POINTS TO CONSIDER FOR COMMISSIONING AND QUALIFICATION OF MANUFACTURING FACILITIES AND EQUIPMENT - Risk Management Applications in Pharmaceutical and Biopharmaceutical Manufacturing - page 162

the relative risk of the occurrence, than discussion over what the risk “number”
should be.
While these examples are purely hypothetical and do not represent specific
manufacturing situations, they present descriptions that are not uncommon in the
industry and could indicate potential ranking determination considerations.
7.3.11 Test Function and Acceptance Criteria
Qualification test functions should be developed to demonstrate the capability of
equipment as it relates to process performance and product quality. It may not
be necessary to test equipment and systems capability beyond the range expected
during the process. However, the tests should be based on sound scientific and
engineering criteria and match with those functions that affect product quality.
The FDA process validation guidance suggests that qualification of utilities
and equipment verify that the utility system and equipment operate in accor-
dance with the process requirements in all anticipated operating ranges [15].
This should include challenging the equipment or system functions while under
load comparable to that expected during routine production.
The acceptance criteria should be useful, attainable, and verifiable. Useful
means that the criteria represent a challenge to the system. It should not be so
easily obtained that it does not provide confidence of the continued reliability
of the system operation. An example might be qualifying a clean room, which
must meet Class 100 or less than 100 particles of 0.5 microns or larger per cubic
foot per minute sample. Modern, well-designed clean rooms should be able to
perform below the 100 limit. Setting criteria at 100 may be technically correct,
but may not provide an indication if the system is performing properly.
Attainable means that the criteria are not beyond the range of performance
and therefore too difficult to obtain. An example might be setting automated
inspection machine qualification limits at zero. This certainly is the optimal per-
formance level, but obtaining zero may not be realistic using current technology
or may result in unacceptable levels of “false” defects rejected. A more real-
istic level of defect rejection, above zero, may be attainable and represent an
acceptable risk level to patient safety.
Verifiable means that the criteria can be quantified or objectively confirmed. An
example of unverifiable criteria might be requiring that the fill line run well or the
vessel be “free of foreign material residue.” These terms lack quantifiable limits.
They would be subjective, open to interpretation, and difficult to prove. Likewise,
setting criteria that all product transfer line surfaces be visually inspected and
shown to be free-of-pitting might be an acceptable criteria, but the test function
might be impossible to perform. In this case, the test function to satisfy the free-
of-pitting criterion might be a confirmation of material of construction combined
with an inspection of a representative sampling of surfaces.
Risk to patient safety and product quality should be considered in determining
the test function and acceptance criteria. Let us say the transfer lines will carry
a relatively noncorrosive material, which will go through further downstream