The European Commission published the revised Annex 19 – Reference and Retention Samples on 24 June 2026. The revised text is listed in EudraLex Volume 4 as applicable from 24 September 2026. It revises the 2006 version of Annex 19 and introduces a dedicated section on reference and retention samples for parallel imported, parallel distributed and parallel traded products.
For senior GMP leaders, this is not simply a document-control update. Annex 19 sits at the intersection of batch release, product-quality complaint investigation, packaging and labelling verification, pharmacovigilance follow-up, importation controls and market supply continuity. Sample availability, condition, identity and traceability are all readily testable during an inspection.
What the revised Annex 19 covers
Annex 19 provides guidance on taking and holding reference samples of starting materials, packaging materials and finished products, together with retention samples of finished products. It distinguishes the two sample types by purpose:
- Reference samples are retained so that analysis can be performed if needed during the relevant batch shelf life.
- Retention samples are fully packaged finished-product units retained for identification purposes, including the presentation, packaging, labelling, patient information leaflet, batch number and expiry date.
For finished products, the two may be identically presented and therefore interchangeable in many cases. However, the site’s rationale, inventory model and retrieval arrangements should make clear that both intended purposes can be fulfilled when a sample is requested.
The Annex also states that records supporting sample traceability should be maintained and available to competent authorities. This means a sample store is not adequately controlled merely because units can be located physically; the organisation also needs a reliable evidence trail from batch and packaging operation to stored sample, location, status and eventual disposition.
Regulatory facts: core controls that remain central
The revised Annex maintains familiar expectations on retention periods, sample quantities, storage and responsibilities. Finished-product reference and retention samples are to be retained for at least one year after expiry. Starting-material samples, other than solvents, gases or water used in manufacture, are retained for at least two years after release of the finished product unless Member State law requires longer; the period may be shorter where the material’s specified stability period is shorter. Packaging materials are retained for the shelf life of the relevant finished product.
A reference sample should permit at least two full sets of analytical controls in accordance with the Marketing Authorisation File assessed and approved by the relevant competent authority or authorities. Reference samples should be representative of the relevant batch. Where packaging occurs through two or more distinct packaging operations, at least one retention sample should be taken from each operation, unless an exception is justified and agreed with the relevant competent authority.
Storage conditions must align with the marketing authorisation where applicable. The Annex also expects the ongoing availability, or ready obtainability, of the analytical materials and equipment required to conduct specification testing until one year after expiry of the last batch manufactured.
| Control area | Annex 19 focus | Practical question for the site |
|---|---|---|
| Sample purpose | Analysis versus identification | Can the sample strategy support both complaint investigation and full analytical testing where required? |
| Traceability | Records available to competent authorities | Can QA retrieve the batch-to-sample history, location and status without manual reconstruction? |
| Storage | Conditions consistent with the marketing authorisation | Do mapping, monitoring, excursion handling and capacity controls cover every sample location? |
| Testing capability | Materials and equipment remain available | Is analytical-method and reagent lifecycle planning connected to the sample-retention period? |
What changes for parallel imported, parallel distributed and parallel traded products
The principal new content is section 9, “Reference and Retention Samples for Parallel Imported/Parallel Distributed/Parallel Traded Products”. It addresses products that are re-packaged and clarifies the evidence expected from the re-packaging operation.
Physical samples of packaging materials used in re-packaging, such as labels, cartons, patient information leaflets and other package inserts, should be retained for the shelf life of the re-packaged finished product. Reference samples of the re-packaged product are not required. A retention sample of the re-packaged finished product should instead be taken for each re-packaging operation and retained for at least one year after expiry.
The retention sample is expected to represent the re-packaged product released to market and include both primary and secondary packaging. If the secondary pack is not opened, the packaging material used is to be retained. The Annex permits a photographic or digital sample only where physical retention cannot reasonably be achieved, the situation is duly justified, and prior agreement has been obtained from the competent authority.
Where electronic photographic or digital samples are used, Annex 19 explicitly links record integrity over the retention period to the principles of Annex 11. The record needs to enable full visual examination and equivalent investigation, show relevant primary and secondary packaging data, support traceability to the applicable batch packaging record, demonstrate applied safety features and permit identification of braille information.
Written agreements and QP accessibility
Annex 19 requires responsibilities for taking and storing samples to be defined in written agreements where the Marketing Authorisation Holder and the EEA batch-release site are different legal entities. It also addresses arrangements where manufacturing or batch-release activities occur at sites other than the site with overall responsibility for the batch on the EEA market.
The QP certifying a batch for sale should ensure that relevant reference and retention samples are accessible at all reasonable times. This is especially important in networks involving contract manufacturers, importers, packaging sites, laboratories and third-party sample-storage providers. A technically sound agreement that does not provide usable access during an investigation will not deliver the intended control.
GuideGxP recommendation: complete a focused implementation assessment
The following actions are practical GuideGxP recommendations, not additional regulatory requirements. They are designed to help organisations demonstrate a controlled transition before 24 September 2026.
- Map the end-to-end sample lifecycle. Include sampling, labelling, transport, storage, monitoring, retrieval, use, reconciliation, destruction and data retention. Map each activity to the legal entity and GMP-authorised site performing it.
- Segment the portfolio. Identify conventional finished products, imported products, products under an operational MRA arrangement, multi-site packaging configurations and parallel imported/distributed/traded products. Do not assume one SOP workflow adequately covers every model.
- Review sample plans against approved product information. Confirm retention duration, quantity, packaging configuration, storage condition and test capability against the relevant marketing authorisation and current specifications.
- Assess digital sample records under Annex 11 principles. For any photographic or digital retention model, assess governance for access, attribution, completeness, review, secure retention, retrieval, backup and change control. Document how the record supports the required visual examination and batch traceability.
- Update quality agreements and escalation routes. Make responsibilities, storage locations, retrieval targets, authority interaction and closedown arrangements unambiguous. Test the process with a realistic complaint or labelling-investigation scenario.
- Train the operational interfaces. QA, QP, QC, packaging, warehousing, supply chain and Regulatory Affairs should understand which records and physical samples they own, and what must be rapidly available during an inspection or investigation.
Inspection-ready evidence
An effective readiness package should allow the site to show a current gap assessment, approved change controls, revised SOPs and sample plans, updated written agreements, training evidence, storage qualification and monitoring evidence, inventory and traceability records, and a documented assessment of any digital-retention approach. For parallel-trade operations, it should also make the justification and competent-authority agreement available where a physical retention sample is not reasonably retained.
The revised Annex 19 should be treated as an opportunity to test whether sample governance works across organisational boundaries. The strongest implementation outcome is not a revised procedure alone; it is a demonstrable ability to retrieve the correct sample and its supporting record, in the correct condition, when product quality or patient protection requires it.
