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Regulatory Focus™ > News Articles > New Fixed-Dose Combination Drugs Now Eligible for 5 Years of Exclusivity, FDA Says

New Fixed-Dose Combination Drugs Now Eligible for 5 Years of Exclusivity, FDA Says

Posted 10 October 2014 | By Alexander Gaffney, RAC

New Fixed-Dose Combination Drugs Now Eligible for 5 Years of Exclusivity, FDA Says

The US Food and Drug Administration (FDA) has finalized a new policy which will for the first time allow new fixed-dose combination  (FDC) drugs consisting of at least one new drug product to be eligible for five years of so-called "New Chemical Entity" (NCE) exclusivity. But in a setback for companies with existing FDCs, the agency will not apply the policy retroactively.


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

For NCEs, 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 just three years of patent protection.

Historically, that meant that fixed-doze combinations of drugs consisting of at least one already-approved entity were ineligible for five-year exclusivity rights for their drugs.

But in July 2013, the pharmaceutical company Bayer petitioned FDA to change the policy, arguing that federal law required the agency to grant the products five years of exclusivity. [Read Regulatory Focus' Prior Coverage, Bayer: FDA's Exclusivity Provisions for Fixed-Dose Combinations Illegal, Should be Longer]

Draft Guidance Overview

Several months later, FDA said it largely agreed with Bayer (and other companies, including Gilead and Ferring), and issued a new guidance document outlining major changes to its policy. In the guidance, New Chemical Entity Exclusivity Determinations for Certain Fixed-Dose Combination Drug Products, FDA said that going forward it would allow new "drug substances" within an FDC to be eligible for five-year exclusivity.

"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."

Not Retroactive

But while industry was largely pleased with the guidance, one aspect of it concerned them: FDA's policy wouldn't be retroactive—an odd decision since the agency said it agreed with industry's interpretation of the Food, Drug and Cosmetic Act.

In comments to FDA, the Biotechnology Industry Organization (BIO) implied that FDA's decision to only grant prospective FDCs five-year exclusivity was potentially illegal. "NCE exclusivity is governed by the FD&C Act provisions governing 505(b)(2) applications and [Abbreviated New Drug Applications]," BIO wrote. "It is not a right 'awarded to' or held by NDA sponsors from the time of their initial approval; rather, it is simply a statutory prohibition on FDA’s acceptance or approval of certain types of applications at certain times."

Ferring, one of the original petitioners to FDA regarding the FDC exclusivity issue, made a similar argument, saying that FDA's new policy concedes that five years of exclusivity is the "legally correct" interpretation. Why then, Ferring asked, was FDA not applying the law correctly to existing applications as well?

However, most comments submitted to FDA, such as those from Merck and PhRMA, were primarily concerned with making sure that FDA implemented its policy as soon as possible to ensure that new FDC products were not deprived of two years of deserved exclusivity.

Final Guidance: Sorry, Old Applications

Industry is likely to be a bit dissatisfied, then, with FDA's final version of the guidance.

Released on 10 October 2014, the guidance explains that FDA's policy will only be effective as of the date of its publication.

"Therefore, the new interpretation will not apply to fixed-combination drug products that were approved prior to the publication of this guidance document," FDA wrote. FDA notes that at least 19 NCEs have been approved that the policy could have applied to, with "more than half" of those gaining approval within the last seven years.

Several drug companies, in other words, are likely to be affected by FDA's policy.

The guidance, with the exception of several minor changes, is otherwise unchanged.


New Chemical Entity Exclusivity Determinations for Certain Fixed-Dose Combination Drug Products


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