Key regulatory changes and practical implications for organisations involved in parallel importation, distribution, trade and repackaging.
The European Commission has revised EU GMP Annex 19 – Reference and Retention Samples. The new version has been applicable since 24 September 2026, replacing the previous text in force since 2006.
While the fundamental principles governing reference and retention samples remain unchanged, the revision introduces important clarifications and additional expectations, particularly for medicinal products involved in parallel importation, parallel distribution, parallel trade and repackaging activities.
For organisations operating in these areas, the revision goes beyond a simple update to existing procedures. It provides an opportunity to reassess sampling strategies, packaging-material controls, traceability arrangements and electronic record management to ensure continued GMP compliance and inspection readiness.
In this article, PLG experts Faiza Tahanout and Giulia Cacioppa explain what has changed, where the main compliance risks lie and what quality teams should review now.
Although often managed together, reference and retention samples serve distinct purposes within the pharmaceutical quality system.
Reference samples are samples of starting materials, packaging materials or finished products retained to enable analytical testing, should a quality concern arise during the batch shelf life. The quantity retained should be sufficient to permit at least two full analytical examinations, unless a justified exception applies.
Retention samples are fully packaged units of finished products retained primarily for identification and visual examination. They provide evidence of the product presentation as placed on the market, including primary and secondary packaging, labelling, patient information leaflets, batch number and expiry date.
Understanding this distinction is essential: reference samples support analytical investigations, whereas retention samples provide evidence of the marketed product presentation. Consequently, sampling procedures, storage conditions and assigned responsibilities must reflect these different objectives.
Most requirements in Sections 1 to 8 and Section 10 remain substantially unchanged. These include expectations concerning sample quantities, retention periods, storage conditions, quality and technical agreements, allocation of responsibilities and arrangements following site closure.
The most relevant changes are concentrated in Section 9, which addresses specific considerations for repackaging and related activities .
The key updates include:
The revised Annex explicitly addresses medicinal products involved in parallel importation, parallel distribution and parallel trade, providing greater clarity on the expectations applicable to these activities.
Physical samples of all packaging materials used during repackaging operations must be retained for the shelf life of the repackaged product. This includes labels, cartons, patient information leaflets and other package inserts.
The revised Annex clarifies that reference samples of the repackaged finished product are not required.
A retention sample should be maintained for every repackaging operation for at least one year after the product expiry date.
Where the secondary packaging is not opened during the operation, only the packaging materials used need to be retained.
Where retaining a physical sample of the repackaged finished product is not reasonably practicable, a digital or photographic alternative may be considered, subject to prior agreement with the competent authority.
One of the most significant developments introduced by the revised Annex 19 is the possibility of using photographic or digital samples instead of physical retention samples under specific circumstances.
For organisations managing large volumes of repackaging operations, multiple packaging configurations or significant storage requirements, this option may offer tangible operational benefits.
However, digital retention is not an automatic alternative to physical samples. Under Section 9.5, it may only be used where it is duly justified that retaining a physical sample is not reasonably practicable and prior agreement has been obtained from the competent authority.
The revised Annex also establishes specific requirements for the content and reliability of photographic or digital records.
In particular, the digital sample must:
Data integrity is another essential consideration.
Under Section 9.5.4, photographic or digital samples stored electronically must comply with the principles of EU GMP Annex 11to ensure the integrity of the record throughout the retention period.
In practice, companies should assess the controls needed to protect electronic records, including appropriate access management, audit trails, backup and recovery arrangements,data protection and reliable retrieval throughout the retention period.
The image-capture process should also be standardised through appropriate internal procedures, defining technical parameters that ensure consistent image quality and complete visual examination.
A documented justification and risk assessment should support the proposed approach, while responsibilities for image creation, review, approval, storage and retrieval should be clearly assigned.
Digital retention can therefore represent a valuable opportunity for operational optimisation, provided that regulatory requirements, competent authority agreement and data-integrity principles remain central to its implementation.
The revised Annex 19 provides a timely opportunity for organisations to assess whether their current quality systems and operational arrangements remain appropriate.
A comprehensive gap assessment should consider the entire lifecycle of reference samples, retention samples and packaging materials, from collection and identification through storage, retrieval and final disposal.
Particular attention should be given to the following areas:
Sampling procedures and traceability
Verify that procedures clearly define the materials to be retained, applicable retention periods, storage conditions and documentation requirements. Records should ensure an unambiguous link between the original batch, each repackaging operation and the medicinal product subsequently placed on the market.
Responsibilities and quality agreements
Review the interfaces between manufacturers, importers, distributors, repackaging sites and external service providers. Responsibilities for sampling, storage, record maintenance and retrieval should be clearly assigned and reflected in relevant quality or technical agreements.
Outsourced activities and site closure
Confirm that appropriate arrangements are in place when samples are stored at different locations or activities are outsourced. Procedures should also address changes in contractual arrangements, site closure and the transfer of samples and records to another organisation.
Digital retention and data integrity
For companies considering digital or photographic retention, assess the suitability of the proposed solution against EU GMP Annex 11 expectations. Image quality, metadata, access controls, audit trails, backup, long-term readability and timely retrieval should all be addressed.
Importantly, the documented justification, risk assessment and prior agreement of the competent authority should be available before implementing a digital alternative.
The revised EU GMP Annex 19 does not fundamentally redesign the existing framework for reference and retention samples. However, it provides greater clarity on repackaging activities and introduces specific expectations that organisations involved in these operations should carefully evaluate.
For pharmaceutical companies, the priority should be to translate these regulatory clarifications into effective procedures, clearly defined responsibilities and demonstrable controls within the Pharmaceutical Quality System.
A proactive assessment can help identify compliance gaps, improve operational efficiency and strengthen inspection readiness before regulatory expectations become inspection findings.
At ProductLife Group, our Quality & Compliance experts help manufacturers, importers, distributors and repackagers turn regulatory updates into workable quality systems. For the revised Annex 19, this can include a gap assessment of current sampling and retention procedures, a review of quality and technical agreements across the supply chain, and the design of a risk-based approach to digital retention, from image-capture procedures to EU GMP Annex 11 data-integrity controls, supported by our Digital Quality team. Where needed, our Quality Assurance and Qualified Person services can also provide hands-on support to your quality organisation.
Life Sciences professional with over 10 years of experience in pharmaceutical quality, compliance, and the strategic management of manufacturing activities and projects.
Life Sciences professional with a Doctor of Pharmacy degree and over 3 years of experience in pharmaceutical quality assurance, GMP compliance, product quality complaints management, and Quality Management Systems (QMS).
European Commission, EudraLex Volume 4, Annex 19: Reference and Retention Samples, Commission Decision C(2026) 4135 final.
European Commission, EudraLex Volume 4 – Reference and Retention Samples revised, applicable as of 24 September 2026, 24 June 2026.