RISK-BASED CHANGE CONTROL - Risk Management Applications in Pharmaceutical and Biopharmaceutical Manufacturing - page 374

assurance (data) that future batches will meet the product quality and compliance
requirements.
13.7.2 Case Study #2: Primary Component Change for a Sterile Product
13.7.2.1 Change Description Containers (glass vials) made by a particular
supplier are being replaced. Alternate containers meeting current material speci-
fications (dimensionally and chemically equivalent) are available from the other
supplier at a different facility.
13.7.2.2 Potentially Impacted CQAs Incoming bioburden/contamination
(existing cleaning and sterilization cycles are based on the now-discontinued
vials) is one CQA (specification) that could be adversely impacted by using a
different supplier.
Incoming bottle integrity (breaks or cracks can cause sterility failure) could
also be adversely impacted.
13.7.2.3 Calculated Risk The overall risk for the identified risk events
(Table 13.6) is generally high, primarily because the severity of a sterility failure
and the detection of an occasional sterility failure are always high. (In normal
(acceptable quality level) AQL testing, there is a low likelihood of detecting an
occasional sterility failure.)
13.7.2.4 Recommended Actions Actions recommended to mitigate the risk
include increasing incoming quality assurance (IQA) inspections, performing a
vendor audit/qualification, reexecuting cleaning and sterilization cycle validation,
and conducting at least one media fill run.
13.7.3 Case Study #3: Equipment Change
13.7.3.1 Change Description During the synthesis of a corrosive, temperature-
sensitive pharmaceutical suspended solid, a 350-liter jacketed mixing vessel is
used to heat and mix the suspension. It is being changed to a 700-liter vessel to
increase batch size.
13.7.3.2 Potentially Impacted Critical Quality Attributes The attributes consid-
ered critical to meeting product specifications (and thus ensuring patient safety)
were identified as follows:
• materials of construction (corrosion);
• mixing fluid dynamics (flow, shear, etc.); and
• temperature uniformity.
These characteristics and the integrity of the process need to be maintained in
the design of the new equipment.