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Dear Group,
Requesting the group members to have their general consensus and put =20
their comments on the requirement to perform Stock solution =20
verification test after preparing two separate stocks for Calibration =20
standards (CC) and Quality control (QC) samples. As per US FDA =20
guidelines, it is not manadatory to prepare Standards and QC samples =20
from two different stock solutions provided stock solution stability =20
and accuracy have been verified.
I would appreciate for all the comments on whether it is alright if
1) we are preparing two different stocks separately for CC and QC by =20
two different analysts and checking the solution accuracy (within =B1 =20
15% of Nominal) of the QCs at LQC, MQC and HQC levels prepared from =20
second stock against the linearity standard plot from the first stock.
2) we are preparing two different stocks separately for CC and QC by =20
the same analysts and checking the solution accuracy (within =B1 15% of =20=
Nominal) of the QCs at LQC, MQC and HQC levels prepared from second =20
stock against the linearity standard plot from the first stock.
3) we are preparing only one stock solution and CC prepared by one =20
analyst and QC prepared by another analyst and then verifying for the =20
accuracy of the above mentioned QCs against the CC.
Now in either of the above situations, if the CC standards and QC =20
samples meet the SOP acceptance criteria of =B1 15% of Nominal, in my =20
opinion, we can proceed with further spiking and analysis. My only =20
concern is that the accuracy should be very very close to hundred =20
percent as there is no extraction process involved. Does anybody do =20
this apart from doing a stock verification test by preparing two =20
intermediates from the two stock solutions and then injecting onto =20
the HPLC or LC-MS/MS? Is there any guideline recommending the =20
requirement to do Stock verification test? If anyone does stock =20
verification test, requesting to provide the acceptance criteria for =20
the stock verification test and also little bit of justification =20
supporting their explanation.
In short, requesting the concerned group members to elaborate on =20
different ways of preparing Calibration Curve standards and Quality =20
Control samples for conducting bioanalytical assays.
Looking forward to have contributions as there are different schools =20
of thought doing in different ways.
Regards
Neel Kamal Mohan
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The following message was posted to: PharmPK
During the accuracy and precision exercise of bioanalytical method
validation it is prudent to prepare a fresh stock for each of the six
or so
runs. Since at least two analysts are involved in the validation,
each run
provides information re to the preparations. QCs are prepared the
same way,
from the same stock as that used for standards or a different stock.
Along
these lines, the QC prepared in the sixth run are usually part of a much
larger batch, which will be used not only to support stability
exercises but
may also be used to support sample analysis. The measurement of
these QCs
in the sixth run is actually a "certification".
There is also a requirement to evaluate reference or stock solution
stability which may be used to extend the use of a stock preparation.
Measurement of this stability is performed not only against nominal
but by
logic, against an additional, independent preparation of stock.
Bridging assays, required when preparing new QCs or new standards
from a new
lot of reference material or the same lot of reference material
require and
provide stock verification.
The statistical tests perhaps should be based on equivalence or non
inferiority rather than a "t-test" since with the latter small
differences
may be exaggerated because of high precision.
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The following message was posted to: PharmPK
One other way to check stock solution, is to make a direct comparison
of two
freshly preparation (Injection in triplicate of diluted solution).
Criteria could be adjusted depending on the analytical method (2%
bias for
HPLC-UV analysis, more for LC-MS/MS).
This way could be more convenient, to save time, and to know before a
run if
solutions are correct or not. It gives a quicker response and permits to
suppress the bias due for example to the extraction process.
Multiple analysts for preparation, stability verification, and
solubility
comparison in different solvents are also possible and recommended.
Regards
Fabrice Guillet
Xenoblis
Saint Gregoire
France
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dear Neel sir,
as such there is no guideline suggesting that stock solution
verification needs to be done and even we are not mentioning any where
in our MV or study report regarding stock solution verification test.
as you have discussed various possible ways of preparing stock
solution ,as per my opinion, it s not necessary to prepare different
stock for CS and QC s ,infect preparation of WCS and WQC from same
stock solution by same analyst will give us more accuracy as precision
could be avoided! (as only one analyst gonna prepare stock)
the main concern should be to obtain accuracy close 100 as much as
possible , even in stock solution verification test you can close the
acceptance criteria as stock solution is prepared in diluent so window
of +/-15% should be get closer and it could be made to +/-10% to have
accurate WCS /WQC
regards,
Gaurav,RQA,Sparc
Regards,
Gaurav
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The following message was posted to: PharmPK
Please see page 7, 2001 Bioanalytical method validation, guidance for
the industry.
....intended storage temperature) and short-term (bench top, room
temperature) storage, and after going through freeze and thaw cycles and
the analytical process. Conditions used in stability experiments should
reflect situations likely to be encountered during actual sample
handling and analysis. The procedure should also include an evaluation
of analyte
stability in stock solution.
--
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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