Authorized generics and bioequivalence standards

[diana.papshev]

Anonymous member request:

"When an authorized generic emerges into the market, is the company marketing the drug using the brand's manufacturing facilities or process to produce it? That is, are the generic and the brand the same other than there out appearance of the drug per se? As an example, is Teva's version of generic Adderal XR manufactured by Shire but simply distributed by Teva? I ask this since an aNDA is not filed at the time of the authorized generic, correct.

A different but related question. It's my understanding that there are variations in "potency" from batch to batch with respect to the production of brand medications as well. For instance, brand A batch 1 may vary in the blood concentrations that would be produced versus brand A batch 2. It's also my understanding that the FDA applies the same standards of bioequivalence to different batches of brand name medications. Can you please confirm or elaborate on this topic? Thanks again for your assistance."

[chantell.reagan]

Authorized generics are marketed under the brand's NDA, therefore, there is no separate ANDA submitted. They are exactly the same as the brand (including inactive ingredients), with the only difference being the label. Authorized generics are typically marketed by the brand company's generic division or through a licensing agreement between a generic and brand companies. Typically, according to the licensing agreement, the brand company ships their product to the generic company where it's packaged under the generic company's label, as is the case with Adderall XR, as Shire ships to Teva. Technically, the generic company could also manufacture the product as long as they adhere to all the brand's standards.

According to the FDA, there are variations in absorption between brands and generics. In an analysis of approximately 2000 human studies "the average difference in absorption into the body between the generic and the brand name was only 3.5 percent." This is considered to be an expected and acceptable difference, whether for one batch of brand name drug tested against another batch of the same brand, or for a generic tested against a brand name. The FDA goes on to say that "the difference for the generic-to-brand comparison was about the same as the brand-to-brand comparison."

With regards to bioequivalence (BE), a generic product is considered to be BE to the brand if the "90% confidence interval (CI) of the mean AUC and the relative mean Cmax is between 80% to 125%". This same standard is used for testing the BE of branded products with reformulation or manufacturing changes.

Sources:
Generic Pharmaceutical Association: Authorized generics
FDA law blog 7/09
FDA: Facts and Myths about Generic Drugs
U.S. Pharmacist.Generic Drugs: History, Approval Process, and Current Challenges (6/09)