Regulatory Focus™ > News Articles > In Shift, FDA to Allow Fixed-Dose Combination Drugs to Obtain Five Years of Market Exclusivity

In Shift, FDA to Allow Fixed-Dose Combination Drugs to Obtain Five Years of Market Exclusivity

Posted 21 February 2014 | By Alexander Gaffney, RAC

In the US, pharmaceutical manufacturers who obtain approval to market a "new" drug from the US Food and Drug Administration (FDA) are eligible for varying degrees of market- (rather than patent-) based exclusivity.

For so-called "new molecular entities," that means five years of protection during which time FDA will not approve any generic equivalents. For "new" drugs that represent a new use for an old drug, or a new dose of an old drug, FDA is able to grant three years of patent protection.

But what happens when a company files a new drug application (NDA) for a drug that includes botha new molecular entity (NME) and an already-approved drug in a fixed-dose combination (FDC)?


As Focus wrote last year, this is an issue that has already attracted the attention of companies and FDA alike.

In a Citizen Petition filed by Bayer in July 2013, the company argued that FDA had improperly given its FDC drug Natazia (dienogest and estradiol valerate) only three years of exclusivity.

Prior to FDA's approval of Natazia, it had never before approved a drug containing dienogest. It had, however, approved estradiol valerate in 1954.

Bayer's Citizen Petition goes on to argue that under the Federal Food, Drug and Cosmetic Act (FD&C Act), all FDCs containing an NME should be entitled to five years of market exclusivity-an argument supported by Ferring Pharmaceuticals and Gilead Sciences, both of which had filed similar petitions with FDA.

Read Regulatory Focus' Prior Coverage, Bayer: FDA's Exclusivity Provisions for Fixed-Dose Combinations Illegal, Should be Longer

New Draft Guidance

The good news for Bayer, Gilead and Ferring: FDA has listened to your petitions and, in a shift in existing policy, agrees with you.

The bad news for those same companies: Unfortunately, the policy is only applicable going forward, meaning existing products will be out of luck.

In a draft guidance issued on 21 February 2014, FDA said it was changing its "interpretation of the five-year NCE exclusivity provisions as they apply to certain fixed-combination drug products," noting that it has historically only given them three years of protection.

"The Agency recognizes that fixed-combinations have become increasingly prevalent in certain therapeutic areas (including cancer, cardiovascular, and infectious disease) and that these products play an important role in optimizing adherence to dosing regimens and improving patient outcomes," FDA wrote. "As further discussed below, we are therefore revising our historical interpretation of the 5-year NCE exclusivity provisions to further incentivize the development of certain fixed-combination products."

New Interpretation

FDA's new analysis of the FD&C Act's exclusivity provisions largely adopts industry's view of the same provisions. Specifically, FDA is changing its historical definition of the term "drug"-historically taken to mean "drug product"-to reflect "drug substance."

As a drug product, if a product contained an already-approved active moiety, it would not be seen by FDA as an NME. However, as a drug substance it would be, and would thus be eligible.

"Accordingly, a 5-year NCE exclusivity determination will be made for each drug substance in a drug product, not for the drug product as a whole," FDA wrote.

"As a result, an application for a fixed-combination submitted under section 505(b) of the FD&C Act will be eligible for 5-year NCE exclusivity if it contains a drug substance, no active moiety of which has been approved in any other application under section 505(b).30," FDA explained. "For example, a fixed-combination drug product that contains a drug substance with a single, new active moiety would be eligible for 5-year NCE exclusivity, even if the fixed-combination also contains a drug substance with a previously approved active moiety."

Comments on the draft policy are due to FDA by the end of April 2014.


Guidance for Industry:  New Chemical Entity Exclusivity Determinations for Certain Fixed-Combination Drug Products

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