Biomedical Engineering Reference
In-Depth Information
Preliminary risk assessment - where is the risk?
(Hu)man
Machines
Measurement
Replace
HPLC with
GC / LC-
MS-MS
Enhance
skills for better
control of CPPs
SPC for (C)PPs
Production
Pareto charts
of yields
Train supervisor s
for oversight
duties
Analytical
Facility
Chart deviations
SPC for
reference
standard
Replace
column
Daily improvement
program
Safe & effective
meetsor exceeds
customer's
expectations
External expert(s)
provides new skills
Reduce particle
size to improve
mixing
Different
suppliers
Microbial
controls
Physical
Realign with
strategic goals
Active/API(s)
LOD/LOQ*
Review and
plan
Process
Different
batches
(C)PPs:
Time
Temp
Batch size
Other?
Providere
sources
Inactive-
excipients
Analytical
Granulation
*LOD/LOQ=Limit of detection/
quantitation - by increasing the
analytical capability obtain more
accurate measurement
Materials
Methods
Management
Figure 6.3
Ishikawa diagram for risk assessment. ( See insert for color representation of
the figure .)
the human engineering perspective will be considered and designed into the
process.
The Ishikawa diagram in Figure 6.3 provides an example of potential
hazards.
The diagram shows many items that are clearly potential risks. For example,
weighing could fail because personnel are careless about discarding single-use
scoops —or because they think they will save the company money and reuse the
same scoop—potentially contaminating another material. Therefore, the human
element should consider the possibility of cross contamination as a high risk and
allow for developing controls that might include a high level of training, testing,
and ongoing oversight and verification regarding personnel understanding of this
issue. Weighing could also fail because of a mix-up of materials, so process flow
and placement of items in the weighing area as well as labeling would all be
important control points under “machines” (facility layout) and “methods” but
would also need emphasis under “man” because once the controls are imple-
mented it is critical to their ongoing functioning that personnel understand why
they are there and how to implement them correctly.
Mixing can fail for numerous reasons, but if the particle size of the active
ingredient is substantially different from batch to batch, many (C)PPs might be
affected and the mixing will no longer be homogeneous. If purchasing under-
stands this is a critical control point, they will ensure that the specification is
incorporated into the quality contract with the API manufacturer, not merely as
one more bullet point but as a nonnegotiable, go/no go parameter and they might
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