Public Health Product Hops

Pharmaceutical product hops extend market monopolies and increase costs, often at the expense of patients. An integral part of product life cycle management strategies by brand manufacturers, product hops often represent a last-ditch effort to preserve market share in the face of generic competition. Yet industry advocates would maintain that this is essential follow-on research and development, producing novel products that would otherwise never reach the market. Is there a middle ground between these two diametrically opposed views? Might certain product hops be considered beneficial, perhaps if they furthered important public health interests? Sometimes product hops arise due to safety concerns raised by FDA or pressure from other public health agencies. For instance, a push from Congress and the EPA to remove chlorofluorocarbons from all consumer and industrial products resulted in a switch to hydrofluoroalkane propellants in respiratory inhalers. In another instance, concerns about the opioid crisis fueled the development of abuse-deterrent formulations of opioids as part of a public health response to the crisis. Despite the public health motivations driving each scenario, I find that some public benefit may have been achieved, but at substantial expense to both payers and patients. I explore the potential benefits of a “public health product hop” in more detail using the recent push to approve over-the-counter versions of intranasal naloxone. I develop a framework for rewarding product hops that provide a meaningful and quantifiable public health benefit. In these instances, I argue for time-limited regulatory incentives that more equitably reward manufacturers for advancing important public health-goals while ending incentives for purely profit-driven product hops

Generic but Expensive: Why Prices Can Remain High for Off-Patent Drugs

Brand-name prescription drugs are sold at extremely high prices in the US because patents and other market exclusivities provided by the government allow manufacturers to exclude direct competition. This period of market exclusivity was intended for pharmaceutical manufacturers to recoup costs associated with research and development of those products and make profits. The other intended outcome of this system is that the market exclusivity period for brand-name drugs should be self-limited, with competition being able to flourish after the market exclusivities end. Such competition has been most effectively supplied by generic drug manufacturers that produce Food and Drug Administration (FDA)-approved bioequivalent versions of the brand-name product. The market entry of these generic drugs—with market uptake augmented by automatic substitution of brand-name prescriptions at the pharmacy— remains the only market intervention that lowers prescription drug prices consistently and substantially. Generic manufacturers can make their drugs available at considerably lower cost because of various market advantages they have over brand-name drugs. When this process does not operate as intended, drug prices do not fall after market exclusivity expiration, or prices for generic drugs may actually increase. In this paper, we examine the variety of factors that mitigate the cost savings associated with introduction of interchangeable generic drugs, especially older, off-patent drugs. We then consider policy solutions that may help stabilize the generic drug marketplace, diminishing the frequency and impact of generic price increases

Re-Regulating Dietary Supplements

In 1994, Congress introduced the Dietary Supplement Health and Education Act (DSHEA) to create a regulatory framework for the dietary supplement industry. Despite the increased market size of dietary supplements, the Food and Drug Administration’s (FDA) pre-market authority to regulate the introduction of dietary supplements into the stream of commerce has remained subdued. Under DSHEA, the FDA has limited authority to review dietary supplements before entering the market. Unlike pharmaceuticals, which must be proven safe and effective prior to approval and marketing, dietary supplements can be sold to consumers without such reassurances. We call on Congress to amend DSHEA to grant the FDA the additional express statutory authority to fix these problems

Dobbs in a Technologized World: Implications for US Data Privacy

In June of 2022, the U.S. Supreme Court issued its opinion in Dobbs v. Jackson Women’s Health Organization, overturning 50 years of precedent by eliminating the federal constitutional right to abortion care established by the Court’s 1973 decision in Roe v. Wade. The Dobbs decision leaves the decision about abortion services in the hands of the states, which created an immediately variegated checkerboard of access to women’s healthcare across the country. This in turn laid bare a profusion of privacy issues that emanate from our technologized world. We review these privacy issues, including healthcare data, financial data, website tracking and social media. We then offer potential future legislative and regulatory pathways that balance privacy with law enforcement goals in women’s health and any domain that shares this structural feature

Re-Regulating Dietary Supplements

In 1994, Congress introduced the Dietary Supplement Health and Education Act (DSHEA) to create a regulatory framework for the dietary supplement industry. Since the passage of DSHEA nearly thirty years ago, U.S. adults have steadily increased their annual consumption of dietary supplements. The once $4 billion industry comprising approximately 4,000 products has swelled to a$40 billion trade with anywhere from 50,000 to 80,000 dietary supplements available over-the-counter. Despite the increased market size of dietary supplements, the Food and Drug Administration’s (FDA) pre-market authority to regulate the introduction of dietary supplements into the stream of commerce has remained subdued. Under DSHEA, the FDA has limited authority to review dietary supplements before entering the market. Unlike pharmaceuticals, which must be shown to be safe and effective prior to approval and marketing, dietary supplements can be sold to consumers without such reassurances. Instead, the FDA’s authority is generally limited to post-market enforcement under DSHEA. In fact, the FDA lacks the express authority to remove dietary supplements from the market unless it can establish that the products are unsafe, adulterated, mislabeled or misbranded. Given the morbidity and mortality associated with adulterated dietary supplements and the challenges in addressing the latest fads before they cause harm, Congress must give the FDA the power it needs to be proactive. The FDA desperately needs the tools to regulate the dietary supplement industry and remove harmful dietary supplements from the market. We call on Congress to amend DSHEA to grant the FDA the express statutory authority to (1) regulate dietary supplements prior to entering the market; (2) require manufacturers to submit Supplement Labels to the FDA for pre-market review; (3) require that supplements undergo both pre-market composition testing and post-market randomized composition testing; (4) strengthen agency authority to remove adulterated dietary supplements from the market; and (5) establish an excise tax on dietary supplements

Re-Regulating Dietary Supplements

In 1994, Congress introduced the Dietary Supplement Health and Education Act (DSHEA) to create a regulatory framework for the dietary supplement industry. Despite the increased market size of dietary supplements, the Food and Drug Administration’s (FDA) pre-market authority to regulate the introduction of dietary supplements into the stream of commerce has remained subdued. Under DSHEA, the FDA has limited authority to review dietary supplements before entering the market. Unlike pharmaceuticals, which must be proven safe and effective prior to approval and marketing, dietary supplements can be sold to consumers without such reassurances. We call on Congress to amend DSHEA to grant the FDA the additional express statutory authority to fix these problems

Non-perturbative contributions to the plane-wave string mass matrix

D-instanton contributions to the mass matrix of arbitrary excited string states of type IIB string theory in the maximally supersymmetric plane-wave background are calculated to leading order in the string coupling using a supersymmetric light-cone boundary state formalism. The explicit non-perturbative dependence of the mass matrix on the complex string coupling, the plane-wave mass parameter and the mode numbers of the excited states is determined.Comment: 25 pages, 1 figure. v3: corrected minor typos, added referenc

Comparison of LC and LC/MS Methods for Quantifying N-Glycosylation in Recombinant IgGs

High-performance liquid chromatography (LC) and liquid chromatography/electrospray ionization time-of-flight mass spectrometry (LC/ESI-MS) methods with various sample preparation schemes were compared for their ability to identify and quantify glycoforms in two different production lots of a recombinant monoclonal IgG1 antibody. IgG1s contain a conserved N-glycosylation site in the fragment crystallizable (Fc) subunit. Six methods were compared: (1) LC/ESI-MS analysis of intact IgG, (2) LC/ESI-MS analysis of the Fc fragment produced by limited proteolysis with Lys-C, (3) LC/ESI-MS analysis of the IgG heavy chain produced by reduction, (4) LC/ESI-MS analysis of Fc/2 fragment produced by limited proteolysis and reduction, (5) LC/MS analysis of the glycosylated tryptic fragment (293EEQYNSTYR301) using extracted ion chromatograms, and (6) normal phase HPLC analysis of N-glycans cleaved from the IgG using PNGase F. The results suggest that MS quantitation based on the analysis of Fc/2 (4) is accurate and gives results that are comparable to normal phase HPLC analysis of N-glycans (6)

Insights into the Interaction of Heart Failure with Preserved Ejection Fraction and Sleep-Disordered Breathing

Heart failure with preserved ejection fraction (HFpEF) is emerging as a widespread disease with global socioeconomic impact. Patients with HFpEF show a dramatically increased morbidity and mortality, and, unfortunately, specific treatment options are limited. This is due to the various etiologies that promote HFpEF development. Indeed, cluster analyses with common HFpEF comorbidities revealed the existence of several HFpEF phenotypes. One especially frequent, yet underappreciated, comorbidity is sleep-disordered breathing (SDB), which is closely intertwined with the development and progression of the “obese HFpEF phenotype”. The following review article aims to provide an overview of the common HFpEF etiologies and phenotypes, especially in the context of SDB. As general HFpEF therapies are often not successful, patient- and phenotype-individualized therapeutic strategies are warranted. Therefore, for the “obese HFpEF phenotype”, a better understanding of the mechanistic parallels between both HFpEF and SDB is required, which may help to identify potential phenotype-individualized therapeutic strategies. Novel technologies like single-cell transcriptomics or CRISPR-Cas9 gene editing further broaden the groundwork for deeper insights into pathomechanisms and precision medicin