RISK-BASED CHANGE CONTROL - Risk Management Applications in Pharmaceutical and Biopharmaceutical Manufacturing - page 366

There are many other types of systematic analysis tools that are used to mit-
igate risks during change control [1]. These techniques are typically associated
with hazard analysis [4]. These tools include, but are not limited to, the following:

• checklists;
• what-if analysis; and
• FTA (fault tree analysis).

A checklist method incorporates a list of qualitative, predefined system risks.
A checklist is particularly useful when the variables are known, such as regulatory
requirements. Checklists are routinely used as prescreening methods that identify
known variables to reduce the amount of review time for more rigorous methods,
such as FMEA.
In a “What-if” qualitative analysis, an individual and/or a team compiles a list
of what-if questions designed to test the system; for example, “what if the power
to a storage freezer is interrupted?” A potential consequence in this example
may be that the product stored within the freezer is compromised. Potential
safeguards (i.e., controls) may include high temperature alarms. The results of a
what-if analysis are presented in the form of a table that includes the questions,
potential consequences, safeguards in place, and recommendations.
The FMEA begins with the identification of a failure or a fault, whereas an
FTA begins with a top risk; then all possible causes are evaluated in the form of
a tree. The faults are quantified in accordance with each of their risks. The FTA
is a visual tool (refer to Fig. 13.2 for an FTA example).

Inhibitor concentration
change can affect
patient safety
A

OR

Unacceptable bacterial
growth
MODERATE
B

Chemically damage
resin
LOW
C

AND

Inhibitor concentration
allows bacteria to grow
HIGH
D

Bacteria present in
sufficient concentration
LOW
E

Figure 13.2 Resin inhibitor risk assessment (FTA).