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Combination Drug Development and Five Year New Chemical Entity (NCE) Exclusivity

By Charles Jaap, MBA, RAC 

The US Food and Drug Administration (FDA) recently announced that fixed-combination drugs (FCD) comprised of at least one NCE will be eligible for five years of exclusivity. [1]

The FDA explained that it has revised its interpretation of the term ‘drug’ for the purpose of exclusivity eligibility from ‘drug product’ to ‘drug substance’.

Five-year NCE exclusivity determination will apply to each drug substance in the product, not the drug product as a whole. FDA’s previous interpretation of the terms meant that FCDs containing NCEs were only eligible for three years of exclusivity. [2]

The announcement came in the form of a newly finalized guidance entitled New Chemical Entity Exclusivity Determinations for Certain Fixed-Combination Drug Products. To view the guidance, click here.

While three-year exclusivity bars approvals of the same drug products until expiry, five-year exclusivity may bar 505(b)(2) and generally bars ANDA submissions until expiry.

The obvious de facto effect is that five years of NCE exclusivity may yield greater than five years of competition-free marketing.According to regulations cited in the guidance "If a drug product that contains a new chemical entity was approved … in an application submitted under section 505(b) of the act, no person may submit a 505(b)(2) application or abbreviated new drug application under section 505(j) of the act for a drug product that contains the same active moiety as in the new chemical entity for a period of five years from the date of approval of the first approved new drug application".[3]

However, the new guidance also includes a description of FDA’s ‘Umbrella Policy’ under which the FDA has allowed certain drug products subsequently developed that contain the same active moiety to share the balance of the original product’s five-year NCE exclusivity.[4]

The FDA noted in the new guidance that combination therapy is emerging as the standard of care in certain disease settings including cancer, cardiovascular disease, and infectious disease.

Furthermore, the FDA wishes to incentivize the development of certain fixed-combination products. [5] [6]

The key to success in combination drug development is the employment of strategic planning principles beginning at project conception. The engagement of a pharmaceutical consultant with experience in 505(b)(2) submissions should be addressed at the earliest stages of development.

Pharmaceutical Development Group (PDG) is a global pharmaceutical consultant with extensive experience in the strategic development of 505(b)(2) drug products.

From identification and choice of viable candidates through ensuring the existence of cost-effective commercialization strategies, PDG is unique in its ability to comprehensively integrate products, dosage forms, populations and FDA regulatory pathways.

Please feel free to contact us for more information.

About the author

Charles Jaap is vice-president of Operations and Business Development for PDG.

The opinions and statements in this press release are solely those of Charles Jaap and do not necessarily reflect the views of PDG.


[1] Federal Register Notice: Draft Guidance for Industry on New Chemical Entity Exclusivity Determinations for Certain Fixed-Combination Drug Products; Availability

[2] "New Chemical Entity Exclusivity Determinations for Fixed Combination Drug Products": Combo Drugs Now Eligible For Five Year Exclusivity

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

[4] FDA’s New Interpretation of the Five-Year NCE Exclusivity Provisions of Federal Food, Drug, and Cosmetic Act

[5] FDA To Give FiveYear NCE Exclusivity To Combinations

[6] FDA’s New Interpretation of the Five-Year NCE Exclusivity Provisions of Federal Food, Drug, and Cosmetic Act

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