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Dear Forum members,
We are developing extended release formulation with total 5 strengths
having linear PK and dose-weight propotional formula like innovator.
We are planning to register the product in EU market as a generic
version.
As per modified release guideline of EMEA; Fast study on each strength
is required. Steady state study on higher strength only is acceptable
if linear PK and dose-weight propotional formula is there.
If it is a linear PK with dose-weight propotional formula then is it
really required to conduct a fast study in each strength?
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The following message was posted to: PharmPK
Dear Hiren,
Yes fasting study is required for all the lower strengths as you claim
your product as an extended release dosage form.
Thanks,
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Dear,
Its is clearly mentioned in guideline,
For Steady state study on higher strength only is acceptable
if linear PK and dose-weight proportional formula is there.
So for such category of drug study perform on higher strengh.
Based on higher strength study, waivers for lower strength can be
considered.
Correct me if I am wrong.
Regards
Hemant
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The following message was posted to: PharmPK
Dear Hiren,
Your argument is valid but we all understand the rigidity that is
generally faced with regulatory agencies while putting forward one's
arguments. You may give it an attempt by submitting dissolution
profiles of the strengths that you feel should be waived against the
one that will be subjected to bio studies (fed, fasting and steady
state) and for a better support to your argument try submitting IVIVC.
You will have to be patient as the delays would be unavoidable. The
real question would be that can we afford to have all these delays
while practicing commercial research??
Regards
Manoj K. Paruthi, Ph.D.
Sr. Manager, R&D
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Dear KrishnaMurthy,
Thanks for the prompt reply.
Just one thing i am not getting is if we read between the lines they
are giving us option if we want to conduct a multiple dose study (in
place of fast study on each strength) then it is allowed with highest
strength only. (may be due to have an idea of accumulation if at all
it is there after multiple dosing).
This is not mere a question of reducing the number of studies but also
to optimize the exposure to healthy volunteers on ethical ground.
Humble request to all the forum members to share their views/
experiences.
Regards..
HM
Regards.....
Hiren Mehta
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Dear Mehta,
As per European Union guidelines (CPMP/EWP/280/96, NOTE FOR GUIDANCE
ON MODIFIED RELEASE ORAL AND TRANSDERMAL DOSAGE FORMS: SECTION II
(PHARMACOKINETIC AND CLINICAL EVALUATION)) , its necessary to conduct
fasting studies on each strength and steady state study on the highest
strength for extended release tablets if it's a single unit
formulation if it follows linear pharmacokinetics and dose
proportionality.
For multiple unit formulations of a medicinal product showing linear
pharmacokinetics with multiple strengths a single dose study under
fasting conditions on the highest strength is sufficient, provided
that the compositions of the lower strengths are proportional to that
of the highest strength, the formulations contain identical beads or
pellets and the dissolution profiles are acceptable.
It may be necessary to conduct a fed study if its a enteric coated
formulation.
Regards,
Dr.S.Gunasakaran, MBBS, MD.,
Medical Affairs
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