On 18 Mar 2004 at 17:43:43, (helmut.schuetz.-at-.chello.at) sent the message
Dear Eric,
the report (*) of the joint conference (AAPC, US FDA, FIP, HPB, AOAC)
held December 3-5, 1990 states at
[Acceptance Criteria for the Run] - [Repeat analysis]
"The protocol for repeat analysis should be established a priori. Some
aberrant values can be identified which can be attributed to processing
errors, equipment failure, poor chromatography or QC samples outside
predifined tolerance. Cautious use of a 'pharmacokinetic fit' such as a
double peak may call for repeat analysis of some samples in the study,
but the reasoning should be clearly documented."
Some remarks from our experience (i.e., never got any deficiency letter
in that respect...):
- profiles are inspected by an PK expert in a blinded manner (data
ordered by periods, not treatments)
- only values directly influencing the main target parameters are
considered for re-analysis (double peaks, rising values in the terminal
phase)
- 'suspected PK outliers' are re-analysed
- original value verified?
no : use new analytical result
yes: discard analytical result(s), use estimate
Three procedures are laid down in SOPs and specified in the protocol:
- definition of 'influence on PK parameters'
- verification/falsification of the original result (same as for
re-analysis based on analytical grounds)
- estimation of 'discarded analytical results', e.g., linear
interpolation if ttmax,
parabolic interpolation in the area of tmax,...
Closing remarks:
Some kind of 'plausibility review of data' is just good scientific
practice.
Even if a bioanalytical method is fully validated and running under
control, interferences may exist in single samples which lead to a
false result (e.g., matrix effects in LC/MS). If you have a procedure
beforehand dealing which such problems, you are on the safe side.
Posthoc procedures (oops, let's look what we can do...) are IMHO never
accepted.
Good luck,
Helmut
(*) SHAH, V.P., MIDHA, K.K., DIGHE, S., McGILVERAY, I.J., SKELLY, J.P.,
YACOBI, A., LAYLOFF, T., VISWANATHAN, C.T., COOK, C.E, MCDOWALL, R.D.,
PITTMAN, K.A. and S. SPECTOR;
Analytical methods validation: Bioavailability, bioequivalence and
pharmacokinetic studies.
Int. J. Pharm. 82, 1-7 (1992)
--
Helmut Sch\0xB8tz Biokinet GmbH / Dept Biostatistics
Neubaugasse 36/11 Nattergasse 4
A-1070 Vienna/Austria A-1170 Vienna/Austria
tel/fax +43 1 9713935 tel +43 1 4856969 62
no cell phone ;-) fax +43 1 4856969 90
http://www.goldmark.org/netrants/no-word/attach.html
--
Dear Eric,
I forgot the current reference (*) from the Workshop 12-14, 2000 (AAPS,
US FDA):
[Acceptance Criteria for the Batch] - [Repeat Analysis]
Repeat Analysis: A standard operating procedure or guideline for repeat
analysis and their acceptance criteria must be established a priori.
This SOP or guideline should
define acceptable reasons for repeating sample analysis, such as sample
processing errors, equipment failure, poor chromatography, etc.
Cautious use of "pharmacokinetic fit" such as double peak may call for
repeat analysis of some samples in the study. The rationale for the
repeat analysis and the reporting of the repeat analysis should be
clearly documented.
The need for occasional reintegration in chromatography should be
conducted according to a priori criteria.
Samples involving multiple analytes should not be rejected based on the
data from one analyte failing the acceptance criteria. The data from
rejected runs does not need to be documented, but the fact that a run
was rejected should be filed including the reason for failure. The
documentation of accepted runs should include outlier standards and QC
samples with reasons for decision(s).
Regards,
Helmut
--
Helmut Sch\0xB8tz Biokinet GmbH / Dept Biostatistics
Neubaugasse 36/11 Nattergasse 4
A-1070 Vienna/Austria A-1170 Vienna/Austria
tel/fax +43 1 9713935 tel +43 1 4856969 62
no cell phone ;-) fax +43 1 4856969 90
http://www.goldmark.org/netrants/no-word/attach.html
(*) SHAH, V.P., MIDHA, K.K., FINDLAY, J.W.A., HILL, H.M., HULSE, J.D.,
McGILVERAY, I.J., MCKAY, G., MILLER, K.J., PATNAIK, R.N., POWELL, M.L.,
TIONELLI, A., VISWANATHAN, C.T. and A. YACOBI;
Bioanalytical Method ValidationnA Revisit with a Decade of Progress
Pharmaceutical Research 17(12), 1551-1557 (2000)
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