Biomedical Engineering Reference
In-Depth Information
during routine operations, usually the range found in
manufacturing instructions. It takes into account
minimum and maximum values tested during initial
development and a review of process history, which
shows the capability of operators, facility, equipment,
and utilities. The proven acceptable range is defi ned by
minimum and maximum values for each parameter
found during the range-fi nding studies. Range-fi nding
studies are often designed such that the ranges
studied are two or three times the normal operating
range. If a parameter's operating range is less than
two times its acceptable range, i.e. r
o
< 2
x
r
a
, this
indicates that a deviation to the normal operating
range would likely result in a failure to meet an
in-process control, in-process specifi cation, or failure of
the batch.
16. ICH (2005) op. cit. As Kevin O'Donnell and Anne
Greene (2006) have expressed it:
risk events can have multiple causes, with multiple
associated risks, some less important that [
sic
]
others. This can result in formal risk management
activities becoming costly and quite labor-intensive
exercises, and should, therefore, be targeted at the
most
complex
or
critical
issues” (italics added).
17. 21 CFR 211.192, “Production Record Review.” See
also Gamal Amer (2008) on the “two types of quality
events associated with risk.”
18. See ICH (2008).
19. A similar critical review of the weighing SOP itself was
required, but not included here. In addition, that review
took into account the guidance provided by
US
Pharmacopeia
<1251>.
