One question asked frequently is: What is the leading specification?
This issue comes up at different stages in a product's life cycle, causing repeated discussions and requiring no small amount of time for a variety of personnel functions in a GMP system. The question is especially prevelant when summarizing certain phases of the product life cycle in the form of summary reports or when using specifications as a prerequisite for GMP processes such as qualification of equipment and validation of processes. Classic examples are summary lists of specifications from the development of manufacturing processes, from the transfer of development to production or from production itself, including the associated change history.
However, lists such as overviews of parameters and specifications within the scope of manufacturing notifications to the competent authorities or other descriptions of manufacturing processes, e.g. in the form of flow charts, are usually also available.
The background to the question of the leading specification is the uncertainty or lack of clarity as to which function and which update status the respective specification lists have should they at least partially describe the same parameters.
In the case of process validations or re-validations, at a minimum, the specifications officially reported as part of the manufacturing process description are binding. This means that the validation must show that the process functions in a reproducible and controlled manner and consequently also meet the specifications belonging to the "reported" process control.
If a manufacturer, in order to additionally increase the security of the control, internally maintains narrower specifications for his process parameters than the specifications reported to the authority, compliance with the narrower specifications shall be checked with regard to the (re)validation.
Asking for the leading specification becomes even more complex if the same product is produced at different sites of the same company and if there are differing specifications.
In such cases, "global" decisions may have to taken to determine the degree of consistency or harmonization of specifications.
In any case, a clear functional description and a visualization of the hierarchy and dependencies of the specification lists, including the integration of these descriptions into the GMP system via the drafting of an SOP, will help in selecting the right specification for the task at hand.