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I would like to clarify with the group that we did developed an
analytical method and confirmed with selectivity, recovery, matrix
effect and 3 PA batches for a drug. But on the day 1 of the validation
PA batch was failed and the response of analyte was very less compare
to the developmental PA batches. The wrong thing in the process was we
did calibrated MS/MS detector. We decided to relook in to the method
(column and MS/MS parameters), so terminated the validation procedure.
My question here is, do we need to investigate the reason for the
failure and document it before going for validation with changed
conditions. Do the regulatory agencies ask for the investigation and
documentation of the failure. My opinion is, since it is in the method
validation stage; we need not to document the failure reasons & after
completion of the validation we can handover the validated data for QA
What is the role of QA in method development and method validation
procedures up till the method validation is completed.
I request comments from experts in regulatory view.
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I think if validated method was handed to the concerned and it did not
work accordingly and asked to re-validate the method. then the
appears and solution of these problems should also be documented and
handed to the concerned. On the hand, it is better to document but not
necessary to hand over.
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Regarding a validation that was aborted in the first run because of
recognized issues; and then conditions and parameters were adjusted,
and the validation was started from the beginning again, my opinion is
that you need to document in the study record (notebook or study
binder) why the first validation failed and what you changed. This
needs to be clear enough so that you or someone else could reconstruct
the process some if needed some time in the future, but it may not
need to be much longer than the email you sent. You should have a
validation protocol for the validation, so it will need to be revised
in some way for the second validation to note any changed parameters.
QA is not mentioned in the US FDA 2001 guidance on Bioanalytcal Method
Validation, and there is no regulatory requirement for their
participation. However you should have SOPs in place in your lab,
including one on how validations are conducted, so you need to follow
your SOPs. Therefore, if a QA role is defined in your SOPs, then
follow your SOPs. There is a lot of variation in the industry on QA
participation in validations. Many find an independent review of the
process and data helpful, and others do without QA participation.
Thomas L. Tarnowski, Ph.D.
Elan Pharmaceuticals, Inc.
800 Gateway Boulevard
South San Francisco, CA 94080
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