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We have an internal debate relating with GLP in metabolism studies. The
studies of metabolism (inhibition, induction, phenotype and metabolism
profiling) are conduct normally in according with the famous sentence
"in
the spirit of GLP" of several authors Bjornsson et al, 2003) , or
according with several steps as propose Walsly and Obach, 2004). The new
draft of FDA of 2006 "Drug Interaction Studies --Study Design, Data
Analysis, 2006 , don't said clearly that this kind of studies should be
conduct in GLP.
We are wondering about the necessity of conducting metabolism studies
in
really GLP or if only is necessary to conduct these in spirit of GLP
nowadays (SOP, audit...).
Other question is what do you thing that is the trend in this studies.
GLP
Compliance in future?.
In the case considered GLP are necessary what requirements are
necessary to
follow GLP in this studies? Really validated analytical methods?.
Thanks for you ideas.
Benjamin Santos Lobo PhD
Head of Departament
Pharmacokinetics and Metabolism
R&D Center. Ferrer Internacional
S.A.
08028 Juan de Sada 32 Barcelona
Tel +34 93 5093230
Fax +34 93 4112764
bsantos-research.-a-.ferrergrupo.com
www.ferrergrupo.com
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The following message was posted to: PharmPK
Here are my two cents.
We conduct metabolism studies "in the spirit of GLP". In our
experience it has not been necessary to do otherwise, although we
followed GLP quite closely. A case in point is metabolism profiling. In
these studies the analyst needs to have certain flexibility in regards
to the analytical methods used in order to acquire as much information
as possible. So, we have SOPs in place that describe how to perform
such studies including the various parameters that may be modified in a
method in order to acquire the analytical information need. This
touches on the issue of validated method and their need in GLP. In the
case of metabolic profiling, the nature of the work is such that a
validated method is too constrictive. We used qualified methods for
some non-GLP pre-clinical animal studies, which in my view are nearly
validated methods but lack the in-detailed study as validated ones.
The key, I have found, is to make sure that there are systems in place
to flawlessly track the samples, acquire and process, report and
archive the data. It all boils down to traceability and good record
keeping. If the lab has a GLP system in place, it is easier to use it
for non-GLP studies allowing for "documentable" extra flexibility when
needed.
Luis
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[I apologize if you received multiple copies of one PharmPk message
yesterday. I had one member ask about it and then I found multiple
copies in my in-box this morning. It looks like just one message
(multiple times). A hiccup with a mail server? - db]
The following message was posted to: PharmPK
dear,
i am in agreement with your concern which leads you to use the study
in sprit of GLP,
here with i am submitting my concern on that there is one article
which clarify that drug to drug interaction study should documented
and perform in terms of non-GLP (sprit of GLP).
you can access the link which mentioned about the drug interaction
study,
in addition with i prefer to use the standard which mentioned in GLP
like calibration/validation, personnel training, master record,
accountability, sanitation and hygiene, audit trial etc. should be
follow as per GLP, so study can sought good enough to justify the way
of working itself rather than the explanation.
http://dmd.aspetjournals.org/cgi/content/full/31/7/815
"Data obtained in support of drug-drug interaction studies should be
collected and documented with the same level of quality applied to
other non-GLP (good laboratory practice) preclinical metabolism and
pharmacokinetic data (i.e., signed and witnessed legal notebooks, good
electronic data audit trails). Importantly, sources of human-derived
reagents and their characterization should be well documented so that
preparation procedures can be tracked and verified. Standard within-
laboratory procedures and practices for biological reagent generation
should be developed and documented. Chemical reagents should possess
test notes for percentage of purity, including authentic standards of
metabolites used in construction of calibration curves whenever
possible. For some metabolites, chemical synthesis of authentic
standards in large enough quantities for comprehensive analytical
testing is not possible. In such cases, it must be understood that
conservation of these limited valuable materials is necessary and
that, therefore, all analytical criteria typically required for
bioanalytical standard materials will not be able to be fulfilled.
Such limitations should be documented."
hope my answer can near about the question,
expert can comment !!
paresh
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The following message was posted to: PharmPK
The "spirit of GLP" suggests that wherever possible and expedient you
will follow GLP. The corollary of this is that wherever and whenever
following GLP becomes too restrictive you will not. I suppose then you
would point out that in this section you were in the spirit whereas in
these other sections, the spirit had left.
The sentence "in the spirit of" equals "non GLP". it is easier and much
more accurate to just say the latter. You can also add that "all
relevant SOPs" were followed and as relevant, that the data were
reviewed and/or audited.
Who is going to audit you against spirits of?
--
Ed O'Connor, Ph.D.
Laboratory Director
Matrix BioAnalytical Laboratories
25 Science Park at Yale
New Haven, CT 06511
Web: www.matrixbioanalytical.com
Email: eoconnor.aaa.matrixbioanalytical.com
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