1. Determination of Quality Attributes
In performing the validation, defining the quality attributes—that is, gaining a clear understanding of the required quality and intended use—is the most important issue, and should be determined before starting the validation. Without defining required quality attributes we cannot establish validation protocols, which are the basis of all validation studies.
2. The Validation Protocol
A validation protocol is defined as
"A written plan stating how validation will be conducted and defining acceptance criteria. For example, the protocol for a manufacturing process identifies process equipment, critical process parameters/operation ranges, product characteristics, sampling, and test data to be collected, number of validation runs, and acceptable test results."
The validation protocol is a detailed plan for conducting a validation study. It is drafted by the individual or task group responsible for the project, reviewed for content and completeness following the firm’s protocol review procedure, and approved by designated individuals. It describes the responsibilities of each individual or unit involved in the project.
All protocols, whether for IQ (installation qualification)/OQ (operational qualification) of new equipment or for validating a new process, have the same basic format.
They start with an objective section, which describes the reasons for conducting the validation study as well as the results to be achieved. Next there is a scope section. Here what is to be included and excluded from the study is specified, effectively establishing the boundaries for the study. Following the objective and scope sections is a detailed description of the process/equipment to be validated. Here block diagrams of equipment, batch formula and master manufacturing records, process flow diagrams, and other documents that will help with the descriptive process are essential and should be attached to the protocol. The protocol should contain a detailed description of the sampling and testing schedule and procedures and clearly state the acceptance criteria for each stage of validation, such as DQ (design qualification), IQ, OQ, and PQ (performance qualification). The number of times that specific trials will be replaced in order to demonstrate reproducibility of results must be specified.
The protocol should be endorsed by designated representatives of each unit that will participate in the validation study. This is an essential step for validation study. It should be described that the protocol is accepted by responsible persons, and that each unit understands and agrees to fulfill its responsibilities as stated in the protocol. Subsequent changes to the protocol, should they be necessary, must be endorsed by the same individuals. Protocol addenda are sometimes necessary because circumstances later arise that were impossible to anticipate when the study was planned and the protocol drafted. In addition to approvals, the validation protocol should have the appended data sheets, which are to be filled with data obtained from the validation studies and compared with the criteria.
3. Steps of Validation