Maintenance and cleaning
Article 18
1. Manufacturers shall establish: (a) schedules and procedures, including assignment of responsibilities, for the maintenance of equipment used in manufacturing operations; (b) written procedures for cleaning of equipment and its subsequent release for use in the manufacture of active substances and intermediates thereof. 2. The cleaning procedures shall be sufficiently detailed to allow cleaning of each type of equipment in a reproducible and effective manner, and shall include the description of the following: (a) assignment of responsibilities for cleaning of equipment; (b) cleaning schedules, including, where appropriate, sanitising schedules; (c) the methods and materials, including dilution of cleaning agents used to clean equipment; (d) instructions for disassembling and reassembling each article of equipment to ensure proper cleaning, where appropriate; (e) instructions for the removal or obliteration of previous batch identification; (f) instructions for the protection of clean equipment from contamination prior to use; (g) inspection of equipment for cleanliness immediately before use, if practical; (h) the maximum time that may elapse between the completion of processing and equipment cleaning, where appropriate. 3. Equipment and utensils shall be cleaned, stored, and, where appropriate, sanitised or sterilised to prevent contamination or carry-over of a material that would alter the quality of the active substances or intermediates thereof beyond the established specifications of the active substances or intermediates thereof. 4. Where equipment is assigned to continuous production or campaign manufacture of successive batches of the same active substance or intermediate thereof, equipment shall be cleaned at appropriate intervals to prevent build-up and carry-over of contaminants. 5. Equipment which is not assigned to continuous production or campaign manufacture of successive batches of the same active substance or intermediate thereof shall be cleaned between production of different materials to prevent cross-contamination. 6. Acceptance criteria for residues and the choice of cleaning procedures and cleaning agents shall be defined and the reasons for choosing them shall be documented. 7. Equipment shall be identified as to its contents and its cleanliness status.