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The following message was posted to: PharmPK
When developing a dosage form of certain medication (tablet form) that
already exists in the market using a different delivery system
(modified release e.g. microcrystalline or microemulsion formulation)
which enhances absorption but produces the same pharmacokinetic
parameters of the original product ( the new delivery system allows
for a reduction in the strength) e.g. 10 mg tablet (currently marketed
product) is equivalent to 8 mg tablet (of the new product) with
regards to pharmacokinetic parameters, would regulatory authorities
request a clinical /pharmacodynamic study ( considering this new
product a new molecule) or they will accept a BE study (considering it
a generic formulation)?. The EMEA and FDA's guidance on BE require the
generic drug to have the same strength of the brand to conduct a BE
study. I was trying to find supporting documents on both agencies'
websites with no luck!. Any insights will be appreciated.
Ahmed Aljedai, Pharm.D., M.B.A., BCPS
Department Head, Medication Safety & Clinical Support
Pharmacy Division
Senior Clinical Pharmacist/ Solid Organ Transplant
King Faisal Specialist Hospital & Research Centre
P.O. Box 3354
Riyadh, 11211
Saudi Arabia
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The following message was posted to: PharmPK
Ahmed,
You should explore the regulatory path of fenofibrate where reduced dose
strengths of more bioavailable formulations were approved.
http://findarticles.com/p/articles/mi_m3374/is_16_23/ai_79868922
Might check out Arzneimittelforschung. 2002;52(3):200-4 Randomised
crossover studies of the bioequivalence of two fenofibrate formulations
after administration of a single oral dose in healthy volunteers.Sonet
B, Vanderbist F, Streel B, Houin G.
Susan Shoaf
OPDC
Rockville MD 20910
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The following message was posted to: PharmPK
Ahmed,
The Japanese NIHS has published some guidelines for this particular
issue. Check the following:
http://www.nihs.go.jp/drug/be-guide(e)/strength/strength.html.
Khalid Alkharfy
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Dr. Khalid,
Thanks for your help and the link but even this guidelines did not
address the point I was asking about.
Ahmed Al-jedai, Pharm.D., M.B.A., BCPS
Head, Medication Safety/Clinical Pharmacy Support Services
Senior Clinical Pharmacist, Solid Organ Transplant
King Faisal Specialist Hospital & Research Centre
MBC-11
P.O. Box 3354
Riyadh, 11211
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The following message was posted to: PharmPK
Dear Ahmed
This may be a case that qualified for an application [to US FDA] under
section 505 (b) (2).
Refer Guidance at link:
http://www.fda.gov/cder/guidance/2853dft.htm
The HNV study that you may conduct with formulation will be BA study and
all (almost) MR formulations need to be studied under fasting and fed
state
conditions. [This would not be a BE study].
Further, the concept of increased absorption and lower dose [10 mg vs 8
mg], will have to show that overall exposure of MR 8 mg is similar (in
bio-availability) to 10 mg IR, which will have both safety (high
exposure)
and efficacy (low exposure) implications. Assuming that PK in HNV is
similar to PK in target patient population, the BA studies need to
generate
sufficient data that can be discussed and extrapolated (PK-PD) for the
patient population, with appropriate reference to the clinical exposure
data of the original IR drug [505 (b) (2)].
In an alternative scenario, a bridging clinical study may be conducted/
required.
Regards,
Pankaj
--
Dr Pankaj Goyal, MD
Associate Director - Medical Affairs (BFRoW)
Dr Reddy's Laboratories Ltd.
White House, Block III, 5th Floor, A - Wing
Kundanbagh, Begumpet. Hyderabad - 500 016. AP. INDIA.
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