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Dear all,
Out of curiosity: is it common practice to (be able to) request confirmatory reassay of clinical samples, based on pharmacokinetic evaluation (e.g. if a data point deviates in a PK profile)?
Regards,
Johan
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Hi all,
In the new (draft) EMEA guideline is stated that:
"Normally reanalysis of study samples because of a pharmacokinetic reason is not acceptable. This is especially important for bioequivalence studies, as this may affect and bias the outcome of such a study. However reanalysis might be considered as part of laboratory investigations, to identify possible reasons for results considered as abnormal and to prevent the recurrence of similar problems in the future."
http://www.emea.europa.eu/pdfs/human/ewp/19221709en.pdf
Regards,
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Dear Johan,
Regarding the practice of allowing or requesting confirmatory assay of samples for PK reasons, it is a typical practice for bioanalytical labs to have an SOP that describes when the lab itself may allow reassay of samples (with proper authorization), such as when drug is found in placebo subject samples. This is most often to address the possible switching or mislabeling of samples. In order to allow reassay of other samples that do not fit an expected PK profile, it is typical for the SOP to require direction for reassay from someone with authority for the conduct of the study, such as the study monitor or the clinical pharmacologist. It is also common to have an SOP that describes the process for requesting and authorizing reassay of samples whose concentration values do not fit other types of expectations, and CROs may require a sponsor to have such an SOP before they will reassay samples for such reasons.
Reassay should be used very sparingly and the reasons need to be well documented, as it may be viewed by regulatory authorities as retesting to get a desired value. Rather than reanalyzing suspect samples, it may be better to analyze the results pharmacokinetically both with the suspect value included and excluded ("censored").
-Tom
Thomas L. Tarnowski, Ph.D.
Bioanalytical Development / Analytical Development
Elan Pharmaceuticals, Inc.
800 Gateway Boulevard
South San Francisco, CA 94080
thomas.tarnowski.-a-.elan.com
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The following message was posted to: PharmPK
Johan,
Absolutely not. Firstly, how would you know which sample is correct.
Secondly, the method may not be validated for the longer-term storage.
You CAN question a method or its validation, but you would be questioning
all of the samples, not just one, and that assumes you have a reason to
question the whole method.
You can request the sampling site to check the label, as there is "some"
opportunity for error in that process.
Bottom line, a GLP (or in spirit) lab may agree to resample just to prove
they are not afraid to do it, but if they are smart, they won't.
Hope it helps,
-Shawn
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If you are the study director or PI and you have justification/rationale, and you have re-analysis described in SOP or protocol. The big point here is separation. Not to have the analytical group re-analyze reflexively because the sample result looks "funny".
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The following message was posted to: PharmPK
Hi Johan,
As already pointed out by experts in the forum, that regulatory agencies are not encouraging the reanalysis of samples for Pharmacokinetic reasons. The bottom line is that we need to have SOP's in place with clear cut mention of the reasons for repeat analysis and for acceptance criteria too. The sample can be reanalyzed for bioanalytical reasons such as internal standard variation, needle motor failure, peak shape, bad chromatography etc., However if the sample to be repeated is analytically fine then some CRO's have a code called "anomalous value" for such repeat analysis. But one should prevent such re analysis, as much as possible.
The regulatory agencies are also interested in looking the PK data with the original and with the reanalyzed value.
Hope it helps
Tausif Ahmed, Ph.D.
DMPK, Sai Advantium Pharma Ltd., Pune
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Hi john
Confirmatory re test is a worst thing to do. Ultimately it will question your analytical methodology, Better one should try to investigate the root cause of "anomalous value" with proper documentation, and if it is really an analytical error then one shall repeat the sample.
Regards
Rajanikanta Sahu
Saiadvantium.com
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