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I have certain queries related to analysis of BE studiy samples.Can
any body clarify?
1. What is the role of QC samples in a BE studies?
2. Can the chemist who is analysing the subject samples, prepare the
QC samples or some different person?
3. Are QC samples to be stored with subjects samples in the deep freezer?
4. Should QC samples be blinded?
Thanks
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sonu,
With regard to your questions, see below.
1. The role of QC samples in BE testing is to ensure that the
analytical method is working during the time samples are assayed.
Certain problems can arise that are only appearent from QC results
such as loss of detector response, injecter plugs etc.
2. Either one.
3. Yes, QC samples are most appropriately stored with the study samples.
4. QC samples need not be blinded. This is a matter of opinion
however. My opinion is that it is better to evenly distribute QC
samples throughout the run.
Best Wishes, Tom
H. Thomas Karnes Ph.D.
Professor and Director of Analytical Laboratories
Virginia Commonwealth University School of Pharmacy
Department of Pharmaceutics
PO Box 980533
410 N 12th Street
Richmond VA 23298-0533
E-mail : tom.karnes.-a-.vcu.edu
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QC samples provide surety that the method, including storage, handling,
extraction and analsys are performing acceptably (or not).
Depends on how that is written in the protocol or SOP. Large facilities
have manpower to support a QC department. They generate QC samples for
anlaysis. Smaller labs, most CRO, have the analyst produce QC. Larger ones
may have a validation split between a development unit and a production
unit.
QC may be stored in parallel (separately) to the actual samples. Storage
and handling should mimic actual sample storage and handling.
On blinding; again depends on the size of the lab. QC are used to judge
performance and to accept or reject a sunor part of a run. The analyst
should be able to determine if the run is acceptable and to do this they
would need to know the QCs. A second layer of review (unblinded) can be
added but the cost in manpower and time is usually prohibitive. Ideally
though, that would be the best approach, and in cross validations (between
labs) this is the case.
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[A few replies - db]
From: "RAKHI JAIN"
Date: Tue, 17 Sep 2002 10:13:11 +0530
To: david.-at-.boomer.org
Subject: Re: PharmPK Analysis of QC samples
Hi there
The random QC samples distribution in a sample batch of one or more
subjects ensure the correct estimation of drug. Any problem during the
analysis like Improper sample processing, Autosampler choking, etc. can be
find out with the help of QC samples. The QC samples should be processed
along with the study samples and should be distributed randomly. USFDA
has mentioned about the batch acceptance criteria for BE study which
indicates the number of QC samples injected and should be in the acceptance
limit of + 15%.
Ideally at the time of carrying the activity of Spiking solution check of
CC samples for bulk spiking, QC samples prepared by a different analyst
should also be injected. The project analyst should then inform the back
calculated concentrations to the person who has prepared the QC samples.
Once he or she is satisfied with the aqueous concentration then only the
bulk spiking should be carried out.
The spiked QC samples should be stored in deep freezer in along with the CC
samples and study samples to match the storage conditions of Study samples
and CC samples.
Thanks
Ashish Jain, M.Pharm.
Head- Bioanalytics
Wellquest Clinical Research
Email: rjain.aaa.nicholaspiramal.co.in
---
From: Vishwottam K N
Date: Mon, 16 Sep 2002 23:26:08 -0700 (PDT)
To: david.aaa.boomer.org
Subject: Re: PharmPK Analysis of QC samples
Dear Sonu,
1. What is the role of QC samples in a BE studies?
Quality control samples which are also known as
ëSeeded controlsí,
Seeded controls (sometimes called ìspikesî) are a
valuable component of in-study quality assurance.
Control samples at three or more concentrations are
prepared in plasma in bulk at the time of pre-study
assay validation, or at the time of study sample
collection, and are aliquoted into storage vessels.
A control for each concentration is assayed on each
occasion that study samples are assayed, and the
concentration determined by reference to that day's
calibration standards. If the concentration values
determined for the controls are not within ±15% of the
expected concentrations, the batch should be
considered for re-analysis. If not within ±20% of the
expected concentrations, the batch should be
re-analysed unless there is very good reason not to do
so.
Seeded controls, therefore, provide a constant
reference point between batches of assays as well as
determining whether the medicine is stable under the
storage conditions used.
2. Can the chemist who is analysing the subject
samples, prepare the QC samples or some different
person?
Once the seeded controls are checked for their
accurate preparation by random sampling during
validation and / or a pretest, it doesnít matter who
prepares and who analyses.
3. Are QC samples to be stored with subjects samples
in the deep freezer?
Once again, Seeded controls provide a constant
reference point between batches of assays as well as
determining whether the medicine is stable under the
storage conditions used. So it is very much necessary
that seeded controls are to be prepared on the day of
subject sample collection and to be kept along with it
so as to ensure seeded controls also under go same
storage conditions which test samples are undergoing.
4. Should QC samples be blinded?
Not recommended, since logic goes like this,
As seeded controls also give a valuable information on
within batch accuracy and precision, and the design of
your analysis sequence will enable u to identify if a
run is failing after partial completion because of
technical reason, so that analysis of further samples
can be stopped, other wise it yields data which is
questionable. And can run sample samples in separate
sequence (provided re-injection reproducibility has
been proved in your validation protocol) so that u
save time and prevent loss of samples.
Regards
Vishwottam K N
Associate Scientist and Head,
Biopharmaceutical Research
Suven Pharmaceuticals Ltd.
Hyderabad - India
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From: Jennifer Norman
Date: Tue, 17 Sep 2002 10:13:47 +0200
To: david.at.boomer.org
Subject: Re: PharmPK Analysis of QC samples
Guidance may be sought from the FDA Guidance for Industry: Bioanalytical
MEthod Validation (May 2001, available from the site www.fda.gov.
It provides insight into the thought processes behind setting up your
analytical run and the various measures taken to ensure assay integrity.
It also "suggests" acceptance criteria, which are helpful in drawing up
your own guidelines.
Regards,
Jennifer Norman
Division of Pharmacology
University of Cape Town
---
From: eric.magnan.-a-.beaufour-ipsen.com
Date: Tue, 17 Sep 2002 11:47:01 +0200
To: david.at.boomer.org
Subject: Réf. : PharmPK Analysis of QC samples
Hi,
you will find all you need in this paper issued after the last Washington
Conference
SHAH VP et all. Bioanalytical Method Validation : revisit with a decade of
progress, Pharmaceutical research 2000, Vol : 17, Num : 12, p.: 1551-1557 :
Best regards
Eric MAGNAN
BEAUFOUR IPSEN - Ipsen Pharma Biotech
Dpt Contrôle Qualité/Quality control Dept
Service Pharmacologie/Pharmacology Unit
eric.magnan.-at-.beaufour-ipsen.
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