FDA research reveals factors that can be used to predict the likelihood of generic drug declarations

Researchers at the FDA's Center for Drug Review and Research (CDER) are studying how drug properties, regulatory actions, and economic factors affect the availability of generics for branded drugs.
estimates that generics have saved the U.S. about $2.2 trillion in health care costs over the past decade.
but many branded drug products do not face generic competition.
In order to identify measures to accelerate the development of generic drugs, CDER researchers investigated a number of factors in a recent article entitled "Factors that affect the simplification of the declaration of new drug applications (ANDA) applications (Factors of the AndA) and factors that can predict the likelihood of ANDA submitting to the FDA based on a given reference (approved) drug."
researchers compiled ANDA-related patent data and other internal or public information maintained by the FDA, as well as published information about drug sales, to see if the characteristics of the drug or factors related to its regulatory history or marketing could be used to predict the submission of an ANDA.
researchers collected all ANDA filings legally filed for 400 branded drugs between 2011 and 2017.
of these 400 drugs, 140 were originally approved as new chemical entities (NCE) and 260 did not have an NCE franchise (and therefore were subject to generic competition immediately after approval).
analyzed the factors that affect the likelihood of ANDA reporting for each of these two groups of drugs.
this isn't the first time CDER researchers have explored the factors that predict ANDA filings, and last year the same group of CDER researchers published an article on how to accurately predict the first ANDA filing time for new chemical entities.
found that more than half of NCE products have ANDA declarations within the first two weeks of legally filing ANDA.
for these drugs, generic applications are more likely if branded drugs have higher market sales.
For example, if an NCE product has annual sales of more than $250 million over four years after the approval date, the andA filing probability for that product is about four times that of a product with annual sales of less than 10 million (see Figure 1).
trend was observed in non-NCE groups, but the correlation with sales was not statistically significant.
1. The researchers found that NCE drugs with higher sales were more likely to declare ANDA, while more complex drugs were least likely.
results are based on Cox Proportional Risk Analysis.
(higher risk ratio means that the drug is more likely to declare ANDA at any given time after the franchise expires.)
) HR - Risk ratio; CI - 95% confidence interval; LCL - 95% confidence interval lower limit; HCL - 95% confidence interval upper limit.
, identifying branded products as complex drugs (e.g., due to their structure, composition, or delivery) is negatively related to ANDA declarations for both NCE and non-NCE drugs.
researchers believe that the possible explanation for this result is the challenge of masting complex drugs or drugs, or the challenge of developing bioequistic methods for evaluating pharmaceutical combinations or products that use complex delivery technologies.
for non-NCE drugs, the data also show a strong positive correlation between the availability of specific product guidelines (PSGs) published prior to ANDA filing and the increased likelihood of ANDA reporting.
PSG describes the FDA's current ideas and expectations regarding how to develop generics for a specific drug or drug category, designed to help bidders determine the most appropriate way to generate the evidence needed for ANDA approval.
of ANDA for non-NCE drugs with PSG is approximately 3.8 times higher than for non-NCE drugs without PSG.
Patents have no significant impact on the likelihood of ANDA filing, consistent with previous findings that for drugs with high sales revenue, bidders challenge patents even when the patent challenge is unlikely to win, which means that higher sales are associated with the more general pre-approval patent challenge, commonly referred to as the "fourth" challenge.
researchers found that timely development of PSGs, including for complex generics, as well as priority for complex generic studies, could facilitate ANDA reporting and promote drug price competition.
retrospective study on drug characteristics, regulatory and economic factors related to ANDA filings, helps the FDA understand the impact of its practices and policies as it seeks to promote generic drug development.
study highlighted the importance of product-specific guidelines for assisting applicants wishing to submit generic applications, particularly complex generic applications.
sources: s1. Wittayanukorn S, Rosenberg M, Schick A, Hu M, Wang Z, Babiskin A, Lionberger R, Zhao L. Factors that an Have Impact on Abbreviated New Drug Application (ANDA) Submissions. Ther Innov Regul Sci. 2020 Jun 3. doi: 10.1007/s43441-020-00163-x.