Interim Head of Drug Safety: first 90 days

Most small biotechs do not need a permanent Head of Drug Safety from day one. They do need someone who owns safety decisions, and who can show regulators that ownership in writing. The gap usually opens at a predictable moment: a first-in-human trial, an expanding programme, a lost key person, or a marketing authorisation application coming over the horizon. An interim Head of Drug Safety fills that gap with senior medical judgement while the company decides what its long-term pharmacovigilance organisation should look like.

This article sets out the triggers that usually justify an interim appointment, what the role is accountable for under EU, US and ICH requirements, and a practical 90-day plan.

Why accountability matters more than headcount

Outsourcing case processing to a CRO or safety vendor is normal and sensible. Outsourcing accountability is not possible. Under the EU Clinical Trials Regulation the sponsor must report suspected unexpected serious adverse reactions (SUSARs) to EudraVigilance within 7 days if fatal or life-threatening and within 15 days otherwise, and must submit an annual safety report for each investigational medicinal product [1]. In the US, the sponsor of an IND must submit IND safety reports within 15 calendar days of determining that information qualifies, and within 7 calendar days for unexpected fatal or life-threatening suspected adverse reactions [2]. ICH E2F asks for a single Development Safety Update Report (DSUR) per active substance, prepared by the sponsor [3].

Every one of those obligations depends on medical decisions: is this event serious, is it unexpected against the reference safety information, is there a reasonable possibility of causality, and does the aggregate picture change the benefit-risk balance? A vendor can execute the process. Someone on the sponsor side has to own the judgement and sign off.

Typical triggers for an interim appointment

Situation	Why it creates a gap	What the interim lead typically owns
First-in-human or first multinational trial	Safety processes, safety management plan and vendor oversight do not yet exist	Safety governance, reference safety information, SUSAR decision rules
Departure or long absence of the safety lead	Decisions stall; DSUR and signal reviews slip	Continuity of medical review, sign-off and authority interactions
Programme expansion (new indication, combination, paediatric work)	Safety profile assumptions need revisiting	Aggregate review, investigator brochure safety sections, risk assessment
Preparing an MAA or NDA	Post-authorisation obligations must be designed before approval	EU RMP, pharmacovigilance system design, QPPV and PSMF readiness
Emerging safety concern	Rapid, defensible decisions needed under scrutiny	Signal evaluation, authority communication, risk minimisation proposals
Audit or inspection findings	Corrective actions need an accountable owner	CAPA plan, process redesign, training

Interim Head of Drug Safety and EU QPPV are different roles

The two roles are often confused. Once a product holds an EU marketing authorisation, the marketing authorisation holder must have an appropriately qualified person responsible for pharmacovigilance (QPPV) permanently and continuously at its disposal, and the QPPV must reside and operate in the EU (or Norway, Iceland or Liechtenstein under the EEA agreement), with back-up arrangements in place [4][5]. The QPPV is responsible for establishing and maintaining the pharmacovigilance system.

A Head of Drug Safety, interim or permanent, is a functional leadership role: medical review, safety strategy, signal and aggregate assessment, and the safety input to development and regulatory decisions. In a clinical-stage company there is usually no QPPV yet. Before an MAA, the interim lead should plan who will act as QPPV, where the pharmacovigilance system master file (PSMF) will sit, and whether the two roles will be held by one person or two.

The first 90 days

The aim of the first 90 days is not to build a large department. It is to make safety decisions traceable, close compliance exposure and leave the company with a realistic plan.

Days 1–30: understand and stabilise

Map the obligations. List every trial, country, investigational product and authority relationship, with each reporting clock: SUSARs, DSUR data lock point, ethics committee requirements, and any US IND annual report.
Read the contracts. Check safety data exchange agreements and vendor contracts for who does what, timelines, reconciliation and audit rights. Gaps here are among the most common sources of late reports.
Confirm the reference safety information. The investigator brochure RSI drives expectedness and therefore SUSAR reporting. Check which version is in force, when it was last approved and whether it is used consistently by the vendor.
Review open safety issues. Pending medical reviews, unresolved queries, overdue reconciliations and any events of special interest.
Establish decision records. Agree where medical decisions, rationales and sign-offs are documented. If a decision is not written down, an inspector will treat it as not made.

Days 31–60: build governance

Safety governance. Set up a cross-functional safety review group with a charter, membership, meeting frequency and escalation rules, so that safety decisions are made in a defined forum rather than by email.
Safety management plan. Agree with the CRO or vendor how cases are processed, medically reviewed, unblinded where needed and reported, and how the sponsor oversees that work.
Aggregate review. Introduce periodic cumulative review of trial safety data, not only case-by-case assessment. ICH E2F describes the DSUR as a comprehensive, thoughtful annual review and evaluation of pertinent safety information, and that is far easier if review happens throughout the year [3].
Procedures and training. A small set of fit-for-purpose SOPs is better than a large library nobody follows. Train the people who actually perform the steps and keep records.

Days 61–90: look ahead

DSUR readiness. Lock the timetable for the next DSUR, the data sources and responsibilities. The DSUR is due within 60 calendar days of the data lock point [3].
Post-authorisation design. If an MAA is within two years, start the EU RMP safety specification and pharmacovigilance plan, following GVP Module V and ICH E2E [6][7]. Begin designing the pharmacovigilance system that will be described in the PSMF.
Inspection perspective. EU guidance states that, in principle, a marketing authorisation holder should be inspected within four years of the authorisation of its first medicinal product, and that pre-authorisation inspections may be performed [8]. The system you build now is the system that will be inspected.
Long-term organisation. Recommend a target model: what stays in-house, what is outsourced, which roles need hiring and when, and how the transition from interim to permanent leadership should run.

What good handover looks like

An interim engagement succeeds when the company is less dependent on the interim lead at the end than at the start. Practical markers are a documented safety governance structure, current procedures with training records, clear vendor oversight, an up-to-date RSI process, a DSUR plan, and a written recommendation on the future safety organisation. If an MAA is planned, add a pharmacovigilance system roadmap covering QPPV, PSMF, quality system and audit.

Common pitfalls

Treating the vendor as the safety function. Vendors process cases; sponsors decide.
Unclear sign-off. Medical decisions recorded in emails or meeting chats are hard to retrieve and easy to challenge.
Starting RMP and system design too late. Post-authorisation obligations apply from the day of approval and are expensive to retrofit.
Over-engineering. A 15-person company does not need the procedures of a large pharmaceutical group. It needs proportionate, followed and documented processes.

If your company is approaching one of these triggers, an interim Head of Drug Safety can provide senior medical safety leadership while you decide on the permanent set-up. Contact us to discuss your situation.

Sources

This article is for information only and is not medical or regulatory advice.

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