(1993; 36 pages)
6.1 Standard operating procedures shall be available and maintained up to date for all manufacturing operations.
6.2 Specifications for starting materials should include details of their source, origin and method of manufacture and of the controls applied, in particular microbiological controls, to ensure their suitability for use. Release of a finished product is conditional on satisfactory results being obtained in the tests on starting materials.
6.3 Media and cultures shall be added to fermenters and other vessels under carefully controlled conditions to avoid contamination. Care shall be taken to ensure that vessels are correctly connected when cultures are added.
6.4 If possible, media should be sterilized in situ. In-line sterilizing filters for routine addition of gases, media, acids, alkalis, defoaming agents, etc. to fermenters should be used where possible.
6.5 Careful consideration should be given to the validation of sterilization methods.
6.6 When an inactivation process is performed during manufacture, measures should be taken to avoid the risk of cross-contamination between treated and untreated products.
6.7 A wide variety of equipment is used for chromatography; in general such equipment should be dedicated to the purification of one product and should be sterilized or sanitized between batches. Problems of decontamination and purification may arise through repeated use of the same equipment at the same or different stages of processing. The life span of columns and the sterilization method shall be defined. Particular care should be given to monitoring microbial loads and endotoxins.