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The following message was posted to: PharmPK
Hello,
Could anyone please let me know what kind of clinical studies FDA
requires
in order to grant an approval for a generic inhaled product (e.g. an
aerosol) for which the sponsor claims to be bioequivalent with a
prototype
(reference) inhaled product of the same active? Thank you very much
K. Avgoustakis, PhD
Department of Pharmacy
University of Patras
Rio 26500, Patras, Greece
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There is no general answer.
In the case of the FDA, specific guidances are available on their web
site, that are specific to the dosage form, and sometimes to the class
of active ingredients as well.
As an example, the guidance for Metered Dose Inhalers (MDI's) and Dry
Powder Inhalers, DPI's) states, "The concept of classical
bioequivalence and bioavailability is usually not applicable for oral
inhalation aerosols".
Frank Bales, Ph.D.
Senior Regulatory Consultant
Worldwide Regulatory Affairs
PAREXEL Intl.
1000 Park Forty Plaza, Suite 500
Durham, NC 27713
Email: frank.bales.aaa.parexel.com
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The following message was posted to: PharmPK
If plasma concentrations are measurable for a reasonable period of
time, a
BE study is probably all you need.
If plasma concentrations are not determinable, then "suitably validated
pharmacodynamic methods can be used to demonstrate BE."
http://www.fda.gov/cder/guidance/4964dft.htm
I believe improvements in spirometry values have been used for generic
inhaled beta blockers.
Susan
Susan E. Shoaf, Ph.D.
Sr. Pharmacokineticist
Otsuka Maryland Research Institute
Rockville, MD
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Dear Dr. Avgoustakis:
The following two papers may be of interest:
W.P. Wallace, Drug Information Journal (1995), 29 (3), pp. 935-940
A. Bowers, ibid, pp.941-959
Regards,
Peter
Peter W. Mullen, PhD, FCSFS
KEMIC BIORESEARCH
Kentville
Nova Scotia, Canada, B4N 4H8
pmullen.at.kemic.com URL: www.kemic.com
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The following message was posted to: PharmPK
Dear Dr.Avgoustakis,
The classical approach of bioequivalence may not be applicable to the
MDIs and DPIs for inhalation while producing the generic version ( as
the systemic exposure is minimum and the plasma/blood concentrations
are not detectable usually ).Instead a pharmacodynamic equivalence is
what is required in such cases.For example the generic version from
Ivax of the originator product Ventolin ( Albuterol GSK),
bronchoprovocation was the approach used to demonstrate the
pharmacodynamic equivalence. Similary other approcahes like cortical
suppression, histamine challenge etc. can be used but the dose response
curve should not be flat.Even for the CFC to HFA transition products (
under montreal protocol)with generic status this is applicable but two
products should be equivalent dose by dose basis.
This is applicable to all ANDAs ( MDIs/DPIs) in US, if the applicant
could not find a scientifically justified approach to prove
pharmacodynamic equivalence then clinical endpoint determination will
be the only option left that is a costly and resource intensive work.
Hope this answers your querry.
Kind regards,
Pradeep S. Bhadauria
Research Sentist
Ranbaxy Research Laboratories
INDIA.
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