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I need your help with this.
Here is a scenario:
Standard curve range: 5, 10, 50, 100, 500, 1000, 2000, 5000, 10000 ng/mL
QC Levels: 8, 16, 800 ng/mL,
IS the QC selection acceptable for pre-clinical screening? Look
forward to hearing from you.
Thank you
Sue
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Hi,
Based on your QC selection, I assume your target drug concentration
will all be at the lower calibration curve range? If this is the
case, the higher end points will throw off the curve. You will have
to either do a weighted cal curve, or shift your calibration curve
range (if the higher end is not required).
Hope this helps.
Sherwin
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Hi Sue,
In my opinion, it is a waste of time to qualify this type of method.
Mid QC should be around middle of the curve and high QC should be
closer to the highest standard.
Regards,
Anila
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As I understand from your QC selection that you are expecting a
maximum concentration of 1000 ng/mL from unknown samples. I think it
is needless to go higher if you are expecting lower concentrations in
unknown samples.
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Dear Sue,
Regarding an assay with:Standard curve range: 5, 10, 50, 100, 500,
1000, 2000, 5000, 10000 ng/mL
QC Levels: 8, 16, 800 ng/mL,
FDA guidelines expect the low QC to be near the lower limit of
quantification the method (LLOQ), mid QC in mid-range, and high QC
near the upper limit (e.g., 75-80%). By these criteria your mid and
high QCs are too low. (I would probably raise the low QC to 2 to 3
times the LLOQ, as well.)
Tom
Thomas L. Tarnowski, Ph.D.
Bioanalytical Development
Elan Pharmaceuticals
700 Gateway Boulevard
South San Francisco, CA 94080
thomas.tarnowski.at.elan.com
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Dear Sue,
As per the guidelines you need to select your Low QC as 3 times to
your LLOQ (5 ng/mL), Mid QC concentration should be approximately 50
% of your ULOQ (10000 ng/mL) and High QC should be around 75 to 80 %
of your ULOQ.
If your calibration range is fixed, then you have to use QC
concentrations as above. But I suppose you are using a huge
calibration range, which may create problem in future.
If it is for a preclinical study of regulatory or non regulatory my
suggestion is to use the range till 1000 ng/mL and show the Dilution
Integrity to support the samples crossing your ULOQ range.
Hope this helps
Rajareddy
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Thanks to all for your reply. I agree this is not well designed assay
at all. My intention was to use full range for quantitation. Since, I
only have QC up to on 1000 ng/mL, I shouldn't use my curve above 1000
ng/mL. I will have to either dilute the samples above 1000 ng/mL or
qualify QC properly going forward.
Thanks again,
Sue
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The following message was posted to: PharmPK
If 1000 is your high QC, and you take this as 80 % of your curve then
your ULOQ would be at 1250 and you would be able to measure up to that
point. You should also validate sample dilutions up to the cMax.
Ed O'Connor, PhD
Technical Director, Immunoanalytical
Tandem Laboratories
115 Silvia Street
West Trenton, New Jersey
ed.oconnor.-at-.tandemlabs.com
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Sue you asked
" I need your help with this. Here is a scenario:
Standard curve range: 5, 10, 50, 100, 500, 1000, 2000, 5000, 10000 ng/
mL QC Levels: 8, 16, 800 ng/mL, IS the QC selection acceptable for
pre-clinical screening? Look forward to hearing from you."
This is not an unusual situation in non-clinical work where you
wanted to quantify concentration range to the 10000 and 50000 fold,
but you have to ask the question what is these extreme ranges doing
for the accuracy of the method? Needless to say accuracy
chromatography suffer and extreme ends of the standard curve I want
to address your question in following steps.
1. Adequacy of QCs " there is a misconception that regulatory bodies
require only 3 QCs with lowest QC 3xLLOQ" in my opinion this is wrong
you can add as many QCs as possible so that your reported values are
contained within at least two QCs. The best way to accomplish this is
(from the practical input from a person who had many years of shop
floor lab experience) to plot your Calibration curve range on y-axis
and expected contraptions on x-axis on a semi log plot and divide the
Y-axis into equal segments of number of QCs you wanted to introduce
(3,4,6, etc). The key is your QCs should bracket the reported
cocentrations.
2. Advantage of having more number of QCs gives an advantage of less
analytical run rejections and ability to truncate the analytical
calibration curve at high and low ends (have an SOP for reporting
analytical runs when you truncate the calibration curve)
3. If you wanted to accomplish wide range of concentrations you may
also want to consider age old concept of dual calibration curves few
people call it as a split standard curve.
4. After first few studies you really know what are the expected
concentrations and you can always refine your analytical method.
For those people who are complaining that oh no this was not outlined
in the guidance I want to advise them guidance provides minimum
requirements (that's why they are very broad) and nothing is holding
you going above and beyond and want to do a true science.
Hope this helps.
Prasad
Prasad NV Tata, Ph.D., FCP
Manager-Pharmacokinetics
Mallinckrodt, Inc.
675 McDonnell Blvd.
Saint Louis, MO 63134
Tel: (314) 654-5325
Fax: (314) 654-9325
e-mail: prasad.tata.-at-.tycohealthcare.com
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