitigation Strategies Document Using Structured Product Labeling: Guidance for Industry
- Q4B Annex 5: Disintegration Test General Chapter