- Annex 4 of EudraLex Volume 4, titled Manufacture of Veterinary Medicinal Products Other Than Immunologicals, provides specific Good Manufacturing Practice (GMP) guidance for the production of veterinary pharmaceuticals, excluding immunological veterinary medicinal products (which are covered under Annex 5). This annex addresses the unique aspects of veterinary medicine manufacturing, while ensuring that products are consistently produced and controlled to meet the required standards of quality, safety, and efficacy for animal use. It aligns with the general GMP principles outlined in Part I of EudraLex Volume 4 but adapts them to reflect the distinct requirements of veterinary products, which can differ significantly in formulation, dosage, batch size, and use compared to human medicines.
- A key focus of Annex 4 is to ensure that manufacturers adopt fit-for-purpose quality systems that account for the diverse nature of veterinary medicinal products. These include oral dosage forms (such as premixes and medicated feeds), topical applications, injectables, and intramammary preparations. The annex recognizes that veterinary drugs may be produced in large volumes for use in farm animals or in small volumes for pets, and thus offers flexibility in applying GMP requirements based on product type, risk level, and intended species.
- The annex emphasizes the need for appropriate facility design, process control, and documentation, especially where products are formulated in ways that pose a risk of cross-contamination—for example, in manufacturing beta-lactams or other potent veterinary actives. Dedicated or segregated areas may be required for such products. Equipment must be suitably designed and maintained, and cleaning validation is essential to prevent contamination between batches or products.
- Annex 4 also stresses the importance of raw material control, particularly when using active substances or excipients derived from animal origin, which carry the potential risk of transmitting transmissible spongiform encephalopathies (TSEs). In such cases, materials must comply with relevant EU guidelines and sourcing requirements. Furthermore, the annex calls for detailed in-process and final product testing, including routine checks for homogeneity in medicated premixes and stability data to support shelf life and withdrawal periods (time after administration during which animals cannot be slaughtered for food).
- The control of labels and packaging materials is also addressed, particularly because errors in labeling for veterinary medicines can have serious consequences for animal health, food safety, and the environment. As such, Annex 4 requires clear procedures to ensure that correct labels, batch numbers, and expiry dates are applied, and that packaging materials are appropriately handled and stored.
- While Annex 4 focuses on non-immunological veterinary products, it maintains the overarching regulatory goal of protecting both animal health and public health, especially given the role of veterinary medicines in the food chain. The annex supports compliance with EU regulations related to veterinary public health, antimicrobial resistance (AMR), and residue limits in food-producing animals.
- In summary, EudraLex Volume 4 – Annex 4 provides a specialized GMP framework tailored for the manufacture of veterinary medicinal products other than immunologicals. It acknowledges the practical and scientific differences between veterinary and human medicines, offering flexibility where justified, while maintaining a strong focus on quality control, contamination prevention, and public health safeguards. By doing so, it helps ensure that veterinary drugs are manufactured in a safe, reliable, and compliant manner across the European Union.
