(2003; 148 pages)
Prevention of cross-contamination and bacterial contamination during production
16.10 When dry materials and products are used in production, special precautions should be taken to prevent the generation and dissemination of dust. Provision should be made for proper air control (e.g. supply and extraction of air of suitable quality).
16.11 Contamination of a starting material or of a product by another material or product must be avoided. This risk of accidental cross-contamination arises from the uncontrolled release of dust, gases, particles, vapours, sprays or organisms from materials and products in process, from residues on equipment, from intruding insects, and from operators’ clothing, skin, etc. The significance of this risk varies with the type of contaminant and of the product being contaminated. Among the most hazardous contaminants are highly sensitizing materials, biological preparations such as living organisms, certain hormones, cytotoxic substances, and other highly active materials. Products in which contamination is likely to be most significant are those administered by injection or applied to open wounds and those given in large doses and/or over a long time.
16.12 Cross-contamination should be avoided by taking appropriate technical or organizational measures, for example:
(a) carrying out production in dedicated and self-contained areas (which may be required for products such as penicillins, live vaccines, live bacterial preparations and certain other biologicals);
(b) conducting campaign production (separation in time) followed by appropriate cleaning in accordance with a validated cleaning procedure;
(c) providing appropriately designed airlocks, pressure differentials, and air supply and extraction systems;
(d) minimizing the risk of contamination caused by recirculation or re-entry of untreated or insufficiently treated air;
(e) wearing protective clothing where products or materials are handled;
(f) using cleaning and decontamination procedures of known effectiveness;
(g) using a “closed system” in production;
(h) testing for residues;
(i) using cleanliness status labels on equipment.
16.13 Measures to prevent cross-contamination and their effectiveness should be checked periodically according to standard operating procedures.
16.14 Production areas where susceptible products are processed should undergo periodic environmental monitoring (e.g. for microbiological monitoring and particulate matter where appropriate).