Back to the Top
The following message was posted to: PharmPK
Dear group,
I have to deal with the present situation and would
appreciate your comments.
We have 5 different strengths of a multisource
formulation (immediate release solid oral dosage
form).
We are going to carry out the Bioequivalence not on
the highest but on the medium strength dose for safety
reasons.
Considering that:
1-We are not talking about a narrow therapeutic range
drug product.
2- Linear pharmacokinetics was reported up to the 4th
strength
3- The different strengths of our product are
proportionally similar in their active and inactive
ingredients
4- Finally, bioequivalence is demonstrated between the
medium strength of our product to the respective
strength of the comparator product
5- The dissolution profiles are similar when comparing
against the reference product in three media for all
strengths.
Can I ask for a waiver of in vivo study for the two
highest strengths?
Thanks,
paula
Back to the Top
Hi Paula:
Whenever there are more than 3 strengths, FDA requires BE study on two
strengths. Your best bet is to contact the regulatory agencies to get their
opinion. US FDA is good in providing the feed back. Good Luck.
Raj
Back to the Top
The following message was posted to: PharmPK
Dear Paula,
I think there should be no problem up to the 4th strength.
Since you are leaving linear PK with the 5th strength, a waiver generally
is not granted.
Depending on the legislation - or better: openness of the regulatory
authority you are dealing with - I would suggest some kind of preliminary
discussion with them.
You may argue basing on the safety profile of the drug making a study in
healthy subjects unethical - resulting presumably in the requirement of a
BE study in patients.
If the substance is subject of polymorphism you may consider a BE study in
fast metabolizers only.
Etc., etc.
best regards,
Helmut
--
Helmut Sch=FCtz
BEBAC
Consultancy Services for Bioequivalence and Bioavailability Studies
Neubaugasse 36/11
1070 Vienna/Austria
tel/fax +43 1 2311746
http://BEBAC.at
Bioequivalence/Bioavailability Forum at http://forum.bebac.at
http://www.goldmark.org/netrants/no-word/attach.html
Back to the Top
The following message was posted to: PharmPK
You should arrange for a pre-ANDA meeting with the FDA to go through
your BE trial design as well as any other questions you have. The
highest strength will not be allowed and also waiver is only allowed if
you have IVIVC or class I or II.
Back to the Top
[Another break (scheduled) of a day or two now or soon) - db]
Hi Raj,
I believe you are quoting an older policy. If you see the "Guidance for
Industry, Bioavailability and Bioequivalence Studies for Orally
Administered Drug Products- General Considerations" of March 2003, Page 13,
second paragraph and its footnote, it says,
"....an in vivo BE demonstration of one or more lower strengths can be
waived based on dissolution tests and an in vivo study on the highest
strength". Footnote- "This recommendation modifies a prior policy of
allowing biowaivers for only three lower strengths on ANDAs"
But since the present case does not fit this statement completely, I agree
with you that contacting the agency is the best thing to do.
Nisha K R.
Back to the Top
The following message was posted to: PharmPK
That's not really the case. We have done it quite a few times for 4
strengths and it's true that US FDA was positive in providing their
feedback prior to submission.
Good Luck
Manoj K. Paruthi
Manager, R&D
PharmPK Discussion List Archive Index page
Copyright 1995-2010 David W. A. Bourne (david@boomer.org)