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Dear All.
Incurred sample reanalysis is an evaluation where a seleced no of study samples are re-analysed and the results are compared with origional analysis. This reconfirms the bioanalytical method as there is a difference between spiked QC's and study samples.
So now an SOP must be in place to govern ISR.
POINTS TO BE DISCUSSED:
1) When It should be conducted ...during / completion / early in the study?
2) Is it necessary to conduct ISR for both FAST and FED study or each study?
3) No of ISR samples to be analysed- 5% or 10%?
4) Criteria for ISR reproducibility failure?
5) Should be part of method validation once proved no need to perform for same formulation?
6) ISR failure leads to study rejection or re-validation of method?--ISR investigation
7) should be performed in singlet or in duplicate if a sample fails (variation more than 20%).
8) should it be presented in MV report or Study report?
Method should be rugged enough & reinjection reproducibility should be high to over come ISR in dreams.
Ashish Saxena
Bio-research scientist
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The following message was posted to: PharmPK
Dear Ashish,
As I understand, ISR is not yet a regulatory requirement and there is
lot of discussion happening on the subject. Article below has a good
discussion of all the points you have raised, including statistical
treatment of example data.
"Confirmatory Reanalysis of Incurred Bioanalytical Samples (The AAPS
Journal 2007; 9 (3) Article 40"
http://www.aapsj.org/
While respecting the spirit of all regulations, I have a question which
bothers me all the time- Why bioanalytical data should be subjected to
such a rigorous scrutiny? Because of such strict requirements, life of
an analytical chemist is always stressed and there is tendency to
doctrine the data. (May not be with everyone, but I know examples.)
As always discussed in this forum about reporting BLQ, there is an
urgent need to voice the concerns of Bioanalytical scientists and make
the regulations more meaningful and useful. Otherwise Bioanalysis will
be just a regulatory requirement and has no scientific usefulness.
Regards,
Vinayak
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The following message was posted to: PharmPK
Dear Vinayak:
My understanding is that starting from 2009 ISR is required.
I was always wondering how reproducible the bioanalytical method is in
the production environments (running real samples instead of spiked
samples). Since the implementation of the ISR, I have seem several
incidences of failed ISR and the main root causes for these failures
are poor sample stability; poorly developed methods or poor execution.
ISR encourages method developer and analysts to be more diligent and,
I hate to say it but it is true, be more honest. Current industry
standard practice ISR SOP does not address all the analytical method
reproducibility issues but is a good start. Representing sponsors, I
am all for properly designed and executed ISR.
Regards,
TK
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Please find below my comments in '()'. You need to prepare a SOP, which includes your entire query's answer.
So now an SOP must be in place to govern ISR.
POINTS TO BE DISCUSSED: 1) When It should be conducted ...during / completion / early in the study? Ans:(Cover all three stages min three times)
2) Is it necessary to conduct ISR for both FAST and FED study or each study? Ans: (Yes)
3) No of ISR samples to be analyzed- 5% or 10%? Ans: (Small study 10% large study 5%)
4) Criteria for ISR reproducibility failure? > Ans: (67 % should be within 20%)
5) Should be part of method validation once proved no need to perform for same formulation? Ans: (No, should be study specific)
6) ISR failure leads to study rejection or re-validation of method? Ans: (ISR investigation Depends on data ,find root cause and take decision)
7) Should be performed in singlet or in duplicate if a sample fails (variation more than 20%). Ans: (refer clause 4)
8) Should it be presented in MV report or Study report? Ans: (Study report since it is study specific not method specific)
Regards,
Sudipta Basu
Senior Research Scientist (DMPK)
Sai Advantium Pharma Ltd.,Pune
E-Mail : sudipta.b.aaa.saiadvantium.com
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The following message was posted to: PharmPK
Hi Sudipta,
My understanding is, ISR is still not a regulatory requirement, but
discussion is on. I may be wrong. Will you please give regulatory
guidance reference?
Regards,
Vinayak
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The following message was posted to: PharmPK
Dear Vinayak,
Yes, you are right. Till now there are no guidelines for ISR. USFDA had published it in their latest meeting review as a recommendation.
Recently they have given 483 or asked to do ISR to some major Indian companies and they have already started ISR analysis.
I will send you the link or document (recommendation doc.) soon.
Regards,
S.Basu
Senior Research Scientist (DMPK)
Sai Advantium Pharma Ltd.,
E-Mail : sudipta.b.-a-.saiadvantium.com
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The following message was posted to: PharmPK
Dear Vinayak,
Please find below the details as desired.
The AAPS Journal 2007; 9 (3) Article 40
http://www.aapsj.org/
Themed Issue: Bioanalytical Method Validation and Implementation: Best Practices for Chromatographic and Ligand Binding Assays Guest Editors - Mario L. Rocci Jr., Vinod P. Shah, Mark J. Rose, Jeffrey M. Sailstad
Confirmatory Reanalysis of Incurred Bioanalytical Samples Received: August 28 , 2007 ; Final Revision Received: September 14 , 2007 ; Accepted: September 14 , 2007 ; Published: October 5 , 2007 Mario L. Rocci, Jr. , 1 Viswanath Devanarayan , 2 David B. Haughey , 1 and Paula Jardieu 1 1 Departments of Bioanalytical Sciences and Product Development, Prevalere Life Sciences Inc., Whitesboro, NY 2 Global Statistics & Data Management, Abbott Laboratories, Parsippany, NJ
Regards,
Sudipta Basu
Senior Research Scientist (DMPK)
Sai Advantium Pharma Ltd.,Pune
E-Mail : sudipta.b.at.saiadvantium.com
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It would be wise to set something functional up for ISR and begin using it.
--
Edward F. O'Connor
78 Marbern Drive
Suffield, Ct 06078-1533
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The following message was posted to: PharmPK
Hi Sudipta,
This is not a FDA guideline. Vishwanathan et al have suggested ways to
go about ISR analysis. I quoted this very same artlicle at the start of
the thread. FDA is unfair, if they have issued 483 stating the reson
that ISR analysis is not done. It is not a FDA requirement yet.
Regards,
Vinayak
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The following message was posted to: PharmPK
Dear Vinayak,
Whatever may be the reason, USFDA started giving 483 and recommendation that is for sure. May be they will implement the same soon in their upcoming guideline.
Regards,
S.Basu
Senior Research Scientist (DMPK)
Sai Advantium Pharma Ltd.,
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