RISK-BASED CHANGE CONTROL - Risk Management Applications in Pharmaceutical and Biopharmaceutical Manufacturing - page 376

13.7.3.3 Calculated Risk The calculated risk was considered to be medium for
product mixing and heating scale-up, primarily because the existing controls for
this complicated process did not require a detailed mixing design analysis before
purchasing the equipment. The risk of using the wrong materials of construction
was considered low because existing controls are sufficient (Table 13.7). (Note
that detection is low, because detectability was high.)
13.7.3.4 Recommended Actions The following recommendation was devel-
oped to assure that quality is maintained during this change:
• Perform a detailed 3D engineering study before designing and purchasing
the new vessel. (The standard best practices analysis was not considered
sufficient to mitigate the risk for this product, because the process was too
complex.)
13.7.4 Case Study #4: Resin Inhibitor (FTA)
13.7.4.1 Change Description Consider a change in the concentration of an
inhibitor used in a resin storage solution to prevent biological growth. The resin
is used in the manufacture of a pharmaceutical product. It is desirable for process
safety purposes to reduce the inhibitor concentration as low as possible.
FTA is a technique that can be used to evaluate the effect on patient safety
because of a change in the pharmaceutical manufacturing process. An FTA is
developed from the top-down. These fault trees are built using gates and events
(blocks). The two most commonly used gates in a fault tree are the AND and OR
gates. As a visualization example, consider the simple case described by the ref-
erenced FTA (Fig. 13.2). This example has been oversimplified for demonstration
purposes.
In this example, consider two events (or blocks) comprising a top event (or a
system).
A change in inhibitor concentration possibly affecting patient safety (A) can
lead to
• unacceptable biological growth (B) or
• chemically altering the resin (C).
If occurrence of either event (B or C) causes the top event (A) to occur, then
these events (blocks) are connected using an OR gate. If one of those events
such as unacceptable biological growth (B) requires two other events to occur,
such as
• inhibitor concentration too low allowing bacteria to grow (D); and
• bacteria present in sufficient concentration to grow (E).
Should they occur together causing the event above (B) to occur, they are
connected by an AND gate.