PROCESS LIFECYCLE VALIDATION - Risk Management Applications in Pharmaceutical and Biopharmaceutical Manufacturing - page 214

TABLE 8.10 Severity, Occurrence, and Detection Rating for Cleaning Studies
Extreme Risk Rating Severity Occurrence Detection

10 Extremely

high, cause
harm to the
patient

Very high,
failure
almost
inevitable

No detection,
defect caused
by failure is
not
detectable

7 High High Significant risk

of no
detection

5 Moderate,

customer
experiences
some dis-
satisfaction

Moderate,
e.g., once
a month

Probable
detection,
process is
monitored
with
manually
inspection

3 Minor Low Very high

chance of
detection

1 None, no

effect

Remote,
almost
never

Almost certain
to detect,
defect is
obvious and
can be kept
from
affecting the
customer, all
units are
automatically
inspected

No Risk

TABLE 8.11 Determining Number of Hold Time Experiments or Extent of
Sampling Using RPN
RPN

Number of Experiments (Extent or Sampling Required)

<

125 0-1 (minimal or none)

125-150 1-2 (confirmation or moderate)

> 150 > 3 (multiples or extensive)

thresholds were established to determine the experimentation needed to justify
dirty hold times (Table 8.11).
The following risk factors should be considered for establishing the DEHT:

1. Drying on product surface: Certain organic compounds, APIs, waxes, or
polymeric formulations may harden or dry on standing, making them more