(6201 d 22:04 ago)
Posting: # 145
If the original drug was withdrawn from market by the company, what should we choose as reference drug for a BE study?
We are studying BE/BA of 200 mg- cefixime capsule. The reference drug from Wyeth has already withdrawn from market. The another approved by FDA is Lupin (200 mg tablet)is not available.
We have some 200 mg cefixime capsules imported from India and Korea. Can I choose one of them as reference drug in my study and are there any other solutions for this problem?
In the same case, I would like to ask reference drug of gatifolaxin for BE study when Tequin would be withdrawn by Bristol Mayer Squibb?
I appreciate all your advice.
(6201 d 01:09 ago)
Posting: # 146
would you please provide us with a little more informations, namely:
- in which country will the clinical part of the studies be performed, and
- in which country/countries will you go for regulatory submission.
Background: regulations differ from country to country if no reference product is (no more) registered.
(6200 d 10:29 ago)
Posting: # 147
Dear Jaime R,
Thank you for your reply.
The studies will be performed in Vietnam and results will be submitted to Vietnamese FDA frist and then some countries in ASEAN (Cambodia, Laos, Thailand, China)/Africa and US FDA finally.
Vietnames FDA has not released any instructions about doing BE studies yet.
I am looking forward your help.
(6200 d 04:49 ago)
Posting: # 151
for the ASEAN States following guideline applies:
2.5 Essentially similar products
[...] An 'innovator' product is a medicinal product authorised and marketed on the basis of a full dossier i.e. including chemical, biological, pharmaceutical, pharmacological-toxicological and clinical data. A 'Reference Product' must be an 'innovator' product. (see 3.5).
3.5 Reference and test product
Test products in an application for a generic product are normally compared with the corresponding dosage form of an innovator (see 2.5) medicinal product (reference product). The choice of reference product should be justified by the applicant and agreed upon by the regulatory authority.
If the innovator product is not available, an alternative comparator product approved by drug regulatory authority of the country can be used.
The test products used in the biostudy must be prepared in accordance with GMP-regulations. Batch control results of the test product should be reported.
Therefore you should contact the respective authorities beforehand to settle an agreement about the acceptance of your chosen reference product.
Problematic may be the acceptance of the GMP-standard (e.g., Australia accepts only the reference product marketed in Australia, the European Union accepts only European references and products from countries where a 'Mutual Recognition Agreement' exists: Switzerland-yes, USA-no...).
I don't think it will be possible to get an approval from US-FDA, since no reference listed drug product exists for cefixime...
Another case is gatifloxacin, where the reference is still marketed:
If you have performed your study with this reference, and it was withdrawn from the US market later, safety and efficacy data is still available for FDA's review staff.