Biomedical Engineering Reference
In-Depth Information
with, because it potentially impacted the quality attributes of
the product. Thus the criticality of the problem was
recognized from the start.
A deviation investigation team was formed including
responsible manufacturing, quality assurance, and laboratory
management and key personnel, and a project manager
was designated. This team initiated an investigation to
address the increase in data variability, beginning with a
comprehensive review of the product manufacturing process.
Their review focused on activities specifi cally infl uencing
drug potency. Activities reviewed included active drug
weighing and dispensing, active ingredient charging steps in
the manufacturing process, sources of process variation,
possible drug loss in processing, sampling of tablets for
potency testing, and analytical testing including all associated
procedures. The range of areas and activities included in the
investigation highlight the complexity of the problem.
A more specialized review team was formed in the
analytical area. This review team comprised the analytical
department manager, SMEs, laboratory analysts, and
associated personnel. This team reviewed all activities
associated with the drug potency assay, including standard
preparation, incoming sampling control, sample preparation,
high performance liquid chromatography (HPLC) instrument
control and operation, calculations, and other associated
activities. The accuracy of weighing the analytical standard
for the API was suspected as a potential contributing
factor to the increasing variation in drug potency.
Variability in weighing the analytical standard would in
turn cause variation in the potency determination of the
tablet product.
As part of its investigation (or perhaps “sub-investigation”),
this team conducted an experimental study of the accuracy
and precision of the balance used to weigh the analytical
