- Annex 8 of EudraLex Volume 4, titled Sampling of Starting and Packaging Materials, provides specific Good Manufacturing Practice (GMP) guidelines on the procedures and controls associated with the sampling of raw materials and packaging components used in the manufacture of medicinal products. The annex outlines essential requirements to ensure that the materials received by a manufacturer meet the established quality standards before being used in production. It reinforces the principle that proper sampling is a critical quality control activity, serving as the foundation for verifying the identity, purity, and compliance of incoming materials.
- One of the core tenets of Annex 8 is that each batch of starting materials must be sampled and tested for conformity with established specifications before use, unless otherwise justified and documented through a validated supplier qualification program. Sampling must be done in accordance with written procedures that specify the method, quantity, sampling location, equipment to be used, and precautions to prevent contamination or cross-contamination. The sampling plan must be based on a risk assessment, considering the material’s origin, nature, and criticality in the final product.
- Annex 8 distinguishes between starting materials (such as active pharmaceutical ingredients and excipients) and primary and printed packaging materials (such as blister foils, bottles, labels, etc.), both of which require careful handling and inspection. It emphasizes that materials should be sampled only by trained personnel, using clean and dedicated equipment, in designated sampling areas. These areas should provide environmental conditions appropriate to the type of material being handled (e.g., control of dust or microbial contamination), especially in cases involving potent, toxic, or sensitive substances.
- The annex permits the use of reduced sampling plans for certain materials, such as those from well-established, qualified suppliers, where a history of compliance, supply chain control, and consistent quality has been demonstrated. This approach must be supported by documented quality risk management (QRM) processes and periodic verification through full testing. Nonetheless, the identity testing of each container of active substances is mandatory unless the manufacturer has established and validated that a representative sampling strategy provides equivalent assurance.
- For printed packaging materials, Annex 8 insists on 100% visual inspection for critical elements such as labeling, product name, batch number, and expiry date to avoid mix-ups that could compromise patient safety. Sampling should be performed in a way that preserves the quality and usability of the materials not tested, and all sampled materials must be properly labeled, traced, and quarantined until testing and approval are complete.
- The annex also outlines the requirements for sample retention, stating that sufficient quantities should be retained to allow for repeat testing or investigation of quality issues. These samples must be stored under conditions that ensure their stability and protect them from degradation.
- In summary, EudraLex Volume 4 – Annex 8 provides detailed and practical GMP guidance for the sampling of starting and packaging materials, highlighting its importance as a preventive measure in ensuring product quality. By defining how, where, and under what conditions sampling should take place, the annex supports a robust quality system that enables the detection of substandard or non-compliant materials before they enter the manufacturing process. This contributes directly to the overall assurance of patient safety, product efficacy, and regulatory compliance across the pharmaceutical supply chain.
Further reading:
- EudraLex – Volume 4 – Good Manufacturing Practice (GMP) guidelines
- EudraLex – The Rules Governing Medicinal Products in the European Union, Volume 4 EU Guidelines for Good Manufacturing Practice for Medicinal Products for Human and Veterinary Use Annex 8: Sampling of Starting and Packaging Materials
