A post-authorisation safety study is one of the few pharmacovigilance activities where a regulator reviews your methodology before you are allowed to begin. Get the protocol right and a PASS can settle a safety question, protect a licence and support future access discussions. Get it wrong and you inherit years of data collection that answers nothing regulators asked.
Voluntary or imposed: the distinction that drives everything
Not every PASS carries the same weight. A study can be initiated voluntarily by the marketing authorisation holder, or it can be imposed by a competent authority under Articles 21a or 22a of Directive 2001/83/EC — typically when the risk-benefit balance of an authorised product depends on evidence that the clinical development programme could not provide.
The classification matters because it determines who assesses your protocol and how binding the outcome is. Non-interventional imposed studies are assessed by the Pharmacovigilance Risk Assessment Committee (PRAC), except where the study is to be conducted in a single Member State at that state’s request, in which case the national competent authority assesses it. Interventional PASS follow clinical trial rules instead. Misclassifying a study at the design stage is one of the more expensive mistakes a safety team can make.
The protocol is the gatekeeper
For imposed non-interventional studies, data collection cannot begin until the protocol has been through regulatory review. The assessing body issues a letter of endorsement or objection within 60 days of submission, and the same 60-day clock applies to substantial protocol amendments, which must be endorsed before they are implemented.
That single fact should shape your project plan. A protocol drafted without regard to EMA’s prescribed format, or one whose objectives drift from the safety concern that triggered the obligation, will attract objections and restart the clock. The elements that draw most scrutiny are:
- Clearly stated objectives tied directly to the identified or potential risk, and to the risk management plan
- A justified data source, with evidence that it can actually capture the exposures and outcomes of interest
- Realistic sample size and precision estimates rather than aspirational ones
- A pre-specified analysis plan, including how confounding and missing data will be handled
- Defined milestones and a plan for interim safety findings that emerge before the study ends
Transparency obligations you cannot retrofit
Since February 2024 the EU PAS Register has been replaced by the HMA-EMA Catalogues of real-world data sources and studies. Imposed non-interventional PASS must be registered there, with the protocol entered before data collection starts, an abstract of the final study report posted within one month of its finalisation, and the final study report submitted to the competent authority within 12 months of the end of data collection.
These are public-facing records. Sponsors who treat registration as an administrative afterthought often discover that what was registered no longer matches what was done — a discrepancy that is trivially visible to any inspector or assessor.
Feasibility before commitment
The most common cause of a failed PASS is not analytical; it is that the chosen data source could never have answered the question. European regulators themselves now run regulator-led real-world data studies through DARWIN EU, drawing on a network of data partners across multiple Member States, and their feasibility-first approach is worth imitating. Before committing to a design, test whether the outcome is coded reliably in the source, whether exposure can be reconstructed, and whether follow-up is long enough for the risk in question. In Greece and other smaller markets, this often means combining sources or joining a multi-country study rather than attempting a national one.
How PQRA helps
PQRA supports marketing authorisation holders across the full PASS lifecycle: classifying the study correctly, assessing data-source feasibility, drafting protocols in the required format, managing PRAC or national competent authority interactions and amendment cycles, handling catalogue registration and reporting deadlines, and integrating study outputs back into the risk management plan and the pharmacovigilance system master file. Our regulatory, pharmacovigilance and market access teams work together, so safety evidence generated post-approval also serves the reimbursement conversations that follow.
If you are facing a new safety obligation, or reviewing a study already under way, contact PQRA to discuss how we can support your programme.
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