The short version
What teams need to understand
- All safety information must be captured through defined intake processes.
- Minimum case criteria must be confirmed before a case is processed.
- Day zero must be determined consistently based on when valid information is received.
- All sources of safety information must be identified and documented.
- Case intake processes must ensure traceability from source through intake documentation to safety database entry.
- Inspection-ready evidence should demonstrate complete and controlled case intake procedures.
Regulatory expectation
What regulators expect
Each expectation should be supported by controlled documentation, traceable records, clear ownership, and evidence that the process works in practice.
- All safety information must be captured through controlled processes.
- Minimum case criteria must be verified before case creation.
- Day zero must be consistently determined.
- Case sources must be clearly documented.
- Traceability from source through intake documentation to database entry must be maintained.
Why it matters
What this means in practice
Inspectors assess whether pharmacovigilance systems capture, validate, and document safety information at intake. They typically review how cases are received, how minimum criteria are confirmed, how day zero is determined, and how source information is traceable from original receipt through to database entry.
Questions this page answers
Inspection evidence
Evidence teams should be able to show
ICSR Intake Form
- Structured capture of patient, reporter, product, and event information
- Documentation of source (e.g. HCP, patient, literature, partner)
- Initial seriousness and causality indicators
- Date of receipt and validation of minimum criteria
Case Source Documentation
- Original source documents such as emails, call logs, or literature articles
- Identification of source type (spontaneous, literature, clinical trial, partner)
- Documentation linking source to intake record
- Traceability between source document and safety database entry
Minimum Case Criteria Assessment
- Evidence of identifiable patient
- Evidence of identifiable reporter
- Suspect medicinal product
- Adverse event description
- Documentation confirming case validity
Day Zero Determination Records
- Date of first awareness of a valid case
- Documentation supporting day zero decision
- Consistency between intake record and database entry
- Traceability to reporting timelines
Intake Process SOP
- Defined intake workflow
- Roles and responsibilities for case receipt
- Instructions for validating minimum case criteria
- Procedures for documenting case sources
Regulatory Basis (Primary Sources)
- GVP Module VI - requirements for collection and management of ICSRs
- ICH E2D - post-approval safety data management
- ICH E2A - minimum case criteria requirements
- MHRA GPvP guidance - safety reporting obligations
- FDA 21 CFR 314.80 - postmarketing reporting requirements
Typical Inspection Questions (What Inspectors Ask)
- How do you capture incoming safety information?
- How do you determine whether a case is valid?
- How do you define and document day zero?
- Show me the original source and how it appears in your database.
- What sources generate ICSRs in your system?
Common failure patterns
What good looks like
- Structured intake forms capturing all required information.
- Consistent validation of minimum case criteria.
- Clear and documented determination of day zero.
- Full traceability from source document to intake record to database entry.
- Defined intake processes followed consistently.
How teams operationalise it
- Implement structured intake forms for all safety information.
- Define minimum case criteria and validation steps.
- Ensure all sources of safety information are documented.
- Standardise day zero determination rules.
- Ensure traceability from source through intake documentation to safety database.
- Train staff on intake procedures and requirements.
From expectation to working control
Find the documentation that supports this work
Review the related toolkit to understand its purpose, included files, and how it supports this regulatory expectation.
Frequently asked questions
What is day zero in pharmacovigilance?
Day zero is the date when a company first becomes aware of a valid ICSR containing the minimum required information.
What are the four minimum criteria for an ICSR?
The four minimum criteria are an identifiable patient, identifiable reporter, suspect medicinal product, and an adverse event. A case becomes valid for reporting once all four elements are present.
What sources generate ICSRs?
Sources include spontaneous reports, literature, clinical trials, patient support programmes, and partner organisations.
Do inspectors review intake processes?
Yes. Inspectors frequently review intake forms, source documentation, and day zero determination.
Why is case intake important?
Case intake ensures that all safety information is captured, validated, and processed correctly within regulatory timelines.
What are common intake failures?
Common failures include missing minimum criteria, incorrect day zero, incomplete source documentation, and lack of traceability.
Source boundary
Regulatory sources
These primary sources inform this structured interpretation. Always confirm current requirements against the original source and the requirements applicable to your organisation, product, and jurisdiction.
European Medicines Agency (EMA)
Guideline on good pharmacovigilance practices (GVP) - Module VI
View source
FDA
Postmarketing Safety Reporting
View source
ICH
Clinical Safety Data Management (E2A)
View sourcePost-Approval Safety Data Management (E2D)
View source
MHRA
Good Pharmacovigilance Practice (GPvP)
View source