Fixed-Dose Combination Drug Approvals, Patents and Market Exclusivities Compared to Single Active Ingredient Pharmaceuticals

Authors

Jing Hao, University of Massachusetts Amherst
Rosa Rodriguez-Monguio, University of Massachusetts Amherst
Enrique Seoane-Vazquez, Chapman UniversityFollow

Document Type

Article

Publication Date

10-15-2015

Abstract

Introduction

Fixed-dose combinations (FDC) contain two or more active ingredients. The effective patent and exclusivity life of FDC compared to single active ingredient has not been assessed. Objectives Trends in FDA approved FDC in the period 1980–2012 and time lag between approval of FDC and single active ingredients in the combination were assessed, and the effective patent and exclusivity life of FDC was compared with their single active ingredients.

Materials and Methods

New molecular entities (NMEs), new therapeutic biologics license applications (BLAs) and FDC data were collected from the FDA Orange Book and Drugs@FDA. Analysis included FDC containing one or more NMEs or BLAs at first FDA approval (NMEs-FDC) and only already marketed drugs (Non-NMEs-FDC). Descriptive, Kruskal-Wallis and Wilcoxon Rank Sum analyses were performed.

Results

During the study period, the FDA approved 28 NMEs-FDC (3.5% of NMEs) and 117 non-NMEs-FDC. FDC approvals increased from 12 in the 1980s to 59 in the 2000s. Non- NMEs-FDC entered the market at a median of 5.43 years (interquartile range 1.74, 10.31) after first FDA approval of single active ingredients in the combination. The Non-NMEs- FDC entered the market at a median of 2.33 years (-7.55, 2.39) before approval of generic single active ingredient. Non-NME-FDC added a median of 9.70 (2.75, 16.24) years to the patent and exclusivity life of the single active ingredients in the combination.

Conclusion

FDC approvals significantly increased over the last twenty years. Pharmaceutical companies market FDC drugs shortly before the generic versions of the single ingredients enter the market extending the patent and exclusivity life of drugs included in the combination.

Comments

This article was originally published in PLoS ONE, volume 10, issue 10, in 2015. DOI: 10.1371/journal.pone.0140708

Recommended Citation

Hao J, Rodriguez-Monguio R, Seoane-Vazquez E. Fixed-dose combination drug approvals, patents and market exclusivities compared to single active ingredient pharmaceuticals. PLoS ONE. 2015;10(10):e0140708. doi:10.1371/journal.pone.0140708.

Copyright

The authors

Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 License.