On February 21, 2014, FDA issued a Draft Guidance that will now permit a fixed combination drug product containing a new active ingredient plus a previously approved active ingredient to qualify for New Chemical Entity (NCE) exclusivity, thereby preventing the filing of generic drug applications referencing the combination product for a period of 5 years. (A fixed combination drug is one containing more than one active ingredient, each in a fixed amount).

FDA's prior approach, in effect since 1994, had denied NCE exclusivity status to a fixed combination drug product that included an already-approved active ingredient. By virtue of the new Draft Guidance, the Agency is changing its interpretation of pertinent sections of the Federal Food, Drug, and Cosmetic Act and its own regulations. Going forward, FDA will determine NCE exclusivity by considering the newness of each drug substance (active ingredient) in a fixed combination drug product. If one active ingredient is new, NCE exclusivity can be awarded to the entire product.

As reasons for the change, FDA cites: (i) the emergence of combination drug treatment as a standard of care for serious diseases such as cancer, cardiovascular disease and infectious diseases (e.g., HIV), and (ii) the need to encourage the development of fixed combinations to treat these and other diseases, because particular combinations have been shown to improve treatment response, lower risk of resistance and lower rates of adverse events.

From a legal standpoint, FDA reasons that the term "drug" in the statute and regulations is broad enough to include a drug substance as well as a drug product, pointing to the U.S. Supreme Court's decision in United States v. Generix Drug Corp., 460 U.S. 453 (1983). (In that case, the Court ruled that a generic drug manufacturer could not avoid the new drug provisions of the Act by arguing that the term "new drug" only meant drug substance and not the entire drug product).

FDA's Draft Guidance is related to its concomitant decision on three citizen petitions seeking NCE eligibility for three combination drug products, each containing at least one new active ingredient (Gilead's Stribild, Ferring's Prepopik and Bayer's Natazia). The petitioners advanced arguments that FDA found persuasive; several were adopted by the Agency in its reasoning in the Draft Guidance. Notably, however, FDA did not award NCE exclusivity to these drugs, because they had been approved prior to issuance of the new interpretation in the Draft Guidance. In other words, the Draft Guidance will be prospective in its application.