PROCESS LIFECYCLE VALIDATION - Risk Management Applications in Pharmaceutical and Biopharmaceutical Manufacturing - page 211

8.9.2 Defining a Periodic Review Schedule of Validated Process/Systems

When defining a review schedule of validated systems/process, a risk-based
approach could be used to rank the systems or classify them according to com-
mon features. For example, potential sources or factors influencing the schedule
could be as follows:

• criticality of the quality attribute being measured;
• deviations or past history of the system; and
• production volume or use of the system.

Four levels of severity and probability are defined in this example. Severity
would be a measure of the criticality or impact on the validated system. Table 8.9
shows that severity depends on four levels of control of CQAs and CPPs. Fre-
quency is based on percentage of batches with deviations and production volume,
also with four levels. Those systems that directly control or impact a CQA or CPP
would be the most severe, whereas monitoring a noncritical parameter would be
the least. If a system has frequent deviations ( > 2%) or use ( > 50 batches/year),
the system would have the highest frequency.
In this example, risk scores (i.e., Severity × Frequency) would range from 1
to 16 (Table 8.9). Predetermined thresholds of review periods could be ranked or
grouped into periods of time. A risk score was used to rank systems into three

TABLE 8.9 Definition of Severity and Probability for Review Scheduling of
Validated Systems
Ranking

Severity Probability or Frequency

1 Monitors a quality

attribute(s) that is
classified as noncritical

No deviations for 5 years and/or
low production volume (

≤

3

batches/yr)

2 Monitors critical quality

attributes

No deviations since last review
(2-5 years) and/or low
production volume (4-8
batches/yr)

3 Indirectly controls critical

process parameter/critical
quality attribute

Deviations 2% of the batches

produced since the last review
(2 years) and/or moderate
production volume (9-50
batches/yr)

≤

4 Directly controls critical

process parameter/critical
quality attribute

Deviations observed in > 2% of
the batches produced since the
last review (2 years) and/or
moderate production volume
( > 50 batches/yr)