Chemistry Reference
In-Depth Information
of this new column technology [15]. Adjustments in this category are usually accom-
modated in an Annual Report, but some companies, acting conservatively, may use
a CBE or CBE-30 document. Actual determination of which document to file may
be part of a risk assessment, or an existing SOP. And again, as mentioned previ-
ously, the type of supplement is also dictated somewhat by the types of sample, for
example, drug product versus drug substance.
9.6 Implement An exIstIng stAndArd
metHod WItH cHAnges
When a new method is implemented in a regulated laboratory, it must be revalidated.
Validation is also required when the existing standard method is modified enough
to change it, and also a good idea when the existing method is applied to a sample
matrix significantly different from that for which the original method was intended.
There are many reasons to change a method, and changes to a method can be either
reactive or proactive. Reactive situations might exist if there were significant changes
to incoming raw material or the manufactured batch, or formulation changes. If it
becomes necessary to modify a method to satisfy system suitability requirements
so much that it becomes a change, it may also be necessary to perform an out-of-
specification (OOS) investigation [16,17].
Many laboratories are proactive with method changes, and implementing new
technology fits into this category. New columns, column chemistry, and other
method improvements occur frequently, and business case studies are undertaken to
determine what changes might be made as cost-cutting or time-saving options. With
new technologies resulting in analysis times as short as a minute, with improved
sensitivity and no loss in resolution, and software tools available to analyze the data
more quickly, revalidation time can be significantly reduced. Some will take the
course of action “if it ain't broke, don't fix it,” but many companies take advantage of
new technology because it makes sense from a business standpoint, even if it means
changing the method, investing additional time and resources, and doing a little
extra paperwork.
Changes themselves can be of different magnitudes and result in different
approaches for implementation. If the changes are so drastic that the applicant is
essentially establishing a new or alternative analytical procedure, a PAS is required
as this situation falls into the major change category. The same is true in the instance
where a change is being made to relax specifications.
However, when adopting, for example, new HPLC technology, analysts gener-
ally operate under the assumption that a change is always being made for the better;
that is, not relaxing specifications but providing an
increased
assurance of identity,
strength, purity, or potency of the material being tested. It can also be further argued
that adopting new LC technology is not equivalent to adopting an alternative pro-
cedure. A change in column chemistry or scale should not be rated the equivalent
of changing from an HPLC method to a titration method, or to NMR or IR, or vice
versa. So a change in this category might also be satisfied by either type of CBE doc-
ument. Of course, the standard method is the legal control procedure. Any change to
the procedure would require a CBE-30 submission.
