Pharmacovigilance
Pharmacovigilance is the standing obligation that begins the day a medicine is authorised and ends only when the last obligations of the last market are discharged: to collect, assess, and act on evidence about the product's safety in real use. The EU codifies it in the Good Pharmacovigilance Practices modules — a system architecture with a qualified person for pharmacovigilance (QPPV) personally accountable for it, described in a pharmacovigilance system master file that an inspector can open on any given day. In the US, postmarketing reporting for drugs runs under 21 CFR 314.80. The operational unit is the individual case safety report: received from any source — a clinician, a patient, the literature, a partner — processed, medically assessed, and where criteria are met, submitted to authorities inside fixed clocks, in the ICH E2B(R3) electronic format, with expectedness judged against the reference safety information.
What this page does not claim
Phases are an organising device, not a regulatory mandate — real programmes overlap them, and a medical device, a food product and a small-molecule drug traverse them differently. Each page says where the differences bite.
What happens in this phase
Pharmacovigilance is the standing obligation that begins the day a medicine is authorised and ends only when the last obligations of the last market are discharged: to collect, assess, and act on evidence about the product's safety in real use. The EU codifies it in the Good Pharmacovigilance Practices modules — a system architecture with a qualified person for pharmacovigilance (QPPV) personally accountable for it, described in a pharmacovigilance system master file that an inspector can open on any given day. In the US, postmarketing reporting for drugs runs under 21 CFR 314.80. The operational unit is the individual case safety report: received from any source — a clinician, a patient, the literature, a partner — processed, medically assessed, and where criteria are met, submitted to authorities inside fixed clocks, in the ICH E2B(R3) electronic format, with expectedness judged against the reference safety information.
Above the case level sits the analytical layer. Signal management — detection across case data, literature, and increasingly statistical screening of large safety databases — asks whether the accumulating evidence changes what is known about the product; ICH E2A supplies the foundational definitions the case clocks turn on, and periodic reports in the ICH E2C(R2) tradition present the evolving benefit-risk evaluation to regulators on a schedule. Where risks need active management, risk-management plans and, in the US, risk evaluation and mitigation strategies translate assessment into measures — educational materials, restricted distribution, additional monitoring — whose effectiveness must itself be evaluated. The whole apparatus runs on the safety database: a validated system whose duplicate detection, coding consistency, and submission connectivity are inspection subjects in their own right.
The multi-industry mirror is instructive. Veterinary medicines carry their own pharmacovigilance obligations — in the EU, under Regulation 2019/6, with union-level signal management expectations — and add a human dimension: adverse events in the animal's handler are reportable too. Cosmetics in the US acquired serious-adverse-event reporting duties under MoCRA; devices run a parallel world covered by the next phase. Quality's role in pharmacovigilance is the system's conscience: compliance monitoring of the clocks, audits of the system and its vendors, reconciliation between the safety database and every source that feeds it — clinical databases, medical information, partners under safety-data-exchange agreements — and inspection readiness for a file that is, by design, always open.
- A marketing authorisation in force, with the pharmacovigilance system — QPPV where required, master file, procedures — operational from day one of marketing.
- A validated safety database with E2B(R3) submission connectivity to the relevant authorities.
- Reference safety information established per product, governing expectedness judgements.
- Safety-data-exchange agreements in place with every partner, licensee, and vendor that can receive a case.
- This phase runs for the marketed life of the product; its gates are continuous rather than terminal.
- Expedited cases submitted within regulatory clocks, with compliance monitored and misses investigated.
- Signals detected, validated, assessed, and closed with documented outcomes — label change, risk measure, or refutation.
- Periodic safety reports submitted on schedule with a current benefit-risk evaluation.
- On withdrawal or licence lapse, residual reporting and record obligations identified and discharged into the final phase.
SPEQ synthesis. Phase boundaries and gate criteria are an organising device for planning and review, not a regulatory mandate. Real programmes overlap phases and re-enter them; treat these as the questions worth answering, not a compliance checklist.
- Audit the pharmacovigilance system, its vendors, and its partners against GVP and the master file's description of itself.
- Monitor compliance metrics — case timeliness, submission success, reconciliation completeness — and force investigation of misses.
- Own reconciliation between the safety database and its feeder systems: medical information, product quality complaints, clinical data, partners.
- Maintain inspection readiness for the PSMF and the system it describes, on the assumption of unannounced scrutiny.
- Assure the validated state of the safety database and the change control around its coding dictionaries and submission rules.
- Individual case safety reports with their assessments and submission records
- The pharmacovigilance system master file, current and inspection-ready
- Signal-management records from detection through validated outcome
- Periodic benefit-risk reports (PSUR/PBRER tradition) per schedule
- Risk-management plans and effectiveness evaluations of their measures
- Compliance and reconciliation metrics with their corrective actions
- Late expedited reports from handoff friction — the case arrived, but sat between intake, assessment, and submission while the clock ran.
- Under-reporting hidden in reconciliation gaps: cases visible in medical-information logs or partner systems that never reached the safety database.
- Signal detection performed but not concluded — evaluations open for years, which inspectors read as a system that detects and then declines to decide.
- The PSMF describing an idealised system that interviews and records contradict within the first hour of inspection.
- Safety-data-exchange agreements missing for a licensing partner, discovered when a partner-held case surfaces late by months.
Derived from the 7 standards SPEQ maps to this phase, across 4 regulatory bodies: EMA, FDA, ICH, EC.
FREQUENTLY ASKED
What makes a case "expedited" and what clock applies?
The combination of seriousness, causality, and expectedness, assessed against definitions descending from ICH E2A. A case involving a serious adverse reaction — death, life-threatening, hospitalisation, disability, congenital anomaly, or otherwise medically important — with at least a reasonable possibility of causal relationship generally triggers expedited submission, with the tightest clocks reserved for serious unexpected reactions: those not consistent with the reference safety information. The clocks start at first receipt by anyone in the organisation or its partners — not at the safety department's door — which is why intake routing and day-zero discipline are perennial inspection findings.
What is the QPPV actually accountable for?
The pharmacovigilance system as a whole — personally. The EU requires each marketing-authorisation holder to have a qualified person for pharmacovigilance, permanently and continuously at its disposal, with oversight of the system's functioning: that cases flow, clocks are met, signals are managed, and the system master file honestly describes reality. The QPPV must have the authority to influence the system, not merely observe it — an arrangement where the QPPV learns of problems from the inspector demonstrates the role was decorative. National rules may add local responsible persons alongside the EU role.
Do veterinary and cosmetic products have pharmacovigilance obligations?
Yes — scaled and shaped differently. EU veterinary medicines carry a full pharmacovigilance system under Regulation 2019/6, with adverse events in treated animals and in exposed humans both reportable, and signal management expected at the product level. In the US, MoCRA brought cosmetics their first federal serious-adverse-event reporting duty, with records retention behind it. Food operates through different machinery — reportable-food and consumer-complaint channels rather than case-based pharmacovigilance. The practitioner's transferable insight: every regime turns on the same three gears of collection, assessment, and timely reporting; only the thresholds and clocks change.