Bioequivalence and Bioavailability Forum

Dear Kotu!

❝ Please clarify regulatory acceptance by US-FDA for a study conducted for Europe region.

Zero. See the BE GL, Section 4.1.2:

For Article 10(1) and 10(3) marketing authorisation applications reference must be made to the dossier of a reference medicinal product for which a marketing authorisation is or has been granted in the Union on the basis of a complete dossier in accordance with Articles 8(3), 10a, 10b or 10c of Directive 2001/83/EC, as amended.

❝ The reference product is manufatcured in the same facility for both US & Europe and being marketed by the same brand name in both the regulatory regions.

Do you have a proof for your assumption? EMA would require an official statement by the innovator supporting your claim that the US-RLD ≡ an authorised reference in the EU. You will never get it for obvious reasons. Furthermore, are you sure that the claimed indications, recommended posology, etc. are identical (i.e., the US-label = the European SmPC)?

Hi Kotu,

❝ Please clarify regulatory acceptance by US-FDA for a study conducted for Europe region. The reference product is manufatcured in the same facility for both US & Europe and being marketed by the same brand name in both the regulatory regions.

Apart from what Helmut wrote (and which is 120% correct) it sounds to me like you ask if FDA will accept a BE study conducted on a EU-sourced reference product.
They will not. Realising this is a regulatory and legal exercise. The FD&C act sec 355 says

(blahblah): The term ‘listed drug’ means a brand name drug that is listed under section 505(j)(7) of the Federal Food, Drug, and Cosmetic Act

505(j): (j) Any person may file with the Secretary an abbreviated application for the approval of a new drug.
(...)
An abbreviated application for a new drug shall contain—

(i) information to show that the conditions of use prescribed, recommended, or suggested in the labeling proposed for the new drug have been previously approved for a drug listed under paragraph (7) (hereinafter in this subsection referred to as a “listed drug”);
(...)


So if you have sourced an EU reference product for your trial, the reference product's existence on the market is based on an EU-granted MA. The RLD in the US is another MA. It does not matter if the two are produced in the same facility somewhere by the same people and with the same batch composition etc. In some cases you may even have a confirmation from a release officer/QP that the two are completely identical, without having any positive bearing on acceptance.