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. 2022 May 20;3(5):e221096.
doi: 10.1001/jamahealthforum.2022.1096. eCollection 2022 May.

Approvals and Timing of New Formulations of Novel Drugs Approved by the US Food and Drug Administration Between 1995 and 2010 and Followed Through 2021

Ravi Gupta  1   2 , Christopher J Morten  3 , Angela Y Zhu  4 , Reshma Ramachandran  5   6 , Nilay D Shah  7 , Joseph S Ross  5   8   9   10
Affiliations

Approvals and Timing of New Formulations of Novel Drugs Approved by the US Food and Drug Administration Between 1995 and 2010 and Followed Through 2021

Ravi Gupta et al. JAMA Health Forum. .

Abstract

Importance: New formulations of prescription drugs can improve convenience and tolerability for patients, but they also constitute manufacturer strategies to extend brand-name drug market exclusivity periods.

Objective: To examine whether new formulations of brand-name novel drugs were associated with novel drugs' sales and/or therapeutic value, as well as characterize first new formulations' approval timing relative to the novel drug's generic approval.

Design setting and participants: This cross-sectional study used the Drugs@FDA database to identify all novel tablet and capsule drugs approved by the US Food and Drug Administration (FDA) between 1995 and 2010 and followed through December 31, 2021.

Exposures: Novel drugs' blockbuster status, defined as annual sales of $1 billion or greater, and therapeutic value, measured by (1) accelerated approval status, (2) World Health Organization Model Lists of Essential Medicines inclusion, (3) innovativeness, and (4) clinical usefulness.

Main outcomes and measures: Approval of a new formulation and timing relative to a novel drug's first generic's approval.

Results: Among the 206 novel drugs in tablet or capsule form approved by the FDA from 1995 to 2010, 81 (39.3%) were followed by an FDA-approved new formulation, and 167 (81.1%) had a generic version as of December 31, 2021. In multivariable analyses, new formulations were statistically significantly more likely among blockbuster drugs vs not (58.2% vs 27.6%; adjusted odds ratio [AOR], 4.72; 95% CI, 2.26-9.87; P < .001) and those granted accelerated approval vs not (50.0% vs 37.6%; AOR, 5.48; 95% CI, 1.52-19.67; P = .009), and less likely among orphan products vs not (11.8% vs 44.8%; AOR, 0.13; 95% CI, 0.03-0.52; P = .004). Essential medicine listing vs no listing (47.8% vs 36.9%; AOR, 1.32; 95% CI, 0.52-3.34; P = .56), first-in-class or advance-in-class status vs addition-to-class status (37.8% vs 40.5%; AOR, 0.71; 95% CI, 0.32-1.58; P = .40), and categorization as clinically useful vs not useful (40.9% vs 44.8%; AOR, 0.81; 95% CI, 0.34-1.92; P = .64) were not associated with increased likelihood of a new formulation. First new formulations were statistically significantly less likely to be approved after the novel drug's first generic approval (84.6% vs 15.4%; P < .001).

Conclusions and relevance: In this cross-sectional study of novel drugs in tablet or capsule form approved by the FDA between 1995 and 2010, manufacturers pursued new formulations of best-selling brand-name drugs and those granted accelerated approval but did so less frequently once generic competitors entered the market. Other measures of therapeutic value were not associated with new formulations.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Morten reported personal fees from Yale University’s Collaboration for Research Integrity and Transparency, which received grant funds from Arnold Ventures outside the submitted work. Dr Ramachandran reported serving as a board member for the American Medical Student Association Foundation and Universities Allied for Essential Medicines North America, as well as serving as US Food and Drug Administration Task Force chair of Doctors for America, whose work is supported by Arnold Ventures. Dr Ross reported grants from the US Food and Drug Administration for the Yale University–Mayo Clinic Center of Excellence in Regulatory Science and Innovation program (U01FD005938), Johnson & Johnson through Yale University, the Medical Devices Innovation Consortium as part of the National Evaluation System for Health Technology, the Agency for Healthcare Research and Quality (R01HS022882), the National Heart, Lung, and Blood Institute of the National Institutes of Health (R01HS025164 and R01HL144644), and the Laura and John Arnold Foundation outside the submitted work; in addition, Dr Ross is an expert witness at the request of relator’s attorneys, the Greene Law Firm, in a qui tam suit alleging violations of the False Claims Act and Anti-Kickback Statute against Biogen Inc. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Timeline of Novel Tablets and Capsules Approved by the US Food and Drug Administration, 1995-2010, Followed by New Formulation and Generic Version Approvals Grouped by Therapeutic Area (n = 81)
Figure 2.
Figure 2.. Timing of Novel Tablet and Capsule First New Formulation Approved by the FDA Relative to Generic Drug Approval (n = 65)
FDA indicates US Food and Drug Administration.
See this image and copyright information in PMC

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