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Dear Group members,
We are evaluating the system suitability (both HPLC and LC/MS/MS)
before start of the each batch by injecting the three injections of
the same sample (either extracted or aqueous), and the acceptance
criteria for %CV of the area ratio (drug/IS) should be with in 5%.
We also used to inject the same system suitability samples with in the
batch (batch containing CC, QC and unknown samples), one injection in
the starting of the batch and two injections in the last.
My question is, do we need to consider the same acceptance criteria
for the system suitability, which was run before start of the batch
and the one, which was run with in the batch (batch size was
approximately 120 samples)
Since in one of batch, all of my CC, QC samples are with in the
specifications and batch is passing, but the % CV of the system
suitability samples injected (one first injection and last two
injections) is more than 5% (it was 7.8%), in this situation do we
need to accept or reject the batch?
Please provide your opinion and any regulatory requirement for the
same situation.
Regards,
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CC and QC sample performance is viewed differently from that of system
suitability (SS) samples. SS samples are used to evaluate signal
stability, response, and carryover.
It may be started with 5 succesive injections (also called priming
injections) of high concentration CC.( % CV not more than 5%) followed
by a blank injection ( to assess carryover; limit 0.1%) and low
concentration SS sample (S/N .-a-. 5:1).
This is followed by CC, QC and unkown samples. At least one pair of
high SS every 40 samples plus one pair at the end of batch should be
run. The peak area ratio for each pair of high concentration system
suitability samples must be within 15% of the mean concentration of
the first five high concentration samples. You can remove a high
concentration (only one) value as an outlier using Mandel's Tn test,
in case of a failure of 15% criteria.
At the end of a batch blank sample (to assess carryover, limit 0.1%)
and a low concentration system suitability sample (S/N .aaa. 5:1) are used
to ensure proper instrument response.
Hope it helps.
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Dear Rama Rao
If your System suitability is with in the acceptence criteria of 5%
CV , Which you have injected before staring your actual batch which
is acceptable to accept you actual batch .
And as you mentioned about the injections of same system suitabilty
one in starting and 2 at the end of the batch.From which you can
cross check your RT and response of the IS and Analyte over the time
but you may or maynot expect the %CV with in the limit as if your
analysis was on LC-MS/MS.
Adding to this I could suggest the it would be good if your System
Suitability batch comprise of minimun of 6 injections.
Regards
Nagesh
Sr.RA
NEKTAR
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The sole purpose of the system suitability test is to ensure that the
instrument has performed (from start to end of a batch) in a way that
will enable this instrument to produce accurate and reproducible data.
Accepting 15% CV criteria value for System suitability samples avoids
the risk of encountering instrument drift commonly observed in LC-MS-
MS analysis.
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The following message was posted to: PharmPK
That is not system suitability. You are describing batch acceptance!
System suitability is designed to demonstrate that the system is
suitable for sample analysis prior to running any samples.
--
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.-a-.matrixbioanalytical.com
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Even if the system is found to be suitable prior to sample analysis,
its performance may vary during or at the end of analysis & ultimately
questioning the analytical results.
During a system suitability test, it is essential to keep the
evaluation of standards and quality control checks separate from
evaluation of the system suitability samples. This is because the
purpose of these samples is quite different. Standards are utilized
to calibrate the response of the method. Quality control checks are
used to mimic the treatment of an unknown and to provide an
indication as to whether steps such as sample storage, thawing,
aliquoting, extraction, analysis, and data integration were performed
as expected. It is generally perceived that quality control samples
can achieve this function of monitoring system performance. However,
quality control samples alone are not adequate for performing this
latter function ( text copied from Briscoe et al J. Pharm. Biomed.
Anal. 44 (2007) 484-491).
The case studies described in this paper clearly demands the need to
have 15% CV criteria for system suitability samples (although FDA
doesnt describe it) as that of QC samples.
hope it helps!
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Dear Rama
In your query the most important thing is what does your SOP says? You
have to follow that- if it's there , if not you will have to add the
clause before embarking on your study.
There is no regulatory requirement for your case as far as i know --
the only thing FDA mentions in method vaildation guidelines is --
There should be an SOP to ensure optimum operation of the system.
If your SOP mentions criteria 5% then I dont think it will be a good
idea to alter it, during subject analysis and in the end (more than
5%). What i feel there can't be two limits for the same activity-
otherwise it's like accepting that at the end of the study the system
is not suitable (5%CV) as it was before, this also means the values
obtained now are deviated more than previous values.
Regards
Bharat Sawnani
Wockhardt
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The following message was posted to: PharmPK
> That is not system suitability. You are describing batch acceptance!
> System suitability is designed to demonstrate that the system is
> suitable for sample analysis prior to running any samples.
.... and after.
Regards
Walter Peris
--
Walter Peris, PhD
Bioanalytical Sciences
Pharmacokinetics, Metabolism and Dynamics Department
Rotta Research Laboratorium
The R&D Division of Rottapharm S.p.A.
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Rama,
I am not a PK scientist but:
We learn during method development what the characteristics of the
method are.
We decide at that time if the characteristics are acceptable for the
required accuracy and precision.
If they are not, we redevelop the method.
If they are, we write the validation protocol about the characteristics.
Am I incorrect?
Regards,
Stan Alekman
Pharmaceutical Consultant
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The following message was posted to: PharmPK
Absolutely
--
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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