EU GMP Annex 19 Revised: Reference and Retention Samples From 24 September 2026

For twenty years, the way European manufacturers and importers store reference and retention samples followed a single document that never changed. That document is Annex 19 of the EU Guidelines for Good Manufacturing Practice, and its 2006 version had governed sampling practice since 1 June 2006. On 24 June 2026 the European Commission published a revised Annex 19 by decision C(2026) 4135 final. It becomes applicable on 24 September 2026, three months after publication. For any company that imports, re-packages, parallel distributes or certifies medicinal product batches for the European market, the countdown has already started.

This is the first change to Annex 19 in two decades, and it is not a cosmetic refresh. It adds an entirely new Section 9 that sets out, for the first time, how reference and retention samples must be handled for parallel imported, parallel distributed and parallel traded products. It also introduces a controlled route to keep photographic or digital samples in place of physical ones. If your sampling standard operating procedures and written agreements were drafted against the 2006 text, they are now out of date. This guide explains what changed, what stayed the same, and the practical steps to take before the deadline.

Executive summary: the Annex 19 revision at a glance

Here is the revision in brief for quality and regulatory leaders who need the decision, not the detail.

• What changed: The European Commission published a revised Annex 19 by decision C(2026) 4135 final on 24 June 2026.
• Headline impact: A new Section 9 governs reference and retention samples for parallel imported, distributed and traded products, and a new route allows photographic or digital retention samples under strict conditions.
• Why it happened: The GMP and GDP Inspectors Working Group and the PIC/S Committee jointly recommended the revision, focused on parallel trade.
• Legal basis: Article 47 of Directive 2001/83/EC, interpreting the GMP principles in Commission Directive 2017/1572/EU.
• Timeline: Applicable 24 September 2026, three months after publication. There is no separate transition beyond those three months.
• What to do: Revise sampling SOPs, written agreements under Chapter 7, and Qualified Person access arrangements now, and build an Annex 11 compliant process before relying on any digital sample.

What is Annex 19?

Annex 19 is the part of EudraLex Volume 4, the EU GMP guide, that governs the taking and holding of reference and retention samples. It applies to medicinal products for both human and veterinary use. A reference sample is kept so a batch can be analysed if a question arises during its shelf life. A retention sample is a fully packaged unit kept for identification, so that presentation, packaging, labelling and the patient information leaflet can be checked later.

The distinction matters because the two sample types answer different questions. The reference sample answers whether the product still meets its specification, so it must be large enough to run the full analytical controls on at least two occasions. The retention sample answers whether this is what was released to the market, so it must be a complete, fully packaged unit. For many finished products the reference and retention sample are presented identically as fully packaged units, and in that case they may be treated as interchangeable.

What the 2026 revision changes

The substance of the revision is concentrated in a new Section 9 on parallel trade, plus a new digital sampling option. The general rules on duration, size, storage and written agreements are carried over from the 2006 version with little change. The table below summarises the practical shifts.

The retention rules that did not change

It is just as important to know what stayed the same, because these are the rules inspectors will still expect you to meet. The revision did not touch the core durations, sample sizes, storage locations or the Qualified Person duties.

For products manufactured outside the EEA, the position also holds. Where an operational Mutual Recognition Agreement is in place, reference samples may be stored at the site of manufacture under a written agreement, but retention samples must still be kept within the EEA. Where no such agreement applies, reference samples of the finished product must be taken and stored at an authorised manufacturer inside the EEA.

Section 9: the new rules for parallel trade

Section 9 is the heart of the revision. It applies to parallel imported, parallel distributed and parallel traded products, which are medicines re-packaged or re-labelled for a different national market. Until now, Annex 19 was silent on how these operators should sample. The new section sets clear, and in places relieving, expectations.

You do not need a reference sample of the re-packaged product

Section 9.2 states plainly that reference samples of the re-packaged product are not required. This is a sensible relief, because the parallel operator does not change the medicinal product itself, only its outer presentation for the destination market. The analytical reference sample obligation sits with the original manufacturer, not the re-packager.

You do need a retention sample for every re-packaging operation

Section 9.3 requires a retention sample of the re-packaged finished product for each re-packaging operation, retained for at least one year after the expiry date. Section 9.4 adds that this sample must represent the product released to the market and must include both the primary and the secondary package. Where the secondary package is not opened, only the packaging material used needs to be retained. In practice this means a parallel distributor cannot batch several re-packaging runs under one sample. Each operation stands on its own.

You must keep the re-packaging materials too

Section 9.1 requires physical samples of the packaging materials used in re-packaging, such as labels, the carton, the patient information leaflet and any other inserts, to be retained for the shelf life of the re-packaged product. For high volume parallel operations, this is a document and storage control question as much as a sampling one, because the materials must be traceable to the specific re-packaging batch record.

Photographic and digital retention samples

For the first time, Annex 19 allows a photographic or digital sample to replace a physical retention sample. This is the change that has drawn the most attention, and it is also the one most likely to be misread. It is not a free choice. Section 9.5 permits it only where it is duly justified that a physical retention sample cannot reasonably be kept, and only where this has been agreed in advance with the competent authority.

When it is allowed, the digital sample carries strict content and integrity conditions. It must be a complete record that allows full visual examination and investigation equivalent to a physical sample. Under sections 9.5.1 to 9.5.3, it must include high quality photographs, all data on both the primary and secondary packaging such as batch number and expiry date, evidence that the safety features have been applied, and it must allow identification of information in braille. Under section 9.5.4, any digital sample stored electronically must comply with the principles of Annex 11 to ensure the integrity of the record over the whole retention period.

Who is affected by the Annex 19 revision

• Parallel importers, distributors and traders re-packaging or re-labelling medicines for EU markets, who now have explicit sampling duties under Section 9.
• EU importers and sites of batch release, who must confirm reference and retention sample arrangements meet the revised text.
• Qualified Persons, who certify batches, must ensure samples remain accessible, and will be asked about Section 9 arrangements at inspection.
• Contract packers and re-packaging sites, who need updated written agreements defining who takes and stores each sample.
• Marketing authorisation holders relying on third party release sites, whose Chapter 7 written agreements should be reviewed.
• Non-EEA manufacturers and their EU importers, who must confirm MRA and EEA storage arrangements are still correct.

Annex 19 compliance checklist

Use this checklist to scope a gap assessment against the revised Annex 19 before 24 September 2026.

• Confirm whether your site performs parallel importing, distribution, trading or re-packaging within the scope of Section 9.
• Update sampling SOPs to require a retention sample for each re-packaging operation, kept at least one year after expiry.
• Confirm retention samples include both primary and secondary packaging, with the unopened secondary package rule documented.
• Set up retention of re-packaging materials, labels, carton, leaflet and inserts, for the shelf life of the re-packaged product.
• Confirm all retention samples are stored within the EEA, preferably where the certifying QP is located.
• Review Chapter 7 written agreements so every party sampling and storage duty is defined.
• Verify the QP can access all reference and retention samples at all reasonable times.
• If you plan to use digital samples, prepare the justification, seek prior competent authority agreement, and validate an Annex 11 compliant records system.
• Reconfirm finished product retention at one year after expiry and starting material retention at two years after finished product release.
• Run a documented gap assessment and assign owners and dates to each remediation action.

Common mistakes to avoid

• Assuming the revision is only about digital samples and missing the mandatory Section 9 retention sample per re-packaging operation.
• Treating the photographic option as a free choice rather than a route needing prior competent authority agreement.
• Storing a digital sample without Annex 11 record integrity controls, which invalidates the whole approach.
• Keeping one retention sample across multiple re-packaging runs instead of one per operation.
• Forgetting to retain the re-packaging materials for the full shelf life of the re-packaged product.
• Leaving retention samples outside the EEA when Section 8.1 requires them within it.
• Not updating Chapter 7 written agreements, so no party clearly owns the sampling duty.
• Waiting for a longer transition that does not exist. The applicable date is 24 September 2026, three months after publication.

Frequently asked questions

When does the revised EU GMP Annex 19 come into force?

It becomes applicable on 24 September 2026, three months after the European Commission published it on 24 June 2026 under decision C(2026) 4135 final. There is no additional transition period.

Do I need a reference sample for a parallel imported product?

No. Section 9.2 of the revised Annex 19 states that reference samples of the re-packaged product are not required. You do, however, need a retention sample for each re-packaging operation under Section 9.3.

How long must retention samples be kept?

Retention and reference samples of a finished product must be kept for at least one year after the expiry date. Samples of starting materials, other than solvents, gases and water, must be kept for at least two years after the finished product is released, unless the material stability period is shorter.

Can I keep photographs instead of physical retention samples?

Only in limited circumstances. Section 9.5 allows a photographic or digital sample where it is duly justified that a physical sample cannot reasonably be kept, and only where it has been agreed in advance with the competent authority. The digital record must comply with Annex 11 and must show the safety features and braille information.

Where must retention samples be stored?

Retention samples must in all cases be located within the EEA, and preferably at the site where the Qualified Person certifying the batch is located, so that competent authorities can access them readily.

Does Annex 19 apply to veterinary medicines?

Yes. EudraLex Volume 4 and Annex 19 apply to medicinal products for both human and veterinary use, so veterinary manufacturers, importers and parallel operators are within scope.

How MFLRC can help

The Annex 19 revision maps directly onto MFLRC quality assurance, audit and validation services. We turn the new text into a clear, prioritised and defensible plan rather than a scramble before the deadline.

Our support includes:

• Annex 19 gap assessment against the revised Section 9, your sampling SOPs, your retention arrangements and your supplier qualification records.
• SOP development for sampling, retention and re-packaging controls, aligned with your validation master plan.
• Chapter 7 written agreement review, so every party sampling and storage duty is defined.
• Annex 11 record integrity assessment for any planned photographic or digital retention sample.
• Qualified Person advisory and QP access arrangement review.
• EU importer and parallel distributor readiness audits and mock inspections.

Whether you manufacture in Canada, import into the European Union, or operate as a parallel distributor, our pharmaceutical validation services, audit services and quality assurance support close gaps before they become inspection findings. If you are also preparing for the related Annex 15 revision, we can align the work into one programme.

Conclusion

Annex 19 sat unchanged for twenty years, which is exactly why its revision is easy to underestimate. The new Section 9 gives parallel operators the clear sampling rules they never had, and the digital sample route offers real relief, but only to companies that build the prior authority agreement and the Annex 11 controls to support it. The applicable date of 24 September 2026 is close, and there is no longer transition to wait for. Sites that revise their SOPs and written agreements now will meet their first post-revision inspection with confidence. Those that wait will be explaining gaps to an inspector instead.

Sources and references

• European Commission, EudraLex Volume 4: Reference and Retention Samples (revised, applicable 24 September 2026), news announcement, 24 June 2026.
• European Commission, Commission decision C(2026) 4135 final, revised Annex 19, Brussels, 23 June 2026.
• Directive 2001/83/EC, Article 47, and Commission Directive 2017/1572/EU, the legal basis for the GMP guidelines.
• PIC/S, Pharmaceutical Inspection Co-operation Scheme, joint recommendation with the EU GMP and GDP Inspectors Working Group.