(1999; 168 pages) [Spanish]
7.1 Change control and process validation
Process changes may lead to changes in inherent product characteristics. Manufacturers should have a formal process change system in place, with written standard operating procedures covering such changes. Management of the change system should be assigned to an independent quality unit having responsibility and authority for final approval of process changes.
Manufacturers of excipients often produce laboratory or pilot batches. Scale-up to commercial production may involve several stages and data should be reviewed to demonstrate the adequacy of the scale-up process. Scale-up may introduce significant problems of consistency between batches. Pilot batches should serve as the basis for establishing in-process and finished product purity specifications.
Typically, manufacturers will generate reports that discuss the development and limitation of the manufacturing process. Summaries of such reports should be reviewed to determine if the plant is capable of producing the excipient. The reports serve as the basis for the validation of the manufacturing and control procedures, as well as the basic documentation to demonstrate that the process works consistently.
A document comprising scale-up data and describing the process reactions, operating parameters, purifications, impurities and key tests needed for process control should be written. A retrospective analysis of historical data (through statistical data and process capability data analysis) as well as the previous documentation will provide a good basis for validation.