The European Commission has published a revised version of EU GMP Annex 19, Reference and Retention Samples. The new text was issued on 24 June 2026 under Commission Decision C(2026) 4135 and becomes applicable on 24 September 2026, three months after publication. It replaces the 2006 version that has been in force since 1 June 2006.
For many manufacturers, the update will not change the basic reference-and-retention sample model. The established requirements for sample purpose, storage duration, sample size, storage conditions, written agreements, and closure arrangements remain largely stable.
The real change is concentrated in Section 9. This section has been expanded to cover parallel-imported, parallel-distributed, and parallel-traded products, with more prescriptive expectations for re-packaging materials, retention samples from re-packaging operations, and the controlled use of photographic or digital retention samples.
For companies involved in parallel trade, batch release, re-packaging, packaging material control, or QP certification, this revision should trigger a focused SOP review before the application date. Here is what changed, what stayed the same, and what you need to do before 24 September.
The Short Version
- The reason for the revision is parallel trade. The GMP/GDP Inspectors Working Group and the PIC/S Committee recommended updating the annex specifically for reference and retention samples of parallel-imported, parallel-distributed, and parallel-traded products.
- Section 9, which deals with parallel trade, has been rewritten and expanded from two short paragraphs into a structured set of requirements.
- A new option has been introduced: a photographic or digital retention sample, allowed only under defined conditions and with prior agreement from the competent authority.
- Sections 1 to 8 and Section 10, covering the everyday reference and retention sample regime, are substantively unchanged.
- The legal basis has been updated to reflect Directive 2017/1572/EU, and outdated cross-references have been corrected.
What Is Annex 19 About?
Annex 19 defines how reference and retention samples should be taken and held under EU GMP. The annex separates two sample concepts that are sometimes confused in practice:
Reference samples are retained primarily for analytical testing. They may be used to test a batch during its shelf life, for example, during a quality investigation, complaint, or regulatory query.
Retention samples are kept as specimens of the fully finished product. Their purpose is mainly visual and documentary. They allow verification of presentation, packaging, labeling, patient information leaflet, batch number, expiry date, and other non-analytical product attributes.
In many cases, the reference sample and retention sample may look identical because both are stored as fully packaged units. However, their intended purposes differ, and that difference becomes important in the revised Section 9.
Related Article: Difference between Reference and Retention Samples
What Did Not Change for Reference and Retention Samples
If your site does not perform parallel trade re-packaging, the operational impact is limited. The following remain as they were in the 2006 text:
- Reference and retention samples of the finished product are retained for at least 1 year after the expiry date.
- Starting material samples are retained at least two years after release of the finished product, unless stability supports a shorter period.
- Reference sample size sufficient for full analytical controls on at least two occasions.
- Storage conditions in line with the marketing authorization.
- Written agreements between the marketing authorization holder, batch release site, and any other sites involved.
- The closedown provisions in Section 10, including transfer of samples and the obligations of the importer and the MAH.
For these areas, the action is administrative: update document references, not procedures.
The Main Change: Parallel Trade Re-Packaging (Section 9)
The old Section 9 handled parallel trade with two risk-based paragraphs. The revised Section 9 sets out explicit, prescriptive requirements. The changes break down into five points.
| Area | What Changed | Practical GMP Impact |
|---|---|---|
| Re-packaging materials | Physical samples of labels, cartons, PILs, inserts, and other re-packaging materials must be retained for the shelf life of the re-packaged product. | Packaging material retention becomes more prescriptive and may require updates to storage, indexing, and batch record traceability. |
| Reference samples | Reference samples of the re-packaged product are not required. | Companies should remove unnecessary local requirements for reference samples of re-packaged products unless separately justified. |
| Retention samples | A retention sample must be taken for each re-packaging operation. | Sampling should be linked to the actual re-packaging operation, not only to the product or batch number. |
| Retention period | Retention samples of re-packaged finished products must be kept for at least one year after expiry. | SOPs should clearly define the retention period and avoid shorter local retention practices. |
| Sample composition | The retention sample should represent the released re-packaged product, including primary and secondary packaging where applicable. | The sample should support later verification of labelling, batch number, expiry date, safety features, Braille information, and market presentation. |
| Digital retention samples | A photographic or digital sample may be used only when a physical sample cannot reasonably be retained and this is agreed in advance with the competent authority. | Digital samples should be treated as an exception, supported by justification, authority agreement, and a controlled process. |
| Annex 11 link | Electronically stored photographic or digital samples must comply with Annex 11 principles. | Access control, traceability, backup, retrieval, retention, and protection from uncontrolled changes should be defined. |
Change 1: Section 9 now covers parallel traded products
The previous Annex 19 referred to parallel-imported and parallel-distributed products. The revised Section 9 broadens its wording to include parallel-traded products as well.
This is not only a terminology update. Companies should check whether all relevant product flows are actually covered. A local procedure that only refers to “parallel import” may not be broad enough if the company also handles parallel distribution or parallel trade through different commercial or regulatory routes.
At minimum, review:
- Scope of the reference and retention sample SOP
- Re-packaging SOPs
- Packaging material retention procedures
- Batch packaging record requirements
- Quality agreements between MAH, re-packager, importer, batch release site, and storage site
- Responsibilities of the QP for sample availability
Change 2: Re-Packaging Materials Must Be Physically Retained
The revised annex makes retention of re-packaging materials explicit. Physical samples of packaging materials used in re-packaging should be retained for the full shelf-life of the re-packaged finished product.
This may include:
- Labels
- Cartons
- Patient information leaflets
- Package inserts
- Other printed or non-printed packaging materials used during re-packaging
The retained materials support later investigation of packaging and labeling issues, such as a complaint, a suspected mix-up, a printing issue, a market-specific labeling query, a safety feature concern, or a question about compliance with the marketing authorization.
Check whether your current procedures already require retention of all re-packaging materials, or only selected materials based on risk. The revised wording is more prescriptive, so local procedures may need to be updated.
Change 3: Reference Samples of the Re-Packaged Product Are Not Required
The revised annex states that reference samples of the re-packaged product are not required.
The re-packaged product has usually already been manufactured and released as a finished product. In re-packaging, the GMP concern is not normally repeated analytical testing of the re-packaged unit, but whether the released market presentation can be verified later. That is why the annex focuses on retention samples and re-packaging materials rather than reference samples here.
Change 4: A Retention Sample Is Required for Each Re-Packaging Operation
The revised annex states that 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 the expiry date.
The requirement is linked to each re-packaging operation, not only to the product name or batch number. The same product may be repackaged in different operations, for different markets, with different printed materials, language versions, or operational conditions.
The retention sample should represent the re-packaged finished product as released to the market, and should include:
- The primary package
- The secondary package
- Market-specific packaging materials
- Batch number
- Expiry date
Where the secondary package is not opened during re-packaging, the annex allows only the packaging material used to be retained.
See Also: Primary vs Secondary Packaging in Pharmaceutical Industry
Change 5: Photographic or Digital Retention Samples Are Now Possible in Specific Cases
A photographic or digital retention sample may be used only where a physical retention sample of the re-packaged finished product cannot reasonably be retained. This must be justified and agreed in advance with the competent authority. It is not a general storage-saving alternative to physical samples.
Where the option is used, the photographic or digital sample must:
- Be a complete record that allows full visual examination and supports investigation to the same standard as a physical sample
- Consists of high-quality photographs of the re-packaged product
- Allow traceability to the batch packaging record for that specific re-packaged product
- Capture all data on both primary and secondary packaging, such as batch number and expiry date
- Show evidence that the safety features have been applied and allow identification of information in braille
- Comply with Annex 11 where stored electronically, so that record integrity is maintained over the full retention period
Corrected and Modernized References
The revision also tidies up references that had aged:
- The cross-reference for investigational medicinal products now points to the Detailed Commission guideline on GMP for investigational medicinal products, replacing the reference to Annex 13.
- The veterinary cross-reference to Annex 4 in the storage clause has been removed, reflecting the separate veterinary GMP framework.
- The starting material retention clause now reads “two years after the release of the finished product,” a small wording clarification.
- The legal basis is restated under Article 47 of Directive 2001/83/EC and Commission Directive 2017/1572/EU.
What You Need to Do Before 24 September 2026
The annex becomes applicable three months after publication. Use that window to work through the following:
- Update SOP references. Cite C(2026) 4135 and Directive 2017/1572/EU. Correct the investigational medicinal product cross-reference and remove the obsolete Annex 4 reference.
- Revise parallel trade and re-packaging procedures. Build in the explicit retention requirements for re-packaging materials, the per-operation retention sample, the one-year-post-expiry duration, and the primary-plus-secondary sample composition.
- Decide on the digital sample option. If you intend to use it, start the conversation with your competent authority now. Prepare the justification and define acceptance criteria, photo quality standards, traceability, and Annex 11-compliant storage.
- Confirm scope. Check whether parallel traded products, now named explicitly, are captured by your existing procedures.
- Plan and document the transition. Treat the implementation as a controlled change with a target completion date inside the three-month window.
Bottom line
The 2026 revision of Annex 19 is targeted, but it should not be ignored by companies involved in parallel trade and re-packaging.The core reference and retention sample framework remains largely unchanged. The important update is the clearer, more prescriptive control over repackaged products, packaging materials, and digital retention samples.
The new photographic or digital sample option may be useful in specific, justified cases, but it also brings additional expectations. Once a digital image becomes the retained GMP record, the company must control it with the same seriousness as any other regulated electronic record.
For QA teams, QPs, re-packaging sites, importers, and MAHs, the priority is clear: review Section 9, update procedures, clarify responsibilities, and make sure the sample retention process can support future investigations, inspections, and regulatory queries.
