Validation is an integral part of quality assurance, but the use of this term in connection with manufacturing often gives rise to difficulties. As defined above, it involves the systematic study of systems, facilities and processes aimed at determining whether they perform their intended functions adequately and consistently as specified. A validated operation is one which has been demonstrated to provide a high degree of assurance that uniform batches will be produced that meet the required specifications, and has therefore been formally approved.

Unlike many other requirements of GMP, validation in itself does not improve processes. It can only confirm (or not, as the case may be) that the process has been properly developed and is under control. Ideally, any development activity in the later stages should be finalized by a validation phase.¹ This includes, in particular, the manufacture of investigational products and the scaling up of processes from pilot plant to production unit. In this event, GMP as manufacturing practice may only be concerned with revalidation, e.g. when processes are transferred from development to production, after modifications are introduced (in starting materials, equipment, etc.) or when periodic revalidation is performed.

¹ It may be noted that in some countries data on process validation are required at the preregistration stage (in the submission of. or application for, marketing authorizations).

However, it cannot be assumed that all processes in the pharmaceutical industry worldwide have been properly validated at the development stage. Consequently, validation is discussed here in a broader context as an activity which is initiated in development and is continued until the stage of full-scale production is reached. In fact, it is in the course of development that critical processes, steps or unit operations are identified.

Good validation practice requires the close collaboration of departments such as those concerned with development, production, engineering, quality assurance and control. This is most important when processes go into routine full-scale production following pharmaceutical development and pilot-plant operations. With a view to facilitating subsequent validation and its assessment in the course of quality audits or regulatory inspections, it is recommended that all documentation reflecting such transfers be kept together in a separate file ("technology transfer document").

Adequate validation may be beneficial for the manufacturer in many ways:

• It deepens the understanding of processes, decreases the risks of processing problems, and thus assures the smooth running of the process.

• It decreases the risks of defect costs.

• It decreases the risks of regulatory non-compliance.

• A fully validated process may require less in-process control and end-product testing.