Chemistry Reference
In-Depth Information
for how each parameter was chosen. This section should also describe any system
suitability parameters established for the method (Chapter 5).
8.4.4 A
ccePtAnce
c
rIterIA
The acceptance criteria stipulate how the results will be evaluated. Because statisti-
cal evaluations are usually employed, clear instructions on the number of batches,
replicates, etc., are needed. It is common for simple statistics such as the mean and
standard deviation from repeated use of the method in the originating/transferring
laboratory to be used for acceptance criteria. More sophisticated statistics, such as the
F-test or t-test, are also commonly applied. The proper use of statistics can provide an
unbiased objective view of the comparison results of the transfer, and any approach
used should be a part of the overall protocol documentation. While a comprehen-
sive statistical discussion is outside the scope of this chapter, several good references
are available for more detail [13-15]. Because specifications are completely method,
instrument, sample, etc., dependent, hard and fast specifications are not listed in the
PhRMA guidance. However, a partial summary of the AAPS publications list of
recommended experimental design and acceptance criteria is presented in Table 8.2.
8.5 documentAtIon oF results: Amt report
Once completed, the results are summarized in an AMT Report. The report certifies
that the acceptance criteria were met, and that the receiving laboratories are fully
trained and qualified to run the method. In addition to summarizing all of the experi-
ments performed and the results obtained, it should also list all of the instrumenta-
tion used in the transfer. Similar to any laboratory exercise, an important aspect of
the AMT report is observations made while performing the method and should also
be included. Observations in the form of feedback can be used to further optimize
a method or to address special concerns that might not have been anticipated by the
originating laboratory.
Of course, sometimes the receiving laboratory may not meet the acceptance criteria
in the AMT protocol. When this situation arises, they should be addressed by a policy
that dictates how the situation should be handled. An investigation should be initiated
and documented in the summary report, and any corrective action taken justified.
8.6 potentIAl Amt pItFAlls
Many of the common pitfalls encountered during AMT can be prevented with a little
up-front work. It cannot be stressed enough that the robustness studies performed
during late method development or early method validation play a critical role in
the success of AMT. During robustness studies, the critical method parameters have
been identified and noted as a precautionary statement in the method. Intermediate
precision validation studies also can serve to identify potential AMT issues. By
anticipating that, for example, instruments, experience and training, and procedure
interpretations can all differ from laboratory to laboratory, many of the common
pitfalls can be avoided.
