Prevention of cross-contamination
Article 29
1. The production of non-medicinal products shall generally be avoided in areas and with equipment destined for the production of veterinary medicinal products, unless measures to prevent cross-contamination are applied in an effective manner. In particular, the production or storage of chemical substances used in biocides and plant protection products shall be avoided in areas used for the manufacture or storage of veterinary medicinal products, except where the same substance and its grade is also used for manufacture of veterinary medicinal products. 2. Where veterinary medicinal products are produced in an area shared with non-medicinal products, good manufacturing practice for medicinal products shall be implemented in the area. 3. Operations on different products shall not be carried out simultaneously or consecutively in the same room unless there is no risk of mix-up or cross-contamination. 4. Before any manufacturing operation starts, steps shall be taken to ensure that the work area and the equipment are clean and free from any materials, products, product residues or documents not required for the current operation. Mix-ups of materials shall be prevented. 5. At every stage of production, products and materials shall be protected from microbial and other contamination. The risk of cross-contamination shall be assessed having regard to the characteristics of the product and the manufacturing process. The risk of accidental cross-contamination resulting from the uncontrolled release of dust, gases, vapours, aerosols, genetic material or organisms from active substances or other materials used in the production, from residues on equipment and from operators’ clothing shall be assessed. 6. Measures to prevent cross-contamination identified on the basis of quality risk management principles shall be put in place. Measures that may be considered to prevent cross-contamination include: (a) the dedication of a whole manufacturing site or a self-contained production area on a campaign basis (separation in time) followed by a cleaning process of validated effectiveness; (b) the use of segregated areas; (c) the use of closed systems for processing and for material or product transfer; (d) the use of airlocks and pressure cascade to confine potential airborne contaminants within a specified area; (e) the use of physical barrier systems, including isolators, as containment measures; (f) the dedication of specific equipment or certain parts thereof (e.g. filters) to a given type of product with a specific risk profile; (g) the utilisation of single use disposable technologies; (h) the implementation of validated cleaning or decontamination procedures adapted to the specific characteristics of the product and of the manufacturing process. The cleaning or decontamination procedures that are necessary, including the frequency thereof, shall be determined on the basis of a risk-assessment; (i) other suitable organisational measures, such as keeping specific protective clothing inside areas where products at high-risk of contamination are processed, implementing adequate measures for the handling of waste, contaminated rinsing water and soiled gowning, or imposing restrictions on the movement of personnel. 7. The control strategy shall address all the potential risks, including measures at the level of the premises, equipment and personnel, controls on materials used in the manufacture, implementation of effective sterilisation and sanitisations procedures, and adequate monitoring systems. The totality of the measures applied shall ensure the absence of contamination of the products manufactured within the manufacturing site. Sole reliance shall not be placed on any terminal process or finished product test. 8. The effectiveness of the measures implemented shall be reviewed periodically according to set procedures. This assessment shall lead to the implementation of corrective and preventive actions where necessary.