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Dear All We conducted Incurred sample reanalysis (ISR) for
Atorvastatin in human plasma, out of 56 samples that we analysed 2
sample were showing nearly 39% change when comapred with the original
values, for remaining all the samples the %change was below 15%. 1)Now
what to do whether it should lead to investigation ( what are all the
parameters that should we investigate) 2) as more than 67% sample
were with in limits is it accetable as per current regulatory bodies
thinking 3)Do we need to anything else Your inputs are required
Thanks in Advance With RegardsDev
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Regulatory guideline says more than 67 % should be within 15 % , so
these failing samples need not be considered for calculation. You
don't need to include any investigation report, but it is a good
practice to investigate the cause of failure and document it. Some of
parameters to look at is bad IS addition, sample spillage during
extraction, wrong integration, wrong/missed injection.
Regards,
Vinayak
Vinayak Nadiger
Manager , Bioanalytical Chemistry
11 Biopolis Way, Helios #08-05
Singapore 138667
E Mail: vnadiger.at.combinatorx.com
Website:www.combinatorx.com
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I would agree with Vinyak.
-Tom
Thomas L. Tarnowski, Ph.D.
Bioanalytical Development
Elan Pharmaceuticals, Inc.
800 Gateway Boulevard
South San Francisco, CA 94080
thomas.tarnowski.-a-.elan.com
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Dear Mr. Vinayak Nadiger,
I am not aware that the regulatory agemcies have put down some
concrete guidelines regarding Incurred sample reanalysis. If you have
come across these guidelines, kindly let me know if possible.
Warm regards,
Noel Gomes,
Accutest Research Laboratories,
Navi Mumbai.
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I agree that there was a white paper on Incurred sample reanalysis put
in this year. But there are no concrete guidelines set up till date by
the FDA or any other regulatory stating the acceptance criteria. We
have done ISRA of in excess of twenty to twenty-five molecules with
acceptable precision and accuracy. However the limits to be set up are
solely upto us , at the given pont of time. Maybe the FDA will come
out with some guidelines on the same in time to come. Also given the
present situaution, two samples going out of accepatance would not
ring alarm bells for me.
Warm regards,
Noel Gomes,
Accutest Research Laboratories,
Navi Mumbai.
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Hello Devender
My two paise...
1) You should investigate, was duplicate aliquot good enough, any
temperature variation during storage / transit, processing error,
integration error etc. If you still have the sample, go for a repeat.
2) Data acceptable / submitable or not, depends upon your predefined
SOP or protocol.
3) Document adequately
Cheers!
Himanshu
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The following message was posted to: PharmPK
Dear devender
In your ISR expt since out of 56 samples analysed only 2
samples failed and were not within acceptance criteria (i.e % change is
nearly 39%), it seems that it doesn't have much impact from regulatory
considerations (as more than 67%samples were within acceptance
criteria).
In addition to this if you want to perform ISR for failed samples (on
safer
Side) proceed as per your in house procedure. Draft a failure
investigation
Report & investigate for the following reasons like, which may or may
not be limited to.
1) Poor chromatography
2) Variation in Internal STD response
3) Instrumental malfunctions which include
i) High back pressure in chromatographic device.
ii) Leakage in column compartment of HPLC.
iii) Stoppage of analytical run in between due to software
miscommunications.
iv) Other problems like irregular response due to gas fluctuations in
between runs (mass spectrometric related) and injection not taken due to
some acquisition error.
Hope these inputs may help you & related to your query to certain
extent.
Comments for this reply from pharmPK members are welcome.
with regards
manoj Krishnan
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The following message was posted to: PharmPK
A bad IS,sample spillage, missed injection, poor integration, would
lead to
rejection of the repeat. There is actually no result for the second
attempt
and it should be re-analyzed. An SOP should describe the reasons for
repeat
and should require repeat for the reasons listed above.
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The following message was posted to: PharmPK
Vinayak: The first pass is the that assay is acceptable. The second
pass
is the the response of the sample must be acceptable. If the sample
response fails to meet acceptance criteria because of response issues-
internal standard response, analyte response out of tolerance, poor
integration, poor peak shape, CV issues for ligand binding or if
processing
issues are known and recorded (spillage-missed injection), then you
have no
second response and the analysis needs to be repeated.
I do not believe that a 15% tolerance is written anywhere for repeat
analysis.
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