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The following message was posted to: PharmPK
I am curious as to the viewpoint of the bioanalytical people on this
discussion group on this topic. Here is the scenario:
A tox (or clinical) study is conducted before the bioanalytical method
is validated. The method is validated after the collection of the
samples. The samples are analyzed but will the bioanalytical group
release the data to the sponsor:
a) As soon as the samples have been analyzed and the data subjected to
QA review?
b) After the analysis of the samples (and QA review of the data) but
not until the long term storage data has been generated to support the
release of the data?
Regards
Mark Milton
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Hi Mark,
In the past here we have been able to provide the QC reviewed data to
the sponsor with the stability data pending. This is risk that sometimes
has to be taken. The main problem, as you can imagine, is if the
"stability samples" are not stable for enough time to cover the time
that the study samples remained in storage and possible delays by the
regulatory authorities (FDA) in making the final call on the study only
when the stability data has been generated.
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The following message was posted to: PharmPK
Mark:
If samples are collected before validation is complete, it is best to
store the samples and wait until validation is complete before analysis
is run. However, if the analysis has already been run prior to
completing validation, then it is subject to QA review. The crux is
define "complete validation". Typically the validation is considered
complete and ready to analyze samples prior to analysis of LTFS samples.
The LTFS analysis can be amended in to the validation report, or the
report can be issued after the LTFS is complete. Depending on the
outcome of the LTFS, there may be a subsequent protocol deviation added
to the run if LTFS failed.
With regards to timing of release, the CRO should provide the Sponsor
with a preliminary set of data (not QA'd) as soon as it is available.
This is useful for the Sponsor in determining if any re-assays need to
be done. QA should not be done until the run is complete, including
re-assays.
Hope this helps,
Mary
Mary M Sherman, Ph.D.
Aptuit Consulting, Inc.
Email: Mary.Sherman.at.aptuit.com
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The following message was posted to: PharmPK
Dear Mark,
As mentioned by other experts in the forum, as a regular practice
Bioanalytical method vlaidation has to be completed before the analysis
of tox samples. Because in the toxicity study protocol or study plan the
reference to the method validation report has to be given. The results
of long term stability can be generated later and added as an amendment
to the report and sent to QA for review separately.
If you are getting the method validated from a CRO, they will share the
unaudited data with the sponsor ASAP.
If you are analysing the samples before completing bioanalytical method
validation, then you are taking a calculated risk.
Regards
Dr. Tausif Ahmed
Metabolism and PK department
Ranbaxy Research Lab., India
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The risk is that the bioanalytical method may not fit the in life
application. For example if during validation, the material does not
pass freeze thaw or bench top stability, but the samples have already
been collected. Information revealed during validation will suggest how
the samples are to be collected- Do you add aprotinin or protease
inhibitor cocktail? Do you add an anti aggregation agent? If th3e
sample have already been collected, the addition of these components
will make the validation and sample analysis much more complicated.
From a regulatory standpoint, I believe you can get your Sponsor's and
your QA's approval to run samples before the validation report is
complete- using validation data tables but you need to get the method
validation report through your own QA and through the sponsors approval
before you RELEASE sample analysis reports.
--
Ed O'Connor, Ph.D.
Laboratory Director
Matrix BioAnalytical Laboratories
25 Science Park at Yale
New Haven, CT 06511
Web: www.matrixbioanalytical.com
Email: eoconnor.-at-.matrixbioanalytical.com
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Hi Mark
Even if your study is conducted before validating the method , but the
anaysis of the samples has been done after validation so the
validation will support your data .
But you need to take care for the Long term stability(LTS) data which
should cover entire days from the first sample collection time to end
of the last repeat sample analysis.
And even you can send the sample analysis data for the QA review
before LTS experiment.
LTS Report should be send as an addendum to the Validation report
which can be even submitted after the analysis of Study samples.
Regards
Nagesh
Sr.RA
BA Lab
NEKTAR India
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The following message was posted to: PharmPK
Hi,
My last two cents on this discussion. I think that unless the method
has
been tested extensively and the validation is just a matter of
formality, I would not touch the samples until the method has been fully
validated. In most cases, the samples are stable at -70C if stored
properly. If the drug is a generic one there may be stability data
available. Stability data generated by the lab will have to be submitted
as an amendment to the validation and the sample analysis report. So,
from my perspective, it is a greater risk to run the samples using a
non-validated method than to wait until the method has been validated.
Regards
Luis E. Sojo, PhD.
Associate Director Analytical Development
Bio-Analytical Unit
QLT Inc.
email:lsojo.at.qltinc.com
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The Long term storage data can be send as addendum and this has been
globally accepted. So the data can be sent to the sponsor as soon as
the samples have been analyzed and the data subjected to QA review.
There is no need to wait for the long term stability data.
Dr. Mandar Mote
Head Bio-analytical
CRO
Cadila Pharmaceuticals Ltd.
Ahmedabad.
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