- Annex 5 of EudraLex Volume 4, titled Manufacture of Immunological Veterinary Medicinal Products, provides specific Good Manufacturing Practice (GMP) requirements for the production of immunological veterinary medicinal products (IVMPs). These include a wide range of biologically derived veterinary vaccines and immunotherapeutics, such as live and inactivated vaccines, autogenous vaccines, antitoxins, and diagnostic agents intended for animal use. Given the complex nature of these products and their origin from biological sources, Annex 5 offers tailored guidance that addresses their unique production and quality control challenges.
- The annex begins by emphasizing that IVMPs require a high level of control and oversight throughout all stages of manufacturing, due to the potential variability of biological materials and the associated risks of contamination with adventitious agents. It applies to both commercial and non-commercial (e.g., autogenous) production, and includes guidance for all key production stages—from the preparation and handling of cell cultures or bacterial strains, to fermentation, purification, formulation, filling, and packaging.
- A central component of Annex 5 is the management of seed lots and cell banks, which form the biological foundation of many immunological products. The annex outlines strict requirements for the establishment, identification, testing, storage, and traceability of master seed lots, working seed lots, and cell substrates. These materials must be characterized for identity, purity, and freedom from contamination (e.g., viruses, mycoplasma, and other microorganisms), and must be stored under carefully controlled conditions to ensure their genetic and phenotypic stability over time.
- The annex also sets expectations for facility and equipment design, with a strong focus on segregation and containment to avoid cross-contamination, particularly when manufacturing live vaccines or multiple antigenic products in the same facility. Zoning, use of dedicated equipment, and specific airflow and pressure differentials are expected for different manufacturing areas. The use of closed systems and validated decontamination procedures is encouraged to protect both the product and the personnel.
- Aseptic processing is particularly important in the production of immunological veterinary products, especially those that cannot undergo terminal sterilization. Annex 5 requires rigorous control of environmental conditions, routine monitoring, and process validation to ensure sterility and product integrity. Personnel training is another key focus, with manufacturers expected to ensure that all staff involved in production and quality control are trained in both GMP and biosafety procedures.
- Regarding quality control, Annex 5 mandates extensive in-process and final product testing, including tests for identity, potency, sterility, safety, and freedom from extraneous agents. Stability studies are required to define the product’s shelf life, and special attention must be given to establishing withdrawal periods for food-producing animals to ensure no harmful residues remain in meat, milk, or eggs.
- The annex also includes guidance for the manufacture of autogenous vaccines—custom-made vaccines prepared from pathogens isolated from individual animals or herds. While these products are typically produced in smaller volumes and may not be subject to the same level of regulation as commercial vaccines, Annex 5 still requires adherence to core GMP principles, including traceability, documentation, and biosafety.
- In summary, EudraLex Volume 4 – Annex 5 provides comprehensive GMP guidance specifically for immunological veterinary medicinal products, recognizing the biological complexity and public health implications of these products. It ensures that vaccines and related biologics for animals are manufactured under strict quality and safety controls, not only to protect animal health, but also to safeguard the food supply, prevent zoonotic disease transmission, and support the responsible use of biologicals in veterinary medicine.
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 5: Manufacture of Immunological Veterinary Medicinal Products
