5. PROCESS EQUIPMENT

5. PROCESS EQUIPMENT
5.1 Design and Construction
5.10 Equipment used in the manufacture of intermediates and APIs should be of appropriate design and adequate size, and suitably located for its intended use, cleaning, sanitization (where appropriate), and maintenance.
5.11 Equipment should be constructed so that surfaces that contact raw materials, intermediates, or APIs do not alter the quality of the intermediates and APIs beyond the official or other established specifications.
5.12 Production equipment should only be used within its qualified operating range.
5.13 Major equipment (e.g., reactors, storage containers) and permanently installed processing lines used during the production of an intermediate or API should be appropriately identified.
5.14 Any substances associated with the operation of equipment, such as lubricants, heating fluids or coolants, should not contact intermediates or APIs so as to alter their quality beyond the official or other established specifications. Any deviations from this should be evaluated to ensure that there are no detrimental effects upon the fitness for purpose of the material. Wherever possible, food grade lubricants and oils should be used.
5.15 Closed or contained equipment should be used whenever appropriate. Where open equipment is used, or equipment is opened, appropriate precautions should be taken to minimize the risk of contamination.
Good Manufacturing Practice Guide for Active Pharmaceutical Ingredients
5.16 A set of current drawings should be maintained for equipment and critical installations (e.g., instrumentation and utility systems).
5.2 Equipment Maintenance and Cleaning
5.20 Schedules and procedures (including assignment of responsibility) should be established for the preventative maintenance of equipment.
5.21 Written procedures should be established for cleaning of equipment and its subsequent release for use in the manufacture of intermediates and APIs. Cleaning procedures should contain sufficient details to enable operators to clean each type of equipment in a reproducible and effective manner. These procedures should include:
− Assignment of responsibility for cleaning of equipment;
− Cleaning schedules, including, where appropriate, sanitizing schedules;
− A complete description of the methods and materials, including dilution of cleaning agents used to clean equipment;
− When appropriate, instructions for disassembling and reassembling each article of equipment to ensure proper cleaning;
− Instructions for the removal or obliteration of previous batch identification;
− Instructions for the protection of clean equipment from contamination prior to use;
− Inspection of equipment for cleanliness immediately before use, if practical; and
− Establishing the maximum time that may elapse between the completion of processing and equipment cleaning, when appropriate.
5.22 Equipment and utensils should be cleaned, stored, and, where appropriate, sanitized or sterilized to prevent contamination or carry-over of a material that would alter the quality of the intermediate or API beyond the official or other established specifications.
5.23 Where equipment is assigned to continuous production or campaign production of successive batches of the same intermediate or API, equipment should be cleaned at appropriate intervals to prevent build-up and carry-over of contaminants (e.g. degradants or objectionable levels of micro-organisms).
5.24 Non-dedicated equipment should be cleaned between production of different materials to prevent cross-contamination.
5.25 Acceptance criteria for residues and the choice of cleaning procedures and cleaning agents should be defined and justified.
5.26 Equipment should be identified as to its contents and its cleanliness status by appropriate means.
Good Manufacturing Practice Guide for Active Pharmaceutical Ingredients
5.3 Calibration
5.30 Control, weighing, measuring, monitoring and test equipment that is critical for assuring the quality of intermediates or APIs should be calibrated according to written procedures and an established schedule.
5.31 Equipment calibrations should be performed using standards traceable to certified standards, if existing.
5.32 Records of these calibrations should be maintained.
5.33 The current calibration status of critical equipment should be known and verifiable.
5.34 Instruments that do not meet calibration criteria should not be used.
5.35 Deviations from approved standards of calibration on critical instruments should be investigated to determine if these could have had an impact on the quality of the intermediate(s) or API(s) manufactured using this equipment since the last successful calibration.
5.4 Computerized Systems
5.40 GMP related computerized systems should be validated. The depth and scope of validation depends on the diversity, complexity and criticality of the computerized application.
5.41 Appropriate installation qualification and operational qualification should demonstrate the suitability of computer hardware and software to perform assigned tasks.
5.42 Commercially available software that has been qualified does not require the same level of testing. If an existing system was not validated at time of installation, a retrospective validation could be conducted if appropriate documentation is available.
5.43 Computerized systems should have sufficient controls to prevent unauthorized access or changes to data. There should be controls to prevent omissions in data (e.g. system turned off and data not captured). There should be a record of any data change made, the previous entry, who made the change, and when the change was made.
5.44 Written procedures should be available for the operation and maintenance of computerized systems.
5.45 Where critical data are being entered manually, there should be an additional check on the accuracy of the entry. This can be done by a second operator or by the system itself.
5.46 Incidents related to computerized systems that could affect the quality of intermediates or APIs or the reliability of records or test results should be recorded and investigated.
5.47 Changes to the computerized system should be made according to a change procedure and should be formally authorized, documented and tested. Records should be kept of all changes, including modifications and enhancements made to the hardware, software and any other critical component of the system. These records should demonstrate that the system is maintained in a validated state.
5.48 If system breakdowns or failures would result in the permanent loss of records, a back-up system should be provided. A means of ensuring data protection should be established for all computerized systems.
Good Manufacturing Practice Guide for Active Pharmaceutical Ingredients
5.49 Data can be recorded by a second means in addition to the computer system.