The European Commission has published a revised EudraLex Volume 4, Annex 19: Reference and Retention Samples. The revision was published on 24 June 2026 and is applicable from 24 September 2026. It replaces the 2006 version of Annex 19.
For EU GMP organisations, the immediate issue is not simply document replacement. Annex 19 sits at the intersection of Quality Control, batch certification, product complaints, packaging control, supply-chain oversight and Marketing Authorisation Holder (MAH) governance. The revised text particularly addresses retention arrangements for parallel imported, parallel distributed and parallel traded products, but it also provides a timely reason to test whether the wider sample-management system is controlled, accessible and contractually coherent.
What Annex 19 covers
Annex 19 gives guidance on taking and holding:
- Reference samples of starting materials, packaging materials or finished products, kept so that analysis can be performed if needed during the relevant batch shelf life.
- Retention samples of finished product, kept as fully packaged units for identification purposes, including examination of presentation, packaging, labelling, leaflet, batch number and expiry date.
For many finished products, the two sample types are identically presented as fully packaged units and may be treated as interchangeable. That does not remove the need to understand the distinct purposes: one supports potential analytical testing; the other supports identification and investigation of the product placed on the market.
The Annex states that sample traceability records should be maintained and available for competent-authority review. It also identifies the kinds of events in which samples may be assessed: dosage-form quality complaints, questions about compliance with the marketing authorisation, labelling or packaging queries, and pharmacovigilance reports.
Regulatory facts that remain central
The revised Annex continues to set out the expected retention periods, sample sizes, storage arrangements and allocation of responsibilities.
| Area | Annex 19 expectation |
|---|---|
| Finished-product samples | Reference and retention samples from each batch should be retained for at least one year after expiry. The reference sample should be in finished primary packaging, or packaging of the same material as the marketed primary container. |
| Starting-material samples | Unless Member State law requires longer, samples should be retained for at least two years after release of the finished product. The period may be shortened where the relevant specification gives a shorter stability period. Solvents, gases and water used in manufacture are excluded from this provision. |
| Packaging materials | Packaging materials should be retained for the shelf life of the finished product concerned. |
| Reference-sample quantity | The quantity should permit full analytical controls, in accordance with the approved Marketing Authorisation file, on at least two occasions. |
| Storage | Conditions should comply with the marketing authorisation, including refrigerated conditions where relevant. |
There are important operational qualifications. Reference samples should be representative of the batch from which they are taken. If a batch undergoes two or more distinct packaging operations, at least one retention sample should be taken from each packaging operation, unless an exception is justified and agreed with the relevant competent authority. The Annex also says that necessary analytical materials and equipment should remain available, or readily obtainable, until one year after expiry of the last batch manufactured.
Written agreements and QP access
The revised Annex retains a clear emphasis on written agreements. Where the MAH and the EEA batch-release site are not the same legal entity, responsibility for taking and storing reference and retention samples should be defined in a written agreement in accordance with Chapter 7 of the EU GMP Guide.
The same principle applies where manufacturing or batch-release activities occur at sites other than the site with overall responsibility for the batch on the EEA market. In multi-site networks, agreements should establish where samples are taken, which samples are held at which location, who maintains traceability, who authorises retrieval or destruction, and how access is assured during an investigation.
The Annex specifically states that the Qualified Person (QP) certifying a batch for sale should ensure that relevant samples are accessible at all reasonable times. This is a practical release-system consideration: QP oversight should not depend on informal assumptions about a contract manufacturer, importer, packager or third-party archive provider holding the required material.
The principal revision: parallel-imported, parallel-distributed and parallel-traded products
The stated reason for revision is a joint recommendation by the GMP/GDP Inspectors Working Group and the PIC/S Committee concerning reference and retention samples for parallel imported, parallel distributed and parallel traded products. Section 9 of the new Annex introduces specific expectations for re-packaged product.
For these products, physical samples of packaging materials used in re-packaging, such as labels, cartons, patient information leaflets and other inserts, should be retained for the shelf life of the re-packaged finished product. Reference samples of the re-packaged product are not required.
However, a retention sample of the re-packaged finished product should be taken for each re-packaging operation and retained for at least one year after expiry. It should represent the product released to the market and include both primary and secondary packaging. Where the secondary pack is not opened, only the packaging material used needs to be retained.
The Annex permits a photographic or digital sample only where retaining a physical sample cannot reasonably be achieved, the rationale is duly justified, and the arrangement has been agreed in advance with the competent authority. The digital record must allow a full visual examination and an investigation equivalent to that available from a physical sample. It must be traceable to the relevant batch packaging record and include primary and secondary packaging information, including batch number and expiry date. It must also evidence applied safety features and permit identification of braille information. Electronically stored records should comply with Annex 11 principles to preserve record integrity throughout the retention period.
What to do before 24 September 2026
GuideGxP recommendation: use the period before applicability to run a focused, cross-functional gap assessment rather than treating this as a QC-only update.
- Map the sample lifecycle. Identify every point at which starting-material, packaging-material, reference and retention samples are taken, transported, stored, accessed, reconciled and destroyed.
- Segment product flows. Separate conventional manufacture, importation, multi-site packaging and parallel import/distribution/trade scenarios. Confirm which Annex 19 section governs each flow.
- Review SOPs and batch documentation. Ensure procedures define sample identity, representativeness, quantities, packaging configuration, storage conditions, reconciliation, traceability and investigation retrieval.
- Test technical agreements. Check alignment among the MAH, manufacturer, importer, batch-release site, packaging site and any archive provider. Agreements should make responsibilities and QP access demonstrable.
- Assess digital-sample controls. Where a photographic or digital sample may be used, establish an approved exception pathway, competent-authority engagement process, record specification and Annex 11-aligned integrity controls.
- Verify business-continuity arrangements. For product transfers, site closures or changes in manufacturing authorisation, make sample and GMP-document transfer arrangements explicit before a disruption occurs.
Supply-chain and inspection implications
Sample governance is often dispersed across Quality Assurance, QC laboratories, packaging operations, supply-chain functions and external partners. That dispersion is itself a compliance risk. A retained sample that exists but cannot be located quickly, linked unambiguously to the right batch and packaging operation, or accessed by the QP does not provide the intended assurance during a complaint, recall assessment or authority inspection.
GuideGxP recommendation: build a single controlled inventory view that links the sample identifier to batch records, market presentation, storage location, expiry-based retention date, relevant agreements and, where applicable, the associated digital record. This is an operational design choice, not an additional explicit Annex 19 requirement, but it makes the Annex’s expectations for traceability and ready access easier to demonstrate.
