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I need to know how to obtain a bioequivalence waiver for an oral
formulation of a prodrug that is activated by oxidative metabolism by
both hepatic and intestinal mucosal enzymes. I will be very grateful
to anybody who gives me an answer.
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I would say that the fact that the compound is a prodrug is irrelavant
to the biowaiver. If the rate and extent of absorption is the same
compared to the brand, you have a good case for a biowaiver. The
activation to the active moiety in the body is not affected by the
formulation and can be assumed to follow an identical course as the
brand.
Milind
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but if there is significant metabolism by the gut mucose part of the
dose will be converted to the active drug before absorption and this
can complicate the matter, so what should be done to obtain a
bioequivalence waiver in this case?
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Based on my experience, you may still have to do a fed and fasted BA/
BE studies, there are certain criterion to receive biowaivers for a
Generic product if the product is going to be submitted to the FDA.
The product has to be an immediate release dosage form with BCS 1
characteristics. Biowaivers are also requested for additional
strengths if they are dose proportional with similar drug release
characteristics (F2 value >50). With prodrugs the situation me get
complicated.
For additonal help you could visit the link below to the guidances at
the FDA website
http://www.fda.gov/cder/guidance/3618fnl.htm
http://www.fda.gov/cder/guidance/5356fnl.htm
Cheers
Manish Issar, Ph.D
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