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12. GLOSSARY
Definitions of terms relating to qualification and validation which are not given in other
sections of the current EudraLex, Volume 4, are given below.
Bracketing approach. A science and risk based validation approach such that only
batches on the extremes of certain predetermined and justified design factors, e.g.
strength, batch size and/or pack size, are tested during process validation. The design
assumes that validation of any intermediate levels is represented by validation of the
extremes. Where a range of strengths is to be validated, bracketing could be applicable if
the strengths are identical or very closely related in composition, e.g. for a tablet range
made with different compression weights of a similar basic granulation or a capsule
range made by filling different plug fill weights of the same basic composition into
different size capsule shells. Bracketing can be applied to different container sizes or
different fills in the same container closure system.
Change Control. A formal system by which qualified representatives of appropriate
disciplines review proposed or actual changes that might affect the validated status of
facilities, systems, equipment or processes. The intent is to determine the need for action
to ensure and document that the system is maintained in a validated state.
Cleaning Validation. Cleaning validation is documented evidence that an approved
cleaning procedure will reproducibly remove the previous product or cleaning agents
used in the equipment below the scientifically set maximum allowable carryover level.
Cleaning verification. The gathering of evidence through chemical analysis after each
batch/campaign to show that the residues of the previous product or cleaning agents have
been reduced below the scientifically set maximum allowable carryover level.
Concurrent Validation. Validation carried out in exceptional circumstances, justified on
the basis of significant patient benefit, where the validation protocol is executed
concurrently with commercialisation of the validation batches.
Continuous process verification. An alternative approach to process validation in which
manufacturing process performance is continuously monitored and evaluated. (ICH Q8)
Control Strategy. A planned set of controls derived from current product and process
understanding that ensures process performance and product quality. The controls can
include parameters and attributes related to drug substance and drug product materials
and components, facility and equipment operating conditions, in-process controls,
finished product specifications and the associated methods and frequency of monitoring
and control. (ICH Q10)
Critical process parameter (CPP). A process parameter whose variability has an
impact on a critical quality attribute and therefore should be monitored or controlled to
ensure the process produces the desired quality. (ICH Q8)
Critical quality attribute (CQA). A physical, chemical, biological or microbiological
property or characteristic that should be within an approved limit, range or distribution to
ensure the desired product quality. (ICH Q8)
Design qualification (DQ). The documented verification that the proposed design of the
facilities, systems and equipment is suitable for the intended purpose.
Design Space. The multidimensional combination and interaction of input variables, e.g.
material attributes, and process parameters that have been demonstrated to provide
assurance of quality. Working within the design space is not considered as a change.