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Hi,
May I request you all to kindly throw some light on the following topic.
Though it might be silly, we face practical problems with this.
While conducting bioequivalence studies of uv-light sensitive drugs
like
acitretin or isotretinoin or any other drug, we normally do the
dispensing,
dosing, sample collection, sample processing and analysis in low light
or
dimlight, either by using yellow lamps or covering normal lamps with
yellow
paper. Is this procedure sufficient enough to protect the molecule from
uv
light?
We didn't have any problems from regulatory front so far, even after
being
audited by US FDA. However, this procedure might be questioned in the
future. It would be very helpful, if we know how this situation is
handled
in other parts of the globe.
Inputs regarding this will be highly appreciated.
Regards
M.M. Ganesh
Research Scientist
Ranbaxy Clinical Pharmacology Unit
INDIA
[Do you have any data with your compounds and yellow light? - db]
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Ganesh,
The "Q1B Photostability Testing of New Drug Substances and Productss" guideline can help here.
The second part of the testing according to the guideline is to
demonstrate proper protection from light. In your case, you can filter the photostability lamp similar to theway you normally do it. If the "dosing, sample collection, and sample processing" samples pass the
test, then you have a strong story to tell. However, the photostability test lamp is very bright so this may be too harsh. Also, some of
lampdesignsheat the samples whichcan confound the test. In addition,
the filteritself may be damaged by the light/heat,which would
invalidate the test.
A stability test witha less bright light, or even the actual lights you use,still will enable you to predict stability/protection of the form: exposure forA hours caused X% degradation, but in actuality the samples are only exposed for B minutes.
Frank
Frank Bales, Ph.D.
Senior Regulatory Consultant
Worldwide Regulatory Affairs
PAREXEL Intl.
2520 Meridian Pkwy, Suite 200
Durham, NC 27713
(919) 294-5297 Phone
Email: frankbales.at.msn.com
frank.bales.at.parexel.com
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It would be very helpful if someone shares how this situation is being
hanlded at their site.
Regards
Ganesh
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Dear Ganesh,
We also follow the same procedure as you mentioned. We have handled one
product levodopa like this only. In analytical point of view we have
developed the processing methods under dim light or yellow light and in
clinical phase we have handled the dispensing as well as blood
collections in the same conditions until it was being analyzed.
Regards,
KANTHI KIRAN,
Glenmark Pharmaceuticals LTD.
INDIA.
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Dear Ganesh,
please have a look at
http://www.boomer.org/cgi-bin/htsearch?
confightdig&restricthttp%3A%2F%2Fwww.boomer.org%2Fpkin%2F&exclude&met
hodand&formatbuiltin-long&sortscore&wordssodium+vapor+lamp
(search the archive with the keywords "sodium vapor lamp").
I don't see the rationale for doing _all_ steps in a BE study in dimmed light.
* does dispensing of medications in the dark apply also to the real
world?
* cross-over conditions apply (if you apply the same conditions in
both periods, differences should mean out)
* vacutainers (glassware) give a very good protection against UV
radiation
* whole blood shows a low transparency, i.e., protecting molecules
'deeper' in the sample from any radiation
On the other hand, you will face problems in sample handling
* increased error rate in the entire clinical performance due to
reduced light (especially separation of plasma, mix-up of
samples,...)
* increased error rate in the analytical procedure (difficult
pipetting of plasma if vials are covered in aluminium foil,
reading of grading of syringes used in spiking,...)
So: is it really worth it? Just validate a set of QC ssamples
unprotected vs. protected and IMHO your fine with regulators.
Regards,
Helmut
--
Helmut Schutz
BEBAC
Consultancy Services for Bioequivalence and Bioavailability Studies
Neubaugasse 36/11
A-1070 Vienna/Austria
tel/fax +43 1 9713935
http://BEBAC.at http://forum.bebac.at
http://www.goldmark.org/netrants/no-word/attach.html
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