OBJECTIVES : Previous data have showed that sales and loss of exclusivity/patent could impact generic drug entry; however, little is known about factors that influence abbreviated new drug application (ANDA) submissions. The purpose of this study was to examine factors associated with the likelihood of first ANDA submission for a reference-listed drug (RLD).

METHODS : A cross-sectional study was conducted using data from publicly available Orange Book database (November 2017). Other sources include FDA’s Product-Specific Guidances (PSGs), National Drug Code database, internal FDA ANDA submission data (7/01/2009-06/30/2017), and IQVIA expenditure data. Two groups, i.e., RLDs with new chemical entity (NCE) exclusivity (i.e., NCE) and without NCE exclusivity (i.e., non-NCE), were categorized. Two Cox (NCE and non-NCE) models were used to determine factors associated with the likelihood of first ANDA submissions.

RESULTS : We analyzed a total of 441 RLDs with potential ANDA submission dates which for NCE group was defined as earliest lawful ANDA filing dates (after 4 years of exclusivity with Paragraph IV certification), and for Non-NCE group was defined as product approval dates. Of these, 141 RLDs (32%) have/had NCE exclusivity. For NCE group, annual sales were the only factor associated with increased events of first ANDA submission (i.e., likelihood of occurrence of first ANDA submission). Specifically, adjusted hazard ratio for RLDs with sales > $250 million was approximately 10 times higher than those with sales < $10 million (HR;10.13, 95%CI;4.13-24.87). Contrastingly, for non-NCE group, factors associated with increased events were having Risk Evaluation and Mitigation Strategies (REMS), PSGs, being capsule/tablet or modified-release dosage form. Additionally, factors associated with decreased events were being complex dosage forms and anti-infective/antiviral therapeutic class(all P<0.05).

CONCLUSIONS : Several factors may impact the likelihood of first ANDA submissions, e.g., PSG availability appears correlated with high likelihood of ANDA submissions. Research on standards for complex products may facilitate ANDA submissions.