Short, no-noise briefings on the regulatory changes that affect your company — and what to do about them. Last reviewed: October 2026.
PIC/S PI 006-4: a new reference for qualification and validation
On 1 October 2026 the PIC/S recommendation PI 006-4 came into force, replacing the 2007 PI 006-3 document and aligning it with the Annex 15 revised in 2015. It covers the validation master plan, prequalification and the IQ/OQ/PQ stages, process validation — including ongoing process verification — transport, packaging, supporting utilities and cleaning validation, with risk management as the common thread.
Although it is not binding, it is the working guide for PIC/S inspectors — AEMPS among them — so it is worth checking your master plan and protocols against it. The EU and PIC/S are also preparing a revision of Annex 15 itself, with the draft expected for public consultation in December 2026.
Revised Annex 19: retention samples for parallel imports
In June 2026 the European Commission published the first revision of Annex 19 since 2006, applicable from 24 September 2026. The change centres on a new section 9 for parallel imported, distributed and traded products: reference samples of the re-packaged product are not required, but a retention sample must be kept for each re-packaging operation, for at least one year after expiry, together with the packaging materials used.
Only where duly justified and agreed in advance with the competent authority may the physical sample be replaced by a complete photographic/digital sample, traceable to the batch packaging record. Parallel importers should review their sampling procedures now.
GMP inspections for centrally authorised products: new procedure version
Since 10 September 2026, version 3 of the Union procedure for coordinating the GMP inspections requested by EMA for centrally authorised products applies. The changes are clarifications: where no supporting authority is needed, a single inspectorate will act as both leading and supporting authority.
What has not changed is worth remembering: every site listed in the application must be ready for inspection from the moment it is submitted, and pre-approval inspections are requested by day 90 of the assessment at the latest, under very tight timelines. Keeping the Site Master File and site readiness up to date avoids surprises.
Veterinary medicines: GMP now has its own regulation
Since 16 July 2026, the manufacture of veterinary medicinal products and their active substances is governed by Implementing Regulations (EU) 2025/2091 and 2025/2154, directly applicable without transposition. They turn into law what used to be EudraLex Volume 4 guidance, which no longer applies to these products; the Commission has removed the former Annexes 4 and 5 from it.
The structure will feel familiar, but there are new obligations, above all for the marketing authorisation holder: keeping the specifications and instructions given to the manufacturer aligned with the authorisation, assessing the product quality review when it is not the manufacturer, and putting a written agreement in place with it. The Commission's correspondence tables help locate each requirement.
Reform of EU pharmaceutical legislation: the home stretch
Following the political agreement of December 2025, the Council formally adopted its position at the end of September 2026 and the text is now at second reading in the European Parliament, with the plenary vote indicatively scheduled for November. The new directive and regulation will replace Directive 2001/83/EC and Regulation (EC) 726/2004: 8 years of data protection plus 1 year of market protection (up to 11 in total with incentives), mandatory shortage prevention plans and marketing authorisations valid indefinitely by default.
Once published in the Official Journal, a transition period will run until 2028. The registration, lifecycle and supply decisions taken today will live under that framework — it belongs in your strategic planning now.
Nitrosamines: from one-off crisis to continuous vigilance
The EMA/CMDh framework consolidated the three-step cycle — risk evaluation, confirmatory testing and mitigation — and the CPCA approach for setting limits for API-related nitrosamines (NDSRIs). The key point: it is no longer a closed exercise but a living obligation of the marketing authorisation holder.
Any change of supplier, process or packaging material triggers a re-evaluation, and EMA's Appendix 1 should be followed closely: it is updated regularly with new NDSRIs and revised limits (revision 13 dates from June 2026). Keeping assessments current and traceable is what distinguishes a solid dossier at inspection today.
Clinical Trials Regulation: CTIS is now the only channel
With the transition period over, since 31 January 2025 all clinical trials in the EU are governed by Regulation (EU) 536/2014 and managed through the single CTIS portal: application, coordinated assessment across Member States and publication under the new transparency rules.
For sponsors used to the previous regime, the change affects timelines, documentation and data confidentiality: reviewing internal procedures avoids surprises on the first multinational application.
Annex 1: the Contamination Control Strategy is no longer optional
The revised Annex 1 of the EU GMP requires every sterile manufacturer to maintain a documented, cross-functional and living Contamination Control Strategy (CCS): not a one-off report, but a system connecting facility design, personnel qualification, aseptic process simulations and barrier technologies (RABS, isolators).
AEMPS and EMA inspections now request it systematically, and a merely formal CCS is one of today's most repeated findings. It pays to audit it against real monitoring data, not just against the text of the rule.
ICH Q9(R1): risk management with less subjectivity
The revision of the quality risk management guideline tackles its historical weaknesses: subjectivity in assessments, formality disproportionate to actual risk and decisions poorly grounded in data. It also introduces product availability risk as an explicit concern.
Inspectors now expect more mature QRM systems: fewer decorative colour matrices and more justified decisions. It is a good moment to audit the real quality of the risk exercises in your quality system.
These briefings are informative and do not replace an analysis of your specific situation. If any of them touches your business — or you would like us to assess its impact — write to us and we will reply within 24 working hours.
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