(1999; 168 pages) [Spanish]
7.2.1 Prevention of cross-contamination
Potential for cross-contamination should be considered in the design of the manufacturing process and facility. The degree to which cross-contamination should be minimized depends on the safety and intended use of the excipient.
The precautions taken to minimize cross-contamination should be appropriate to the conditions of the manufacturing facility and will take account of the range of materials manufactured. When the excipient product is initially recovered, it should be in a clean environment and not exposed to airborne contaminants, such as dust from other excipient or industrial chemicals. Typically, the damp product will be unloaded into clean, covered containers and transported for drying and other manipulations. These subsequent operations should be performed in separate areas or under controlled conditions because once dry, the excipient is more likely to contaminate its environment, including any surrounding products. The primary consideration is that the building and facilities should not contribute to an actual or potential contamination of the excipient.
The air handling systems at the site of manufacture should be designed to prevent cross-contamination. In dedicated areas processing the same excipient, it is permissible to recycle a portion of the exhaust air back into the same area. The adequacy of such a system of operation for multi-use areas, especially if several products are processed simultaneously, should be carefully analysed. In multi-use areas where several products are completely confined in closed vessels and piping systems, filtration of the supply air (combined fresh make-up air and recycled air) is acceptable if the conditions are consistent with other existing regulations (e.g. environmental, safety).
In those areas where the excipient is in a damp or moistened form, such as filter or centrifuge cake, and may be exposed to room air, filter efficiencies in the supply air system as low as 85% may be adequate. In those areas where one or more of the products is being processed in a dry form, such filtration may not be enough to prevent cross-contamination. In all cases, manufacturers should be able to demonstrate the adequacy of their air handling systems.
Excipient manufacturers should have a documented programme identifying all insecticides, pesticides, rodenticides and herbicides used at the site of manufacture. Adequate measures should be taken to prevent these agents contaminating the excipients.