Drug delivery using reduction-responsive hydrogel based on carboxyethyl-succinoglycan with highly improved rheological, antibacterial, and antioxidant properties.

The development of exopolysaccharide-based polymers is gaining increasing attention in various industrial biotechnology fields for materials such as thickeners, texture modifiers, anti-freeze agents, antioxidants, and antibacterial agents. High-viscosity carboxyethyl-succinoglycan (CE-SG) was directly synthesized from succinoglycan (SG) isolated from Sinorhizobium meliloti Rm 1021, and its structural, rheological, and physiological properties were investigated. The viscosity of CE-SG gradually increased in proportion to the degree of carboxyethylation substitution. In particular, when the molar ratio of SG and 3-chloropropionic acid was 1:100, the viscosity was significantly improved by 21.18 times at a shear rate of 10 s-1. Increased carboxyethylation of SG also improved the thermal stability of CE-SG. Furthermore, the CE-SG solution showed 90.18 and 91.78 % antibacterial effects against Escherichia coli and Staphylococcus aureus and effective antioxidant activity against DPPH and hydroxyl radicals. In particular, CE-SG hydrogels coordinated with Fe3+ ions, which improved both viscosity and rheological properties, while also exhibiting reduction-responsive drug release through 1,4-dithiothreitol. The results of this study suggest that SG derivatives, such as CE-SG, can be used as functional biomaterials in various fields such as food, cosmetics, and pharmaceutical industries.

Adjusting starting points for initial price offers: the example of ibrutinib.

The Inflation Reduction Act of 2022 (IRA) allows the Medicare program to negotiate drug prices beginning in 2024. Based on the guidance in the statute, CMS has selected specific data items to use to adjust initial price offers for 10 drugs in the decision-making process. Although much of the data are publicly available, some of these data items will need to be collected directly from drug companies. A 2019 US House of Representatives Committee on Oversight and Accountability investigative report collected a wide range of data from manufacturers of 12 high-revenue drugs that show what is available from the drug companies, including development costs, marketing, pricing, competition, and patent status. This article focuses on the data obtained for ibrutinib, an oral medication for treating hematologic malignancies, which is one of the only drugs reviewed by the committee that also has been selected for Medicare price negotiation. We examine data that can be obtained only from the drug manufacturer that the IRA has explicitly identified as being used to determine the price and suggest potential negotiation strategies for CMS in response.

Profits over care? An analysis of the relationship between corporate capitalism in the healthcare industry and cancer mortality in the United States.

The characteristic features of 21st-century corporate capitalism - monopoly and financialization - are increasingly being recognized by public health scholars as undermining the foundations of human health. While the "vectors" through which this is occurring are well known - poverty, inequality, climate change among others - locating the root cause of this process in the nature and institutions of contemporary capitalism is relatively new. Researchers have been somewhat slow to study the relationship between contemporary capitalism and human health. In this paper, we focus on one of the leading causes of death in the United States; cancer, and empirically estimate the relationship between various measures of financialization and monopoly in the US healthcare system and cancer mortality. The measures we focus on are for the hospital industry, the health insurance industry, and the pharmaceutical industry. Using a fixed effects model with different specifications and control variables, our analysis is at the state level for the years 2012-2019. These variables include data on population demographic controls, social and economic factors, and health behavior and clinical care. We compare Medicaid expansion states with non-Medicaid expansion states to investigate variations in state-level funded health insurance coverage. The results show a statistically significant positive correlation between the HHI index in the individual healthcare market and cancer mortality and the opioid dispensing rate and cancer mortality.

Global representativeness and impact of funding sources in cost-effectiveness research on systemic therapies for advanced breast cancer: A systematic review.

BACKGROUND: Breast cancer (BC) is the most incident tumor and, consequently, any new intervention can potentially promote a considerable budget impact if incorporated. Cost-effectiveness (CE) studies assist in the decision-making process but may be influenced by the country's perspective of analysis and pharmaceutical industry funding. METHODS: A systematic review of Medline, Scopus, and Web of Science from January 1st, 2012 to July 8th, 2022 was conducted to identify CE studies of tumor-targeted systemic-therapies for advanced BC. Articles without incremental cost-effectiveness ratio calculations were excluded. We extracted information on the country and class of drug studied, comparator type, authors' conflicts of interest (COI), pharmaceutical industry funding, and authors' conclusions. RESULTS: 71 studies comprising 204 CE assessments were included. The majority of studies were from the United States and Canada (44%), Asia (32%) and Europe (20%). Only 8% were from Latin America and none from Africa. 31% had pharmaceutical industry funding. The most studied drug classes were cyclin-dependent-kinase inhibitors (29%), anti-HER2 therapy (23%), anti-PD(L)1 (11%) and hormone therapy (11%). Overall, 34% of CE assessments had favorable conclusions. Pharmaceutical industry-funded articles had a higher proportion of at least one favorable conclusion (82% vs. 24%, p-value<0.001), European countries analyzed (45% vs. 9%, p-value = 0.003), and CE assessments with same class drug comparators (56% vs. 33%, p-value = 0.004). CONCLUSIONS: Breast cancer CE literature scarcely represents low-and-middle-income countries' perspectives and is influenced by pharmaceutical industry funding which targets European countries', frequently utilizes comparisons within same-drug class, and is more likely to have favorable conclusions.

Diversity of US participants in AstraZeneca-sponsored clinical trials.

BACKGROUND: To develop medicines that are safe and efficacious to all patients, clinical trials must enroll appropriate target populations, but imbalances related to race, ethnicity and sex have been reported. A comprehensive analysis and improvement in understanding representativeness of patient enrollment in industry-sponsored trials are key public health needs. METHODS: We assessed race/ethnicity and sex representation in AstraZeneca (AZ)-sponsored clinical trials in the United States (US) from 2010 to 2022, compared with the 2019 US Census. RESULTS: In total, 246 trials representing 95,372 patients with complete race/ethnicity and sex records were analyzed. The proportions of different race/ethnicity subgroups in AZ-sponsored clinical trials and the US Census were similar (White: 69.5% vs 60.1%, Black or African American: 13.3% vs 12.5%, Asian: 1.8% vs 5.8%, Hispanic: 14.4% vs 18.5%). We also observed parity in the proportions of males and females between AZ clinical trials and US Census (males: 52.4% vs 49.2%, females: 47.6% vs 50.8%). Comparisons of four distinct therapy areas within AZ (Respiratory and Immunology [R&I]; Cardiovascular, Renal, and Metabolism [CVRM]; Solid Tumors; and Hematological Malignancies), including by trial phases, revealed greater variability, with proportions observed above and below US Census levels. CONCLUSION: This analysis provides the first detailed insights into the representativeness of AZ trials. Overall, the proportions of different race/ethnicity and sex subgroups in AZ-sponsored clinical trials were broadly aligned with the US Census. We outline some of AZ's planned health equity initiatives that are intended to continue to improve equitable patient enrollment.

2023 in review: FDA approvals of new medicines.

An analysis of all new entities approved by both the Center for Drug Evaluation and Research (CDER) and the Center for Biologics Evaluation and Research (CBER) identified the approval of 69 new entities in the year 2023, 50 % more than in the previous year. Oncology drugs tied with congenital and infectious diseases drugs for the most approvals. Although orphan and priority approvals continued at a high pace, the rate of fast-track approvals continued to decline. The rate of industry consolidation also picked up again after decreasing slightly in 2022.

Assessing biologic/toxicologic effects of extractables from plastic contact materials for advanced therapy manufacturing using cell painting assay and cytotoxicity screening.

Plastic components are essential in the pharmaceutical industry, encompassing container closure systems, laboratory handling equipment, and single-use systems. As part of their material qualification process, studies on interactions between plastic contact materials and process solutions or drug products are conducted. The assessment of single-use systems includes their potential impact on patient safety, product quality, and process performance. This is particularly crucial in cell and gene therapy applications since interactions with the plastic contact material may result in an adverse effect on the isolated therapeutic human cells. We utilized the cell painting assay (CPA), a non-targeted method, for profiling the morphological characteristics of U2OS human osteosarcoma cells in contact with chemicals related to plastic contact materials. Specifically, we conducted a comprehensive analysis of 45 common plastic extractables, and two extracts from single-use systems. Results of the CPA are compared with a standard cytotoxicity assay, an osteogenesis differentiation assay, and in silico toxicity predictions. The findings of this feasibility study demonstrate that the device extracts and most of the tested compounds do not evoke any measurable biological changes on the cells (induction ≤ 5%) among the 579 cell features measured at concentrations ≤ 50 µM. CPA can serve as an important assay to reveal unique information not accessible through quantitative structure-activity relationship analysis and vice versa. The results highlight the need for a combination of in vitro and in silico methods in a comprehensive assessment of single-use equipment utilized in advanced therapy medicinal products manufacturing.

Financial conflicts of interest among presenters, panellists and moderators at haematology and oncology FDA workshops.

OBJECTIVE: To assess the characteristics and financial conflicts of interest of presenters, panellists and moderators at haematology and oncology workshops held jointly with or hosted by the US FDA. SETTING: We included information on all publicly available haematology or oncology FDA workshop agendas held between 1 January 2018 and 31 December 2022. EXPOSURE: General and research payments reported on Open Payments, industry funding to patient advocacy organizations reported on their webpages or 990 tax forms and employment in both pharmaceutical and regulatory settings. RESULTS: Among physicians eligible for payments, 78% received at least one payment from the industry between 2017 and 2021. The mean general payment amount was $82,170 for all years ($16,434 per year) and the median was $14,906 for all years ($2981 per year). Sixty-nine per cent of patient advocacy speakers were representing organizations that received financial support from the pharmaceutical industry. Among those representing regulatory agencies or pharmaceutical companies, 16% had worked in both settings during their careers. CONCLUSIONS AND RELEVANCE: Our findings in this cross-sectional study show a majority of US-based physician presenters at haematology and oncology workshops held jointly with members of the US FDA have some financial conflict of interest with the pharmaceutical industry. These findings support the need for clear disclosures and suggest that a more balanced selection of presenters with fewer conflicts may help to limit bias in discussions between multiple stakeholders.

Next-generation hybrid technologies for the treatment of pharmaceutical industry effluents.

Water and industries are intangible units of the globe that are always set to meet the population's demand. The global population depends on one-third of freshwater increasing the demand. The increase in population along with urbanization has polluted the fresh water resources. The pharmaceutical industry is marked as an emerging contaminant of water pollution. The most common type of pharmaceutical drugs that are detected in the environment includes antibiotics, analgesics, NSAIDs, and pain-relieving drugs. These drugs alter the food chain of the organisms causing chaos mainly in the marine ecosystem. Pharmaceutical drugs are found only in shallow amounts (ng/mg) they have a huge impact on the living system. The consumption of water contaminated with pharmaceutical ingredients can disrupt reproduction, hormonal imbalance, cancer, and respiratory problems. Various methods are used to remove these chemicals from the environment. In this review, we mainly focused on the emerging hybrid technologies and their significance in the effective treatment of pharmaceutical wastewater. This review paper primarily elaborates on the merits and demerits of existing conventional technologies helpful in developing integrated technologies for the modern era of pharmaceutical effluent treatment. This review paper further in detail discusses the various strategies of eco-friendly bioremediation techniques namely biostimulation, bioaugmentation, bacterial degradation, mycoremediation, phytoremediation, and others for the ultimate removal of pharmaceutical contaminants in wastewater. The review makes clear that targeted and hybrid solutions are what the world will require in the future to get rid of these pharmacological prints.

The Pharmaceutical Industry in 2023: An Analysis of FDA Drug Approvals from the Perspective of Molecules.

With the COVID-19 pandemic behind us, the U.S. Food and Drug Administration (FDA) has approved 55 new drugs in 2023, a figure consistent with the number authorized in the last five years (53 per year on average). Thus, 2023 marks the second-best yearly FDA harvest after 2018 (59 approvals) in all the series. Monoclonal antibodies (mAbs) continue to be the class of drugs with the most approvals, with an exceptional 12, a number that makes it the most outstanding year for this class. As in 2022, five proteins/enzymes have been approved in 2023. However, no antibody-drug conjugates (ADCs) have been released onto the market. With respect to TIDES (peptides and oligonucleotides), 2023 has proved a spectacular year, with a total of nine approvals, corresponding to five peptides and four oligonucleotides. Natural products continue to be the best source of inspiration for drug development, with 10 new products on the market. Three drugs in this year's harvest are pegylated, which may indicate the return of pegylation as a method to increase the half-lives of drugs after the withdrawal of peginesatide from the market in 2013. Following the trends in recent years, two bispecific drugs have been authorized in 2023. As in the preceding years, fluorine and/or N-aromatic heterocycles are present in most of the drugs. Herein, the 55 new drugs approved by the FDA in 2023 are analyzed exclusively on the basis of their chemical structure. They are classified as the following: biologics (antibodies, proteins/enzymes); TIDES (peptide and oligonucleotides); combined drugs; pegylated drugs; natural products; nitrogen aromatic heterocycles; fluorine-containing molecules; and other small molecules.

In-lab synthesized turn-off fluorescence sensor for estimation of Gemigliptin and Rosuvastatin polypill appraised by Spider diagram, AGREE and whiteness metrics.

Gemigliptin-Rosuvastatin single-pill combination is a promising therapeutic tool in the effective control of hyperglycemia and hypercholesterolemia. Organic sensors with high quantum yields have profoundly significant applications in the pharmaceutical industry, such as routine quality control of marketed formulations. Herein, the fluorescence sensor, 2-Morpholino-4,6-dimethyl nicotinonitrile 3, (λex; 226 nm, λem; 406 nm), was synthesized with a fluorescence quantum yield of 56.86% and fully characterized in our laboratory. This sensor showed high efficiency for the determination of Gemigliptin (GEM) and Rosuvastatin (RSV) traces through their stoichiometric interactions and simultaneously fractionated by selective solvation. The interaction between the stated analytes and sensor 3 was a quenching effect. Various experimental parameters and the turn-off mechanism were addressed. The adopted approach fulfilled the ICH validation criteria and showed linear satisfactory ranges, 0.2-2 and 0.1-1 µg/mL for GEM and RSV, respectively with nano-limits of detection less than 30 ng/mL for both analytes. The synthesized sensor has been successfully applied for GEM and RSV co-assessment in their synthetic polypill with excellent % recoveries of 98.83 ± 0.86 and 100.19 ± 0.64, respectively. No statistically significant difference between the results of the proposed and reported spectrophotometric methods in terms of the F- and t-tests. Ecological and whiteness appraisals of the proposed study were conducted via three novel approaches: the Greenness Index via Spider Diagram, the Analytical Greenness Metric, and the Red-Green-Blue 12 model. The aforementioned metrics proved the superiority of the adopted approach over the previously published one regarding eco-friendliness and sustainability. Our devised fluorimetric turn-off sensing method showed high sensitivity, selectivity, feasibility, and rapidity with minimal cost and environmental burden over other sophisticated techniques, making it reliable in quality control labs.

Development of an effective cleaning technique and ancillary analytical method for estimation of residues of selected kinase inhibitors from stainless steel and glass surfaces by swab sampling.

Importance of cleaning validation in the pharmaceutical industry cannot be overstated. It is essential for preventing cross-contamination, ensuring product quality & safety, and upholding regulatory standards. The present study involved development of an effective cleaning method for five selected kinase inhibitors binimetinib (BMT), selumetinib (SMT), brigatinib (BGT), capmatinib (CPT), and baricitinib (BRT). For checking the effectiveness of the developed cleaning technique, a sensitive and specific RP-HPLC based analytical method employing a diode array detector has been established to quantitate drug residue on glass and stainless steel surfaces. A reproducible swab sampling protocol utilizing TX714A Alpha swabs wetted with an extracting solvent has been developed to collect representative samples from both surfaces. Chromatographic separation of selected kinase inhibitors was achieved in gradient mode using an Agilent Zorbax eclipsed C18 column with acetonitrile and 10 mM ammonium formate as the mobile phase. The analytes were chromatographically separated in a 12 min run time. The mean swab recovery for each drug from glass and stainless steel surfaces exceeded 90%. Cleaning with IPA (70%) and acetone (70%) effectively removed residues for all five drugs. A solution comprising 10 mM SDS with 20% IPA demonstrated good efficacy in cleaning residues of BGT, BRT, and CPT, but exhibited lower efficacy for SMT and BMT.

Antibody-Drug Conjugate Overview: a State-of-the-art Manufacturing Process and Control Strategy.

Antibody-drug conjugates (ADCs) comprise an antibody, linker, and drug, which direct their highly potent small molecule drugs to target tumor cells via specific binding between the antibody and surface antigens. The antibody, linker, and drug should be properly designed or selected to achieve the desired efficacy while minimizing off-target toxicity. With a unique and complex structure, there is inherent heterogeneity introduced by product-related variations and the manufacturing process. Here this review primarily covers recent key advances in ADC history, clinical development status, molecule design, manufacturing processes, and quality control. The manufacturing process, especially the conjugation process, should be carefully developed, characterized, validated, and controlled throughout its lifecycle. Quality control is another key element to ensure product quality and patient safety. A patient-centric strategy has been well recognized and adopted by the pharmaceutical industry for therapeutic proteins, and has been successfully implemented for ADCs as well, to ensure that ADC products maintain their quality until the end of their shelf life. Deep product understanding and process knowledge defines attribute testing strategies (ATS). Quality by design (QbD) is a powerful approach for process and product development, and for defining an overall control strategy. Finally, we summarize the current challenges on ADC development and provide some perspectives that may help to give related directions and trigger more cross-functional research to surmount those challenges.

Threaten, Distract, and Discredit: Cannabis Industry Rhetoric to Defeat Regulation of High-THC Cannabis Products in Washington State.

OBJECTIVE: Washington State legislators have attempted to regulate high delta-9-tetrahydrocannabinol (THC) cannabis to reduce cannabis-related harms. Historically, industry actors of other health-compromising products have influenced governments' adoption of evidence-based regulation policies. A better understanding of the industry rhetoric can be used by public health advocates to develop counterarguments and disseminate alternative narratives that protect the public's health. We analyzed the arguments used by cannabis industry actors opposing regulations to de-incentivize the availability and use of high-THC products in Washington State. METHOD: We analyzed 41 testimonies transcribed from 33 cannabis industry actors in 3 public bill hearings and one legislative work session that occurred between 2020 and 2023. Using a deductive thematic analysis, informed by industry actors' arguments opposing regulation of alcohol, tobacco, and high-sugar beverages, we developed a codebook to analyze and identify themes within cannabis industry rhetorical strategies. RESULTS: We identified three main rhetorical strategies used by cannabis industry actors to oppose THC content regulation: threaten, distract, discredit. The most frequently used rhetorical strategy was threats to economic benefits, public health, and the will of the people. The other two most apparent strategies were distracting from the bill's focus by introducing a tangential topic and discrediting the science that supported regulation of cannabis products with high THC concentration or its advocates. CONCLUSIONS: Cannabis industry actors have leveraged several arguments used by industry actors of other health-compromising products to undermine initiatives to advance public health. They have also adapted rhetoric from other industries to the unique conditions of the cannabis regulatory landscape.

Comamonas resistens sp. nov. and Pseudomonas triclosanedens sp. nov., two members of the phylum Pseudomonadota isolated from the wastewater treatment system of a pharmaceutical factory.

Five strains of two novel species were isolated from the wastewater treatment systems of a pharmaceutical factory located in Zhejiang province, PR China. Strains ZM22T and Y6 were identified as belonging to a potential novel species of the genus Comamonas, whereas strains ZM23T, ZM24 and ZM25 were identified as belonging to a novel species of the genus Pseudomonas. These strains were characterized by polyphasic approaches including 16S rRNA gene analysis, multi-locus sequence analysis, average nucleotide identity (ANI), in silico DNA-DNA hybridization (isDDH), physiological and biochemical tests, as well as chemotaxonomic analysis. Genome-based phylogenetic analysis further confirmed that strains ZM22T and Y6 form a distinct clade closely related to Comamonas testosteroni ATCC 11996T and Comamonas thiooxydans DSM 17888T. Strains ZM23T, ZM24 and ZM25 were grouped as a separate clade closely related to Pseudomonas nitroreducens DSM 14399T and Pseudomonas nicosulfuronedens LAM1902T. The orthoANI and isDDH results indicated that strains ZM22T and Y6 belong to the same species. In addition, genomic DNA fingerprinting demonstrated that these strains do not originate from a single clone. The same results were observed for strains ZM23T, ZM24 and ZM25. Strains ZM22T and Y6 were resistant to multiple antibiotics, whereas strains ZM23T, ZM24 and ZM25 were able to degrade an emerging pollutant, triclosan. The phylogenetic, physiological and biochemical characteristics, as well as chemotaxonomy, allowed these strains to be distinguished from their genus, and we therefore propose the names Comamonas resistens sp. nov. (type strain ZM22=MCCC 1K08496T=KCTC 82561T) and Pseudomonas triclosanedens sp. nov. (type strain ZM23T=MCCC 1K08497T=JCM 36056T), respectively.

Drug development for major chronic health conditions-aligning with growing public health needs: Proceedings from a multistakeholder think tank.

The global pharmaceutical industry portfolio is skewed towards cancer and rare diseases due to more predictable development pathways and financial incentives. In contrast, drug development for major chronic health conditions that are responsible for a large part of mortality and disability worldwide is stalled. To examine the processes of novel drug development for common chronic health conditions, a multistakeholder Think Tank meeting, including thought leaders from academia, clinical practice, non-profit healthcare organizations, the pharmaceutical industry, the Food and Drug Administration (FDA), payors as well as investors, was convened in July 2022. Herein, we summarize the proceedings of this meeting, including an overview of the current state of drug development for chronic health conditions and key barriers that were identified. Six major action items were formulated to accelerate drug development for chronic diseases, with a focus on improving the efficiency of clinical trials and rapid implementation of evidence into clinical practice.

A comprehensive review of biosurfactant production and its uses in the pharmaceutical industry.

Biosurfactants are naturally occurring, surface-active chemicals generated by microorganisms and have attracted interest recently because of their numerous industrial uses. Compared to their chemical equivalents, they exhibit qualities that include lower toxic levels, increased biodegradable properties, and unique physiochemical properties. Due to these traits, biosurfactants have become attractive substitutes for synthetic surfactants in the pharmaceutical industry. In-depth research has been done in the last few decades, demonstrating their vast use in various industries. This review article includes a thorough description of the various types of biosurfactants and their production processes. The production process discussed here is from oil-contaminated waste, agro-industrial waste, dairy, and sugar industry waste, and also how biosurfactants can be produced from animal fat. Various purification methods such as ultrafiltration, liquid-liquid extraction, acid precipitation, foam fraction, and adsorption are required to acquire a purified product, which is necessary in the pharmaceutical industry, are also discussed here. Alternative ways for large-scale production of biosurfactants using different statistical experimental designs such as CCD, ANN, and RSM are described here. Several uses of biosurfactants, including drug delivery systems, antibacterial and antifungal agents, wound healing, and cancer therapy, are discussed. Additionally, in this review, the future challenges and aspects of biosurfactant utilization in the pharmaceutical industry and how to overcome them are also discussed.

Non-mutagenic impurities - Recent industry experience of using dose durational limits in drug development.

Absence of clear guidance on the qualification threshold for non-mutagenic impurities during clinical development is a source of inconsistency in both sponsor qualification approaches and health authority requests. A survey was conducted in March 2020 with 6 member companies of the European Federation of Pharmaceutical Industries and Associations (EFPIA). Thirteen examples were gathered of where non-International Council for Harmonisation (ICH) limits have been used in regulatory submissions for various indications and stages of development, together with the regulatory outcomes. As expected, few challenges were faced in early clinical development, with health authorities generally commenting that sponsors should work towards ICH Q3A and Q3B guideline specification limits as development progresses. However, inconsistent health authority requests were noted even for early phase clinical trials in late-stage oncology patients. For an optimised use of resources, consistent approaches would have the benefit of supporting faster access of safe medicines to patients while including Replacement, Reduction and Refinement (the 3Rs) considerations with respect to animal testing.

Associations between pharmaceutical industry payments to physicians and prescription of PARP inhibitors in the United States.

PURPOSE: To evaluate the association between industry payments to physicians related to poly (ADP-ribose) polymerase inhibitors (PARPis) and physicians' prescribing behaviors for PARPis. METHODS: This panel-data analysis used the publicly accessible Open Payments Database and Medicare Part D database between 2017 and 2021. All physicians who reported >10 claims for either olaparib, rucaparib, or niraparib were included in this study. Non-research payments for the PARPis to the physicians from the PARPi manufacturers were extracted from the Open Payments Database. Associations between the physicians' receipt of payments and likelihood of prescribing PARPis were assessed with logistic generalized estimating equations (GEEs). Dose-response associations between the number of payments and prescription volumes and Medicare expenditures were evaluated with linear GEEs. RESULTS: Of the 1686 eligible physician prescribers, 68.7% received one or more non-research payments related to any of the three PARPis from the manufacturers between 2017 and 2021. Median annual payments per physician were $57 for olaparib, $39 for rucaparib, and $62 for niraparib. Receipt of payments for each PARPi was associated with higher odds of prescribing olaparib (odds ratio [OR]: 1.30 [95% CI: 1.14-1.48], p < 0.001), rucaparib (OR: 2.07 [95% CI: 1.58-2.72], p < 0.001), and niraparib (OR: 1.49 [95% CI: 1.22-1.81], p < 0.001). Dose-response effects were observed between the number of annual payments and the number of prescriptions and/or Medicare expenditures for olaparib and rucaparib. CONCLUSION: Non-research payments to physician prescribers of PARP inhibitors from the manufacturers were significantly associated with increased prescriptions and Medicare expenditures for olaparib and rucaparib in the United States.

Lessons from assembling a microbial natural product and pre-fractionated extract library in an academic laboratory.

Microbial natural products are specialized metabolites that are sources of many bioactive compounds including antibiotics, antifungals, antiparasitics, anticancer agents, and probes of biology. The assembly of libraries of producers of natural products has traditionally been the province of the pharmaceutical industry. This sector has gathered significant historical collections of bacteria and fungi to identify new drug leads with outstanding outcomes-upwards of 60% of drug scaffolds originate from such libraries. Despite this success, the repeated rediscovery of known compounds and the resultant diminishing chemical novelty contributed to a pivot from this source of bioactive compounds toward more tractable synthetic compounds in the drug industry. The advent of advanced mass spectrometry tools, along with rapid whole genome sequencing and in silico identification of biosynthetic gene clusters that encode the machinery necessary for the synthesis of specialized metabolites, offers the opportunity to revisit microbial natural product libraries with renewed vigor. Assembling a suitable library of microbes and extracts for screening requires the investment of resources and the development of methods that have customarily been the proprietary purview of large pharmaceutical companies. Here, we report a perspective on our efforts to assemble a library of natural product-producing microbes and the establishment of methods to extract and fractionate bioactive compounds using resources available to most academic labs. We validate the library and approach through a series of screens for antimicrobial and cytotoxic agents. This work serves as a blueprint for establishing libraries of microbial natural product producers and bioactive extract fractions suitable for screens of bioactive compounds. ONE-SENTENCE SUMMARY: Natural products are key to discovery of novel antimicrobial agents: Here, we describe our experience and lessons learned in constructing a microbial natural product and pre-fractionated extract library.