PROCESS LIFECYCLE VALIDATION - Risk Management Applications in Pharmaceutical and Biopharmaceutical Manufacturing - page 192

8.7.3 Example 1: Defining Controls for Tablet Compression/Coating Process

In this example, risk scoring is used to select controls for tablet compres-
sion/coating process. In the beginning, scales for severity, frequency of parameter
being out of range, and action thresholds are defined (Tables 8.5 and 8.6).

8.7.3.1 Determination of Overall Risk The overall risk is determined by a risk
index (RI). The RI is calculated as follows: RI = Severity (S) Frequency (F).

Using the risk scoring described, an RI threshold was established to classify a
parameter as a CPP (Table 8.6).
Thresholds for action (or for determining criticality) based on risk scoring
should be agreed on by reviewers before performing RA. An example of action
thresholds based on this scoring strategy is shown here. Justification of val-
ues assigned to severity and frequency for each evaluated risk should be pro-
vided in the RA documentation. Table 8.7 shows an example of the output of
the RA.

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TABLE 8.5 Four Level Scales of Severity and Frequency for a Process Parameter
Severity ( S ) Definition Interpretation

8 High Predicted to cause severe impact to

quality

4 Moderate Predicted to cause significant impact

to quality

2 Low Predicted to cause minor impact on

quality

1 None Predicted to have no impact on

quality of product

Frequency ( F )or
Probability of
Occurrence Definition Interpretation

10 High Problem likely to occur frequently

(expected or has occurred multiple
times in the past)

7 Moderate Problem has occurred in the past and

can be expected to reoccur if action
is not taken to correct or prevent

3 Low Problem unlikely to occur but is

possible

1 Remote Highly unlikely to occur (probability

of failure occurring is so low that
it can be assumed that the failure
will not reoccur)