Chemistry Reference
In-Depth Information
tAble 5.6
example Instrument sample Queue
sample
# of Injections
Blank (diluent)
At least 1
System suitability
5
Check std.
1
Working std.
1
Blank (diluent)
1
Sample prep 1
1
Sample prep 2
1
Sample prep 3
1
Sample prep 4
1
Sample prep 5
1
Sample prep 6
1
3.0 µg/mL Working std.
1
Blank (diluent)
1
5.9 metHod AdJustments to meet system
suItAbIlIty reQuIrements
Adjustments to USP methods have been allowed to satisfy system suitability require-
ments as often noted in individual monographs. Historically, as long as adjustments
to the method are made within the boundaries of any robustness studies performed,
no further actions are warranted. Any adjustment outside the bounds of the robust-
ness study constitutes a change to the method, requiring a revalidation. However,
many USP methods precede the adoption of robustness studies, or the results were
not available.
In 1998, Furman et al. proposed a way to classify allowable adjustments [19].
But it was not until 2005 that guidance appeared on the topic [20-22]. The FDA
Office of Regulatory Affairs (ORA) has had guidance in place for a number of
years [20], and after some deliberation the USP has also now included guidelines
into Chapter 621, Chromatography [17]. Table 5.7 summarizes the maximum adjust-
ments allowed for various LC and GC parameters taken from both the USP and
ORA documents. Adjustments outside the ranges listed in Table 5.7 constitute
modifications, or changes, which are subject to validation. Chromatographic adjust-
ments in order to comply with system suitability requirements should not be made
to compensate for column or system failure, and adjustments to the composition of
the mobile phase in gradient methods are not recommended. If adjustments to gradi-
ent methods are necessary, only column changes (same packing material) or dwell
volume adjustments are recommended. Adjustments should only be made from the
existing method as written as a starting point each time the method is run. Multiple
adjustments can have a cumulative effect on the performance of the system and
should be considered carefully before implementation.
