Patents v. Statutory Exclusivities in Biological Pharmaceuticals - Do We Really Need Both

Over the past decade or so, the United States has been the arena of a boisterous debate regarding the creation of a new regulatory framework for the approval of generic versions of biologics-based pharmaceutical products (also known as biological products and biologics )--an important and increasingly growing class of drugs. The basic purpose of such a framework is to create a fast and less-costly route to FDA approval for biologics that would be similar or identical to already-approved biological products--typically ones that are sold on the market at monopoly rates--thereby allowing cheaper versions of such medicines to enter the market. One of the main points of contention in creating the framework for the approval of generic biologics has been the length of the exclusivity period granted to developers of original biologics during which generic competitors are not allowed to enter the market. On March 21, 2010, as part of the healthcare reform act, Congress settled this debate by enacting the Biologics Price Competition and Innovation Act of 2009 ( BPCIA ), which provides statutory exclusivity periods of 12 to 12.5 years for original biologics from the date of FDA approval. This 12- to 12.5-year statutory exclusivity period predominantly overlaps with patent protection on the underlying biological product and is about 5 to 11 months shorter than the average remaining period of such patent protection on the original product. This redundancy raises questions regarding the need for and purpose of having patents in inventions related to biologics in addition to statutory exclusivities. What justification is there, if any, for such double-layered protection in biologics? Assuming that such justification or need for double protection does exist, why should biologics be the only kind of technology to benefit from it? Could the statutory exclusivity regime in biologics mark the dawn of a new era in the protection and incentivizing of innovation and the beginning of a gradual replacement of the old patent system with modern schemes of statutory exclusivities; or is it just a peculiar case of a legal regime shaped by an unusually powerful industry? In this Article I will seek to address these questions and propose some answers. Part I of this Article will review fundamental patent theory concepts necessary for the discussion and compare them with statutory exclusivities, with emphasis on the statutory exclusivity scheme created under the Hatch-Waxman Act. Part II will describe the current regulation of biologics in the United States and review the framework for the approval of generic biologics under BPCIA. Comparing statutory exclusivities and patent protection in the context of biologics, Part III will discuss the merits of these two regimes from a public policy perspective, address the possible ramifications of having both statutory exclusivities and patent protection in biologics, and culminate in a call for the suspension of patent enforcement rights with relation to biological products that benefit from statutory exclusivities afforded under BPCIA for the duration of such exclusivities

The Biologics Price Competition and Innovation Act 10--A Stocktaking

On March 23, 2010, President Obama signed into law the Biologics Price Competition and Innovation Act (BPCIA) as part of the Patient Protection and Affordable Care Act (“Obamacare”). The purpose of BPCIA was to create for biologics a regime similar to that of the Drug Price Competition and Patent Term Restoration Act (Hatch–Waxman Act) and, in so doing, to open biologics markets to competition and, subsequently, lower the price of these expensive and increasingly important pharmaceuticals. Using original data, this Essay takes stock of the decade that has passed since the enactment of BPCIA. This Essay surveys the state of competition in United States biologics markets, entry of follow-on biologics into these markets, and the effects such entry has had on biologics prices. This Essay’s main findings are that, as of March 23, 2020—exactly ten years since the signing of BPCIA into law—the FDA has approved a total of 26 follow-on biologics deemed biosimilar to 9 original products (ratio: 2.63 follow-on/original products), with only 16 of these deemed biosimilar to 7 original products (ratio: 1.78 follow- on/original products) actually available on the market. None of these follow-on products have been approved as interchangeable with their reference products, which means that substitution of the 7 original products with one of their 16 approved biosimilars cannot be done automatically. The price of these products was 10%–37% lower than the price of the original biologic, with the average price savings being 24% or 27%. All 35 approved follow-on and reference products are owned by a total of 11 pharmaceutical companies. The number of years of market exclusivity of the 9 original biologics before the approval of the first biosimilar ranged between 13.5–28.92 with an average of 18.27 years or 15.33–29.42 with an average of 19.87 years before the launch of the first competing biosimilar. This Essay further puts forward a new method of measuring comparative levels of competition in drug markets by comparing the ratio of total approved follow-on products per total approved original products at certain critical benchmarks. Using this measurement tool, this Essay compares BPCIA’s track record with the levels of competition in small-molecule drugs before and after the Hatch– Waxman Act, showing that that BPCIA significantly underperforms in comparison and fails to instigate levels of competition that would lead to significant price drops and increase access to biologics in the United States. A short survey of the most likely reasons for BPCIA’s underperformance follows. This Essay concludes by presenting the following question: if BPCIA’s current track record is (still) not enough to convince that it is failing to meet its goals, what more would it take to reach such a conclusion, and how much longer should policymakers wait before it is possible to surmise that BPCIA in its current form has failed to significantly increase access to biologics in the United States

Regulatory Competitive Shelters as Incentives for Innovation in Agrobiotech

This short paper is a summary of my presentation at the Michigan State Law Review 2014 Fall Symposium on “Public Domain(s): Law, Generating Knowledge, and Furthering Innovation in the Information Economy” held on October 3, 2014. The paper reviews the current role played by regulatory competitive shelters (RCSs; a.k.a. regulatory exclusivities) in the area of agrobiotech. The article also suggests that the Food and Drug Administration\u27s move to treat genetically modified animals as animal drugs under the Generic Animal Drug and Patent Term Restoration Act (GADPTRA) may result in the application of GADPTRA\u27s RCS regime to genetically modified animals and in a Hatch-Waxmanizing of the regulation of that agrobiotechnology

Bayesian inference of population size history from multiple loci

<p>Abstract</p> <p>Background</p> <p>Effective population size (<it>N</it>_<it>e</it>) is related to genetic variability and is a basic parameter in many models of population genetics. A number of methods for inferring current and past population sizes from genetic data have been developed since JFC Kingman introduced the n-coalescent in 1982. Here we present the Extended Bayesian Skyline Plot, a non-parametric Bayesian Markov chain Monte Carlo algorithm that extends a previous coalescent-based method in several ways, including the ability to analyze multiple loci.</p> <p>Results</p> <p>Through extensive simulations we show the accuracy and limitations of inferring population size as a function of the amount of data, including recovering information about evolutionary bottlenecks. We also analyzed two real data sets to demonstrate the behavior of the new method; a single gene Hepatitis C virus data set sampled from Egypt and a 10 locus <it>Drosophila ananassae </it>data set representing 16 different populations.</p> <p>Conclusion</p> <p>The results demonstrate the essential role of multiple loci in recovering population size dynamics. Multi-locus data from a small number of individuals can precisely recover past bottlenecks in population size which can not be characterized by analysis of a single locus. We also demonstrate that sequence data quality is important because even moderate levels of sequencing errors result in a considerable decrease in estimation accuracy for realistic levels of population genetic variability.</p

Calibrated Tree Priors for Relaxed Phylogenetics and Divergence Time Estimation

The use of fossil evidence to calibrate divergence time estimation has a long history. More recently Bayesian MCMC has become the dominant method of divergence time estimation and fossil evidence has been re-interpreted as the specification of prior distributions on the divergence times of calibration nodes. These so-called "soft calibrations" have become widely used but the statistical properties of calibrated tree priors in a Bayesian setting has not been carefully investigated. Here we clarify that calibration densities, such as those defined in BEAST 1.5, do not represent the marginal prior distribution of the calibration node. We illustrate this with a number of analytical results on small trees. We also describe an alternative construction for a calibrated Yule prior on trees that allows direct specification of the marginal prior distribution of the calibrated divergence time, with or without the restriction of monophyly. This method requires the computation of the Yule prior conditional on the height of the divergence being calibrated. Unfortunately, a practical solution for multiple calibrations remains elusive. Our results suggest that direct estimation of the prior induced by specifying multiple calibration densities should be a prerequisite of any divergence time dating analysis

Bayesian Inference of Species Trees from Multilocus Data

Until recently, it has been common practice for a phylogenetic analysis to use a single gene sequence from a single individual organism as a proxy for an entire species. With technological advances, it is now becoming more common to collect data sets containing multiple gene loci and multiple individuals per species. These data sets often reveal the need to directly model intraspecies polymorphism and incomplete lineage sorting in phylogenetic estimation procedures

Regulatory Competitive Shelters as Incentives for Innovation in Agrobiotech

Article published in the Michigan State Law Review