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Policy makers and insurers promote the use of generic drugs because they can deliver large savings without sacrificing quality. But these efforts meet resistance from the public, who perceive generic drugs as inferior substitutes for brand name counterparts. Building on literature showing that negative emotions reduce risk-taking, the authors hypothesize that receiving bad medical news (i.e., negative information about one's health) prompts patients to favor brand name over generic drugs as means to safeguard their health. The evidence exploits low-density lipoprotein cholesterol test results, where a discontinuity from clinical guidelines enables the authors to estimate the causal effect of bad medical news. Using data covering patients' prescription drug choices across drug classes, the authors find that patients receiving bad medical news become 8% more likely to choose the brand name alternative. The findings are reinforced by a secondary analysis incorporating the similar context of hemoglobin A1c (blood sugar) testing. The authors also find that bad medical news reduces preferences for generics most strongly among drugs of direct clinical relevance for each test, but the effect also manifests among non–clinically relevant drugs. [ABSTRACT FROM AUTHOR]

Repurposing generic drugs as new treatments for life-threatening diseases such as cancer is an exciting yet largely overlooked opportunity due to a lack of market-driven incentives. Nonprofit organizations and other non-manufacturers have been ramping up efforts to repurpose widely available generic drugs and rapidly expand affordable treatment options for patients. However, these nonmanufacturers find it difficult to obtain regulatory approval in the U.S. Without a straightforward path for approval and updating drug labeling, non-manufacturers have relied on off-label use of repurposed drugs. This limits the broad clinical adoption of these drugs and patient access. In this paper, we explore the regulatory landscape for repurposing of small molecule generic drugs within the U.S. We describe case studies of repurposed drugs that have been successfully incorporated into clinical treatment guidelines for cancer without regulatory approval. To encourage greater adoption of generic drugs in clinical practice-that is, to encourage the repurposing of these drugs-we examine existing Food and Drug Administration (FDA) pathways for approval of new uses or indications for generic drugs. We show how non-manufacturers, who are generally more active in generic drug repurposing than manufacturers, could utilize existing regulatory authorities and pathways, and we describe the challenges they face. We propose an extension of the existing 505(b)(2) new drug application (NDA) approval pathway, called a "labeling-only" 505(b)(2) NDA, that would enable non-manufacturers to seek approval of new indications for well-established small molecule drugs when multiple generic products are already available. It would not require new chemistry, manufacturing, and controls (CMC) data or introducing new drug products into the marketplace. This pathway would unlock innovation broadly and enable patients to benefit from the enormous potential of low-cost generic drugs. [ABSTRACT FROM AUTHOR]

ABSTRACT A three‐arm comparative clinical endpoint bioequivalence (BE) study is often used to establish bioequivalence (BE) between a locally acting generic drug (T) and reference drug (R), where superiority needs to be established for T and R over Placebo (P) and equivalence needs to be established for T vs. R. Sometimes, when study design parameters are uncertain, a fixed design study may be under‐ or over‐powered and result in study failure or unnecessary cost. In this paper, we propose a two‐stage adaptive clinical endpoint BE study with unblinded sample size re‐estimation, standard or maximum combination method, optimized allocation ratio, optional re‐estimation of the effect size based on likelihood estimation, and optional re‐estimation of the R and P treatment means at interim analysis, which have not been done previously. Our proposed method guarantees control of Type 1 error rate analytically. It helps to reduce the average sample size when the original fixed design is overpowered and increases the sample size and power when the original study and group sequential design are under‐powered. Our proposed adaptive design can help generic drug sponsors cut cost and improve success rate, making clinical study endpoint BE studies more affordable and more generic drugs accessible to the public. [ABSTRACT FROM AUTHOR]

This study was conducted as a single‐site, open‐label, randomized, replicated crossover trial with 4 treatment periods. The aim was to evaluate the bioequivalence of a generic test drug containing velpatasvir and sofosbuvir compared to an established brand‐name medication in healthy White subjects under fasting conditions. Blood samples were collected at specified intervals up to 72 hours after dosing to measure the concentrations of velpatasvir and sofosbuvir using a certified high‐performance liquid chromatography with tandem mass spectrometry method. The bioequivalence of the 2 formulations was confirmed when statistical analysis showed that confidence intervals for the log‐transformed peak concentration and area under the concentration‐time curve from time 0 to the last quantifiable sample were within an acceptable range from 80% to 125%. Criteria for bioequivalence were met for both area under the concentration‐time curve from time 0 until the last quantifiable sample and peak concentration parameters. No adverse effects were reported during this trial in both groups. [ABSTRACT FROM AUTHOR]

By September 2024, the Centers for Medicare and Medicaid Services (CMS) will publicly report the negotiated prices (Maximum Fair Prices) for the first 10 drugs selected for price negotiation. We estimate initial price offers based on net prices, statutorily defined ceilings, and comparative effectiveness data for the 10 drugs and their therapeutic alternatives. We utilized net prices and other price benchmarks for the 10 drugs and their therapeutic alternatives. We searched for data on comparative clinical effectiveness for the primary indications. We outlined a range of plausible initial price offers based on CMS guidance and our interpretation of regulatory intent. For ibrutinib and ustekinumab, statutorily defined ceiling prices will likely determine the initial price offers. The integration of net pricing and clinical evidence from comparator branded products will inform the initial price offers for apixaban, empagliflozin, etanercept, and insulin aspart. Rivaroxaban and sacubitril/valsartan have therapeutic alternatives that are generics; therefore, CMS may apply a discount to current net prices. To achieve savings in the negotiation of dapagliflozin and sitagliptin, CMS will have to leverage additional negotiation factors because statutory defined ceilings and net prices of therapeutic alternatives are similar or higher. This analysis sheds light on important price benchmarks and clinical evidence factors for the determination of the initial price offers. Although we were not able to simulate the offer and counter-offer process, our findings provide a transparent and systematic way to produce initial offers that are consistent with CMS guidance. • The Centers for Medicare and Medicaid Services will publicly report the negotiated prices (Maximum Fair Prices) for the first 10 drugs selected for price negotiation. • We report an estimate of the initial price offers to inform negotiation. • This analysis sheds light on important price benchmarks and the integration of comparative clinical evidence for the determination of the initial price offers. [ABSTRACT FROM AUTHOR]

The COVID-19 global pandemic, over the last year and a half, has managed to create massive disruptions in global supply chains and exposed their vulnerabilities, thereby reemphasizing the importance of resiliency. The current study aims to identify and prioritize, through the quantitative decision-making technique of Interpretive Structural Modelling (ISM), a set of barriers to resiliency for the pharmaceutical supply chain in India. The rationale behind choosing the Indian pharmaceutical supply chain was that the pharmaceutical sector in India supplies over half of the global demand for vaccines and generic drugs, and the trajectory of growth is indicated around US$100 billion by the year 2025, along with exporting pharmaceutical products to nearly 200 destination countries. The findings of the current study are expected to aid the decision-makers in evaluating the relative criticality and the interrelationship between the potential (and critical) barriers to supply chain resiliency, and in turn to develop strategic plans. This, in turn, can help to combat unforeseen supply chain disruptors such as COVID-19. This methodology and the findings of the study can be generalized for other supply chains. [ABSTRACT FROM AUTHOR]

Background: Decision-makers in middle-income countries need evidence on the cost-effectiveness of COVID-19 booster doses and oral antivirals to appropriately prioritise these healthcare interventions. Methods: We used a dynamic transmission model to assess the cost-effectiveness of COVID-19 booster doses and oral antivirals in Fiji, Indonesia, Papua New Guinea, and Timor-Leste. We conducted cost-effectiveness analysis from both healthcare and societal perspectives using data collated from publicly available sources. We developed an interactive R Shiny which allows the user to vary key model assumptions, such as the choice of discounting rate, and view how these assumptions affect model results. Findings: Booster doses were cost saving and therefore cost-effective in all four middle-income settings from both healthcare and societal perspectives using 3% discounting. Providing oral antivirals was cost-effective from a healthcare perspective if procured at a low generic price (US$25) or middle-income reference price (US$250); however, their cost-effectiveness was strongly influenced by rates of wastage or misuse, and the ongoing costs of care for patients hospitalised with COVID-19. The cost or wastage of rapid antigen tests did not appear strongly influential over the cost-effectiveness of oral antivirals in any of the four study settings. Conclusions: Our results support that COVID-19 booster programs are cost-effective in middle-income settings. Oral antivirals demonstrate the potential to be cost-effective if procured at or below a middle-income reference price of US$250 per schedule. Further research should quantify the rates of wastage or misuse of oral COVID-19 antivirals in middle-income settings. [ABSTRACT FROM AUTHOR]

This document contains summaries of various research studies in the field of pharmacology and drug development. The studies cover a range of topics, including pharmacokinetic modeling, drug distribution, safety, dosing recommendations, cardiac safety, and the relationship between zinc deficiency and liver damage. The summaries provide concise and factual information about the studies, highlighting their key findings and implications. The document aims to provide library patrons with a quick overview of the research studies, allowing them to determine if they want to explore the full text further. The summaries are culturally sensitive and respectful of diverse perspectives, presenting the information objectively without adopting any judgments or biases. This document contains summaries of various research studies related to pharmacokinetics and drug interactions. The studies cover a range of topics, including the safety and efficacy of different medications, the impact of drug-drug interactions on exposure, and the demographic representation in clinical trials. The findings provide valuable insights into the pharmacokinetics of these drugs, potential drug interactions, and the need for diversity in clinical trial populations. Overall, these studies contribute to our understanding of drug safety and optimization of dosing regimens. [Extracted from the article]

Introduction: Prescription patterns significantly impact healthcare quality and patient outcomes. Evaluating these patterns using World Health Organisation (WHO) indicators helps identify areas for improvement and ensures rational drug use. The present study was conducted to evaluate prescription patterns via WHO indicators, aiming to uncover insights, identify discrepancies and enhance prescription quality within the institute for improved healthcare outcomes. Aim: To evaluate drug prescription patterns using WHO prescription indicators in the prescriptions of outdoor patients at a tertiary care teaching hospital in Chhattisgarh, India. Materials and Methods: A cross-sectional study was conducted in the Department of Pharmacology at Department of Pharmacology, Pt. J.N.M. Medical College, Raipur, Chhattisgarh, India, from July 15, 2023, to October 15, 2023 (a duration of 3 months), involving 1,000 outpatient prescriptions at Dr. Bhimrao Ambedkar Memorial Hospital (BRAM), Raipur, Chhattisgarh. Ethical clearance was obtained from the Institutional Ethics Committee (IEC) (No./MCI/Ethics/2023/45 Raipur, dated 12/07/2023). Data were collected using a digital form and analysed statistically. Parameters evaluated included the average number of medicines per prescription, the percentage of drugs prescribed by generic name, the percentage of prescriptions containing antibiotics, the percentage of prescriptions containing injections, and the percentage of drugs prescribed from the Essential Drug List (EDL). Descriptive statistics were used to summarise the data, and analysis was performed using Microsoft (MS) Excel 2021. Results: The present study included 1,000 prescriptions. A total of 4,320 medicines were prescribed across these prescriptions, with 2,853 (66.04%) prescribed by their generic name. Injections accounted for 483 (11.18%) prescriptions, while antibiotics were included in 663 (15.34%) prescriptions. Additionally, 2,973 (68.81%) medicines were prescribed from the EDL. The average number of medicines prescribed per prescription was 4.3. Conclusion: The study revealed that while certain aspects of prescription practices aligned with WHO indicators, notable discrepancies persisted. The percentage of antibiotics prescribed per prescription was in accordance with WHO guidelines. Strategic measures are needed to enhance prescription practices and align them more closely with WHO guidelines. [ABSTRACT FROM AUTHOR]

Cancer remains a leading cause of death globally. Cancer patients often seek alternative therapies in addition to, or instead of, conventional treatments like chemotherapy, radiation, and surgery. The progress in medical advancements and early detection provides more treatment options; however, the development of cancer drugs requires a significant amount of time, demands substantial investments, and results in an overall low percent of regulatory approval. The complex relationship between patent protection and pharmaceutical innovation complicates cancer drug development and contributes to high mortality rates. Adjusting patent criteria for alternative cancer therapeutics could stimulate innovation, enhance treatment options, and ultimately improve outcomes for cancer patients. This article explores the potential of alternative cancer therapeutics, chemopreventive agents, natural products, off-patent drugs, generic unpatentable chemicals, and repurposed drugs in cancer treatment, emphasizing the mechanisms and therapeutic potential of these unconventional compounds as combinatorial cancer therapies. The biological pathways, therapeutic effects, and potential to enhance existing therapies are reviewed, demonstrating their cost-effective and accessible options as adjuvant cancer therapies. [ABSTRACT FROM AUTHOR]

Background: The global surge in non-communicable diseases, like cancer, strains health systems financially and restricts patient access to treatment. Generic drugs offer comparable efficacy, safety, and quality to innovator drugs, improving patient access and well-being. To aid healthcare workers in selecting the best generic drugs, Generic drug Adoption Framework (GRAF) was developed as an evaluation tool. This paper aims to adapt the tool to Colombia for healthcare professional's daily use. Methods: Adapting the tool involved two phases: surveying healthcare workers (oncologists' specialists and pharmacists) to gauge their readiness for adopting generic drugs, additionally and expert consensus was developed to adapt the tool to the Colombian context. Results: Of 62 surveyed healthcare workers, 38.7% were early adopters and 32.3% were late adopters. Pharmacists showed higher early adoption rates (47%) than physicians (33%). In the second phase, experts identified 12 relevant attributes for the Colombian scenario, refining descriptions and scoring scales. Conclusion: The study revealed Colombian healthcare workers' perceptions of generic drugs and differences in adoption rates. The adapted tool to the Colombian healthcare context could clarify misconceptions that require diverse strategies to increase the use of generic drugs, aiding in better patient care. [ABSTRACT FROM AUTHOR]

Objective This review paper explores strategies and recommendations for reducing healthcare expenses in the Gulf Cooperation Council (GCC) by understanding physicians' attitudes regarding the utilization of generic medicines. Methods A comprehensive search of seven databases yielded 24 437 titles and abstracts. Using inclusion criteria focusing on physicians' insights into generic prescribing and exclusion criteria, cutting out systematic reviews, case studies, and non-English articles, the review process led to an in-depth analysis of six studies. Results Findings revealed that while physicians generally comprehend terms like "generic", "brand", and "bioequivalence", they face difficulty discussing bioequivalence with patients. Lack of emphasis on generic medicines in medical education and complex patient communication were potential impediments to generic medicine prescribing in the GCC countries. Strategies & Recommendations: Promoting the benefits of generic drugs could support their usage and help decrease healthcare costs. Improving medical education to include a larger focus on generic medications and their benefits, as well as training physicians in effectively communicating bioequivalence concepts to patients, could promote the use of more cost-effective, generic options. Conclusion The review calls for attention to the potential of generic medicine prescribing to reduce healthcare expenses in the GCC. Future research studies should consider broadening the geographical scope to provide global insights into these issues and their possible solutions. [ABSTRACT FROM AUTHOR]

In this monograph, the potential use of methods based on the Biopharmaceutics Classification System (BCS) framework to evaluate the bioequivalence of solid immediate-release (IR) oral dosage forms containing fexofenadine hydrochloride as a substitute for a pharmacokinetic study in human volunteers is investigated. We assessed the solubility, permeability, dissolution, pharmacokinetics, pharmacodynamics, therapeutic index, bioavailability, drug-excipient interaction, and other properties using BCS recommendations from the ICH, FDA and EMA. The findings unequivocally support fexofenadine's classification to BCS Class IV as it is neither highly soluble nor highly permeable. Further impeding the approval of generic equivalents through the BCS-biowaiver pathway is the reference product's inability to release ≥ 85 % of the drug substance within 30 min in pH 1.2 and pH 4.5 media. According to ICH rules, BCS class IV drugs do not qualify for waiving clinical bioequivalence studies based on the BCS, even though fexofenadine has behaved more like a BCS class I/III than a class IV molecule in pharmacokinetic studies to date and has a wide therapeutic index. [ABSTRACT FROM AUTHOR]

Calcium ions (Ca2+) participate in the regulation of cellular apoptosis as a second messenger. Calcium overload, which refers to the abnormal elevation of intracellular Ca2+ concentration, is a factor that can lead to cell death. Here, based on the unique biological effects of Ca2+, hollow mesoporous calcium peroxide nanoparticles (HMCPN) were developed by a facile hydrolysis-precipitation method for drug-free tumor calcicoptosis therapy. The average pore size of the optimized HMCPN17 is 6.4 nm, and the surface area is 81.3 m2/g, which enables HMCPN17 with high drug loading capability. The Ca2+ release from HMCPN17 is much faster at pH 6.8 than that at pH 7.4, which can be ascribed to the acid-triggered conversion of HMCPN17 to Ca2+ and H 2 O 2 , indicating a pH-responsive decomposition behavior of HMCPN17. The high drug loading contents of doxorubicin (DOX) and/or sorafenib (SFN) indicate that HMCPN17 can be employed as a generic drug delivery system (DDS). The in vitro and in vivo results reinforce the high calcicoptosis therapeutic efficacy of tumors by our HMCPN17 without drug loading, which can be attributed to the efficient accumulation in tumors and the ability of H 2 O 2 and Ca2+ production at acidic TME. Our HMCPN17 has broad application prospect for construction of multi-drug-loaded composite nanomaterials with diversified functions for the treatment of tumors. The combination of hollow mesoporous nanomaterials and calcium peroxide nanoparticles has a wide range of applications in the synergistic treatment of tumors. In this study, hollow mesoporous calcium peroxide nanoparticles (HMCPN) were developed based on a simple hydrolysis-precipitation method for tumor calcicoptosis therapy without drug loading. The high drug loading contents of DOX and/or SFN indicate that our HMCPN can serve as a generic DDS. The experimental results demonstrated the high calcicoptosis therapeutic efficacy of HMCPN on tumors even without drug loading. [Display omitted] [ABSTRACT FROM AUTHOR]

Background: Dialysis is a life‐sustaining treatment for patients with advanced kidney failure, but it is extremely burdensome. Despite this, there are very few tools available to assess treatment burden within the dialysis population. Objective: To conduct a scoping review of generic and disease‐specific measures of treatment burden in chronic kidney disease, and assess their suitability for use within the dialysis population. Design: We searched CINAHL, MEDLINE and the Cochrane Library for kidney disease‐specific measures of treatment burden. Studies were initially included if they described the development, validation or use of a treatment burden measure or associated concept (e.g., measures of treatment satisfaction, quality of life, illness intrusiveness, disease burden etc.) in adult patients with chronic kidney disease. We also updated a previous scoping review exploring measures of treatment burden in chronic disease to identify generic treatment burden measures. Results: One‐hundred and two measures of treatment burden or associated concepts were identified. Four direct measures and two indirect measures of treatment burden were assessed, using adapted established criteria, for suitability for use within the dialysis population. The researchers outlined eight key dimensions of treatment burden: medication, financial, administrative, lifestyle, health care, time/travel, dialysis‐specific factors, and health inequality. None of the measures adequately assessed all dimensions of treatment burden. Conclusion: Current measures of treatment burden in dialysis are inadequate to capture the spectrum of issues that matter to patients. There is a need for dialysis‐specific burdens and health inequality to be assessed when exploring treatment burden to advance patient care. [ABSTRACT FROM AUTHOR]

Background: Cephalosporins stand as one of the most frequently prescribed antibiotics for combating infectious diseases. This group has proven to be effective in the treatment of both gram positive and gram negative infections. Analysis of price discrepancies among various brands of oral cephalosporins offers guidance for prescribing cost-effectively, which turns out to be beneficial for both the patient and the prescribing physician. A cost-effective prescribing pattern ensures good patient compliance and better treatment outcome. Aims and Objectives: The objectives of the study were to analyze price variation of various single oral cephalosporin formulations available in the Indian market. Materials and Methods: The prices of oral cephalosporins, produced by different pharmaceutical companies in India, with the same strength, were acquired from the current index of medical specialties, January-April 2023. The cost of generics was obtained from the official website janaushadhi.gov.in. The disparity between the highest and lowest prices of the identical formulation manufactured by different companies, the difference between the maximum and minimum prices of brand-name versus generic versions of the identical formulation, as well as the cost ratio and percentage cost variation, were computed. Results: Total number of brands range from 3 to 79 for various drugs. A large price variation was seen across the different brands. The maximum price variation 521.11% was seen with 100 mg of Cefixime and minimum price variation of 14.13% was seen with 125 mg of cefdinir. Conclusion: With the high variation in prices seen among the different drugs it is important to consider the affordability of the patient before prescribing the drug to ensure completion of the course and better treatment outcome. [ABSTRACT FROM AUTHOR]

These nine steps can help you and your staff reduce the hassle of prior authorizations while empowering patients to be part of the process. [ABSTRACT FROM AUTHOR]

Latuda® is a novel antipsychotic drug for schizophrenia and bipolar depression. A bioequivalence trial was performed to investigate the bioequivalence of Latuda® and its generic drug lurasidone. Two independent trials were carried out, each involving 28 subjects. In the fasting trial, subjects were randomly assigned to two groups (1:1 ratio), receiving either 40 mg of generic lurasidone or Latuda®. After a 7-day washout period, subjects entered the second period with a crossover administration of 40 mg of generic lurasidone or Latuda®. The postprandial study design was similar to that of the fasting study. In the fasting study, the pharmacokinetic (PK) parameter values of generic lurasidone and Latuda® were as follows: the Cmax was 28.84 ± 19.34 ng/ml and 28.22 ± 21.19 ng/ml, respectively; the AUC0-t was 121.39 ± 58.47 h*ng/ml and 118.35 ± 52.24 h*ng/ml, respectively; and the AUC0-∞ was 129.63 ± 63.26 h*ng/ml and 126.59 ± 57.99 h*ng/ml, respectively. The primary pharmacokinetic parameter, Cmax, was assessed for equivalence using reference-scaled average bioequivalence (RSABE), while other parameters (AUC0-t, AUC0-∞) were evaluated using average bioequivalence (ABE). The results indicate that both Cmax and AUC meet the equivalence criteria. In the postprandial study, the PK values of generic lurasidone and Latuda® were as follows: the Cmax was 74.89 ± 32.06 ng/ml and 83.51 ± 33.52 ng/ml, respectively; the AUC0-t was 274.77 ± 103.05 h*ng/ml and 289.26 ± 95.25 h*ng/ml, respectively; and the AUC0-∞ was 302.44 ± 121.60 h*ng/ml and 316.32 ± 109.04 h*ng/ml, respectively. The primary pharmacokinetic parameters (Cmax, AUC0-t, AUC0-∞) were assessed for equivalence using ABE, and both met the equivalence criteria. In the study, lurasidone and Latuda® both exhibited acceptable safety and tolerability. The results displayed that lurasidone and Latuda® were bioequivalent and safe in healthy Chinese participants. Clinical Trial Registry: This trial is registered at chinadrugtrials.org.cn (no.: CTR20191717, date: 2019.08.29). [ABSTRACT FROM AUTHOR]

This study aimed to evaluate the pharmacokinetics (PKs) and safety of a generic drug, linezolid, compared to those of a reference drug in healthy Chinese subjects under both fasting and fed conditions. This was a randomized, open‐label, 2‐period, 2‐sequence crossover study. The subjects received a single dose of the test or reference drug, linezolid (600 mg), in each period. The PK parameters were calculated using a non‐compartmental method and compared between the 2 drugs. Bioequivalence was analyzed using geometric mean ratios (GMRs) of the 2 formulations and their corresponding 90% confidence intervals (CIs). The safety of the 2 formulations was assessed under both fasting and fed conditions. Forty‐eight subjects completed the study, 24 each in the fasting and feeding groups. The average plasma concentration‐time patterns of linezolid were similar for both medications under both conditions. The GMR and 90% CIs of the maximum plasma concentration and the area under the plasma concentration‐time curve of linezolid were ranged from 0.80 to 1.25. Both drugs were well tolerated with a similar incidence of adverse drug reactions. In conclusion, the PK and safety profiles of the 2 formulations were comparable. Food intake did not influence the PK profiles of linezolid. These results suggest that the test drug can be used as an alternative to reference drugs. [ABSTRACT FROM AUTHOR]

In Brazil, the judicialization of public health for access to medications has resulted in significant challenges to the management of public policies, especially at the municipal level. To evaluate the profile of drug litigations against the Campinas municipal health system from 2017 to 2021, this study analyzed the characteristics of litigants, medicine dispensation, and the timing of court decisions. A quantitative, analytical, and comparative cross-sectional study was conducted using data on the dispensation of 506 types of medications and 493 court cases. The analysis included sociodemographic, procedural, medical–sanitary, and pharmaceutical assistance management variables. The time of court decisions was assessed using the Kruskal‒Wallis test complemented by the Dunn test. The plaintiffs were predominantly adults, females, and self-declared students, and some cases involved nonresidents. Most of the lawsuits were represented by private lawyers, gratuitousness of justice and with decisions favorable to the plaintiff. However, only 43% of the patients obtained a preliminary injunction or early tutelage. The median time needed for a court decision from the date of case filing was 12 days until the granting of a preliminary injunction or early tutelage and 6.5 months until a judgment or dismissal without a decision on the merits. Approximately 32.4% of the medications dispensed by the judicial pharmacy already belonged to the list of the Brazil's Unified Health System in 2020; 46.3% were prescribed by their generic name; 75.5% had therapeutic equivalents, and 94.9% had marketing authorization from the Brazilian National Health Surveillance Agency. Judicialization in Campinas is an alternative way of accessing medications, but it is time-consuming and benefits only a small portion of the population (0.068%). The characteristics of the plaintiffs and judicialized medicines highlight the need to review health policies to promote equitable and efficient access to essential treatments for the population. [ABSTRACT FROM AUTHOR]

Background. This study aims to assess and explore the different effects of national centralized drug procurement (NCDP) on three targeted antitumor drugs' use in clinical practice. Materials and Methods. Clinical drug volume data were collected covering 18 months before, during, and after the seventh round of the NCDP in Inner Mongolia. The interrupted time‐series method was employed to estimate the net effect of policy impact. Results. The volume of generic afatinib (30 mg) increased by 25.78 DDDs, the expenditures decreased by 3641.14 yuan (p = 0.001), and the DDDc decreased by 124.35 yuan (p < 0.001). The volume of generic afatinib (40 mg) increased by 65.19 DDDs (p < 0.001), the expenditures increased by 1304.93 yuan (p < 0.001), and the DDDc decreased by 120.2 yuan (p < 0.001). The volume of generic sunitinib increased by 75.79 DDDs (p < 0.001), the expenditures decreased by 15869.78 yuan (p < 0.001), and the DDDc decreased by 243.28 yuan. There was no significant change trend in volume, expenditures, and DDDc of the three original‐targeted drugs after NCDP intervention. Conclusions. After the policy intervention, generic afatinib (40 mg) successfully aligned with the objectives of NCDP by reducing drug costs and enhancing patient affordability; however, the desired outcomes were not achieved for generic afatinib (30 mg) and generic sunitinib. This discrepancy may be attributed to the inherent clinical efficacy and safety profiles of these drugs. Therefore, in implementing NCDP, it is necessary to enhance the clinical efficacy and safety of generic‐targeted antitumor drugs while considering economic efficiency. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To evaluate the differences of clinical efficacy and safety between generic and original apixaban after centralized drug volume-based procurement, so as to provide real-world clinical research evidence for the re-evaluation of domestic generic drugs after marketing, and provide supporting evidence for clinicians and related professionals in drug selection. METHODS: This study was a multicenter, large-sample, real-world retrospective cohort study based on the concept of comparative effect research. Clinical data of adult patients underwent hip or knee replacement or post-operation treated with apixaban were extracted from the information system database of the First Affiliated Hospital of Wannan Medical College, Guangdong Provincial People’ s Hospital, Henan Provincial People’ s Hospital and the First Affiliated Hospital of Xi’ an Jiaotong University from Jan. 1st 2019 to Apr. 1st 2022. Patients were divided into 295 cases in original drug group, 641 cases in generic drug group 1 and 50 cases in generic drug group 2 according to the specific medication. Differences in efficacy related to prothrombin time, international normalized ratio, activated partial thromboplastin time and incidence of venous thromboembolic events (VTE), and differences in safety related to aspartate transaminase (AST), alanine aminotransferase (ALT), urea, blood uric acid and creatinine were compared between two groups. RESULTS: (1) In terms of efficacy, after treatment, differences in prothrombin time, international normalized ratio, activated partial thromboplastin time and VTE incidence among three groups were not statistically significant (P>0. 05). (2) In terms of safety, after treatment, differences in the levels of AST, ALT, urea, blood uric acid and creatinine as well as the incidence of related adverse events among three groups were not statistically significant (P>0. 05). CONCLUSIONS: Generic apixaban is comparable to the original drug in terms of efficacy and safety after centralized drug volume-based procurement. [ABSTRACT FROM AUTHOR]

Generic medications contain the identical active ingredient in the same concentration as their branded counterparts and are administered in the same manner, aiming to deliver comparable efficacy, dosage, and clinical outcomes. Nevertheless, variations in additives and formulation processes, particularly noticeable in topical medications, can influence factors like ease of use and patient adherence. Therefore, in this study, we aimed to compare the rheological attributes of branded and generic injectable ointments, assessing disparities in formulation performance and their impact on patient care. Posterisan® Forte and Hemoporison® ointments were used as the branded and generic versions, respectively, and their viscosity, ductility, and viscoelastic properties were evaluated. Posterisan® Forte showcased enhanced spread ability, maintaining uniform flow characteristics across varying temperatures, whereas Hemoporison® displayed pronounced thixotropic properties and stiffness, suggesting potential benefits for applications necessitating reversible viscosity adjustments and heightened rigidity. Despite sharing identical additives, observable differences in physical characteristics highlight the necessity of understanding formulation traits, which could influence ointment behavior. Alterations in fluidity and viscosity may affect how patients perceive and apply the medication, potentially influencing treatment outcomes and the occurrence of adverse effects. [ABSTRACT FROM AUTHOR]

The invasive tetraploid Cirsium vulgare hybridizes with both Cirsium and Lophiolepis. Its conflicted position in molecular phylogenies, and its peculiar combination of morphological, anatomical, and genomic features that are alternatively shared with representatives of Cirsium or Lophiolepis, strongly suggest its intergeneric hybrid origin.Genetic relationships of C. vulgare (8 samples) with genus Lophiolepis (11 species) and other representatives of genus Cirsium (12 species) were evaluated using restriction site‐associated DNA sequencing (RADseq) and examined using analytical and imaging approaches, such as NeighborNet, Heatmap, and STRUCTURE, to identify nuclear genomes admixture. Estimation of the intensity of spontaneous hybridization within and between Cirsium and Lophiolepis was based on herbarium revisions and published data for all reported hybrids pertinent to taxa currently included in Cirsium or Lophiolepis.The genome of any examined Cirsium species is more similar to C. vulgare than to any Lophiolepis species, and vice versa. The nuclear genome of the tetraploid C. vulgare is composed of two equivalent parts, each attributable either to Lophiolepis or to Cirsium; the organellar RADseq data clustered C. vulgare with the genus Cirsium. Spontaneous hybridization between Cirsium and Lophiolepis is significantly less intensive than within these genera.Our analyses provide compelling evidence that the invasive species C. vulgare has an allotetraploid intergeneric origin, with the maternal parent from Cirsium and the paternal from Lophiolepis. For the purpose of delimiting monophyletic genera, we propose keeping Lophiolepis separate from Cirsium and segregating C. vulgare into the hybridogenous genus Ascalea. [ABSTRACT FROM AUTHOR]

The deformulation stage of original drug products, which includes the quantification of critical excipients, is crucial for the successful development of generic drug products of solid dosage form. Sodium lauryl sulphate (SLS) belongs to the group of critical excipients due to its influence on the bioavailability of drugs, such as metformin. The purpose of this work is to carry out a feasibility study in order to develop a simple, economical, and robust analytical method for the quantification of SLS in metformin-containing tablets after their dissolution in water. Firstly, SLS is extracted with chloroform in acidic conditions, followed by the addition of methylene blue (MB) in order to form a SLS-MB ion pair, which is then measured photometrically at a wavelength of 651 nm. Additionally, interference from matrix components (excipients and APIs) was assessed, and it was found that metformin also forms a blue complex; therefore, this specific extraction method was developed. Other matrix components did not interfere with SLS determination. This method shows a well-estimated precision of 3.3% and accuracy of 5%, a calibration linearity of R2 = 0.99990, and a working range of 0.38 µg/mL to 10 µg/mL of SLS in water. The midpoint of the calibration graph corresponds to the concentration of SLS obtained by dissolving a single tablet in 1 L of water. This method seems appropriate for total SLS determination in tablets and can be applicable for deformulation. [ABSTRACT FROM AUTHOR]

Parallel artificial membrane permeability analysis (PAMPA) is used to determine the permeability of compounds through concentrated negatively charged phospholipid bilayer barriers. We employed MacroFlux (a scaled-up version of PAMPA) to test the permeation rate of terazosin hydrochloride (TH) tablets and predict in vivo bioequivalence. The dissolution profiles and permeability of one reference formulation, and seven generic TH tablets, were compared. The dissolution profiles of these generic tablets were equivalent to that of the reference drug in four different media. However, the flux and the total permeated amount of some generic TH tablets were below the lower limit of the confidence interval of the original acceptance range in MacroFlux, which implied risk in the bioequivalence test in vivo. We further evaluated potential factors responsible for this discrepancy by µFlux, including active pharmaceutical ingredient (API) permeability and excipient prescriptions. The analysis showed that different properties of API were a main factor leading to biological inequivalence in the MacroFlux assay, while excipient prescriptions did not have an impact on bioequivalence risk. These data indicated that the flux assay may be a helpful as an auxiliary method for predicting bioequivalence of generic drugs and analyze the factors responsible for bioequivalence risk. [ABSTRACT FROM AUTHOR]

Escalating insulin prices have prompted public scrutiny of the practices of drug manufacturers, pharmacy benefit managers, health insurers, and pharmacies involved in production and distribution of medications. As a result, a series of policies have been proposed or enacted to improve insulin affordability and foster greater equity in access. These policies have implications for other diabetes and obesity therapeutics. Recent legislation, at both the state and federal level, has capped insulin out-of-pocket payments for some patients. Other legislation has targeted drug manufacturers directly in requiring rebates on drugs with price increases beyond inflation rates, an approach that may restrain price hikes for existing medications. In addition, government negotiation of drug pricing, a contentious issue, has gained traction, with the Inflation Reduction Act of 2022 permitting limited negotiation for certain high expenditure drugs without generic or biosimilar competition, including some insulin products and other diabetes medications. However, concerns persist that this may inadvertently encourage higher launch prices for new medications. Addressing barriers to competition has also been a priority such as through increased enforcement against anticompetitive practices (e.g., "product hopping") and reduced regulatory requirements for biosimilar development and market entry. A novel approach involves public production, exemplified by California's CalRx program, which aims to provide biosimilar insulins at significantly reduced prices. Achieving affordable and equitable access to insulin and other diabetes and obesity medications requires a multifaceted approach, involving state and federal intervention, ongoing policy evaluation and refinement, and critical examination of corporate influences in health care. [ABSTRACT FROM AUTHOR]

Introduction: Today, the approval for a generic topical product includes the presentation of therapeutic equivalence to the originator based on clinical trials. To facilitate this procedure, in 2018 the European Medicines Agency (EMA) published a draft guideline on quality and equivalence of topical products, which includes request parameters regarding the quality of the newly developed generic product and test protocols for the implementation of equivalence tests regarding efficacy. Methods: To date, no data are available on the quality and evidence of the proposed test conditions. In this study, we performed an in vitro penetration test (IVPT) following the terms of the EMA draft guideline on two authorized topical products for which therapeutic equivalence was already proven during the approval process. Results: The complex biometric data processing revealed that in vitro equivalence could not be observed for all skin sections for either originator or generic product. Moreover, the necessity of the negative control proposed in the draft guideline is more than questionable. From the results presented, there were indications that a reduced number of skin donors would be sufficient to achieve statistically significant equivalence in the comparison of all applied formulations. Here, n = 7 donors was proposed instead of n ≥ 12 as the EMA draft guideline demands, decreasing the degree of biodiversity simultaneously. Moreover, a higher number of independent replicates (n > 2) was proposed for proper statistics. Conclusion: This bioequivalence study shows insufficient parameters, which should be discussed together with the EMA draft guideline. Plain Language Summary (PLS): Today in Europe the approval of generic drugs requires clinical trials to present therapeutic equivalence to the originator. To facilitate this time- and cost-intensive process, the European Medicines Agency (EMA) published a draft guideline in 2018 proposing test protocols for carrying out equivalence tests for drugs applied on human skin. Although its publication is over 5 years old, it is still in a draft version; moreover, so far no evidence has been presented on whether the experimental settings in the test protocols can prove equivalence. This study should prove the EMA test protocol for in vitro permeation tests (IVPT) as closely as possible on two authorized topical products for which therapeutic equivalence was already proven during the approval process to determine whether their equivalence could be observed by this pharmacokinetic approach as well. Due to the experimental setup, a penetration test was performed to survey the drug diffusion behavior over the skin cross section instead of the amount of drug which permeates through the skin. To the best of our knowledge, this study is the first work published regarding that topic. Here, bioequivalence of the preparations applied, which were equivalent when they were tested on patients during their approval, was not found overall. We recommend reducing the number of donors and increasing the number of replicates to achieve a higher power for the statistical data evaluation. Moreover, an evaluation of the drug amount at the pharmaceutical place of action should be considered in the EMA guideline. [ABSTRACT FROM AUTHOR]

In vitro-In vivo correlation (IVIVC) is a main focus of the pharmaceutical industry, academia and the regulatory sectors, as this is an effective modelling tool to predict drug product in vivo performance based on in vitro release data and serve as a surrogate for bioequivalence studies, significantly reducing the need for clinical studies. Till now, IVIVCs have not been successfully developed for in situ forming implants due to the significantly different in vitro and in vivo drug release profiles that are typically achieved for these dosage forms. This is not unexpected considering the unique complexity of the drug release mechanisms of these products. Using risperidone in situ forming implants as a model, the current work focuses on: 1) identification of critical attributes of in vitro release testing methods that may contribute to differences in in vitro and in vivo drug release from in situ forming implants; and 2) optimization of the in vitro release method, with the aim of developing Level A IVIVCs for risperidone implants. Dissolution methods based on a novel Teflon shape controlling adapter along with a water non-dissolvable glass fiber membrane (GF/F) instead of a water dissolvable PVA film (named as GF/F-Teflon adapter and PVA-Teflon adapter, respectively), and an in-house fabricated Glass slide adapter were used to investigate the impact of: the surface-to-volume ratio, water uptake ratio, phase separation rate (measured by NMP release in 24 h post injection in vitro or in vivo), and mechanical pressure on the drug release patterns. The surface-to-volume ratio and water uptake were shown to be more critical in vitro release testing method attributes compared to the phase separation rate and mechanical pressure. The Glass slide adapter-based dissolution method, which allowed for the formation of depots with bio-mimicking surface-to-volume ratios and sufficient water uptake, has the ability to generate bio-relevant degradation profiles as well as in vitro release profiles for risperidone implants. For the first time, a Level A IVIVC (rabbit model) has been successfully developed for in situ forming implants. Release data for implant formulations with slightly different PLGA molecular weights (MWs) were used to develop the IVIVC. The predictability of the model passed external validation using the reference listed drug (RLD), Perseris®. IVIVC could not be developed when formulations with different PLGA molar ratios of lactic acid to glycolic acid (L/G) were included. The present work provides a comprehensive understanding of the impact of the testing method attributes on drug release from in situ forming implants, which is a valuable practice for level A IVIVC development. [Display omitted] [ABSTRACT FROM AUTHOR]

The Hatch-Waxman Act of 1984 ushered in a new era of affordable medicine, with 90% of all prescriptions today filled with generic drugs. Hatch-Waxman provided an expedited pathway for generic entry and mandated that the FDA publish up-to-date information on patent information related to non-biologic drugs. That publication is known as the Orange Book. Roughly twenty-five years later, the Biosimilars Act similarly aimed to facilitate the entry of less-expensive versions of biologics, which are more complex drugs made by living systems. Information related to biologics and biosimilars is published in what is known as the Purple Book. Biosimilars, however, have captured less of the biologic market and have reduced prices to a lesser extent than generic non-biologic drugs. To explore the biosimilars system’s shortcomings, this Article uses the case study of insulin drugs, which are popular biologics. Insulin offers a natural experiment, given that these drugs were originally listed in the Orange Book before moving to the Purple Book, in 2020. Comparing the intellectual property data available for insulin in both books reveals the surprising dearth of patent information disclosed in the Purple Book. In fact, despite taking inspiration from the Hatch-Waxman regime, the biosimilars system bears little resemblance to its muse. Indeed, the Purple Book is missing intellectual property data for most biologics. Without this information, biosimilar companies are forced to dance in the dark, running into legal barriers made by the brand’s patents. As a result, biosimilar hopefuls may be deterred or delayed from entering the market. The Article concludes with proposals to improve the regulatory pathway for licensing biosimilars and remedy the lack of patent transparency in the Purple Book. With these reforms, biosimilars are better poised to follow in the footsteps of generic drugs, increasing access to life-saving biologic medicines [ABSTRACT FROM AUTHOR]

Background: Every year millions of patients undergo surgery. The prescribing pattern of medications in patients undergoing surgery may differ based on the hospital setup, profile of the patient, and type of surgical procedure. Hence, the present study is undertaken to know the prescribing pattern of pre-anesthetic, intraoperative, and post-operative agents in surgery and orthopedic department. Aims and Objectives: The aim of this study was to analyze the pattern of pre-anesthetic, intraoperative and post-operative medications used in surgery and orthopedic departments at a tertiary care teaching hospital. Materials and Methods: This cross-sectional, observational study was conducted in the departments of surgery and orthopedic in a tertiary care teaching hospital after taking approval from Institutional Ethics Committee. The details of demographic, clinical data and drugs prescribed during the pre-operative, intraoperative, and post-operative period were recorded in a preformed case record form and analyzed using descriptive statistics. Results: A total of 400 patients prescriptions were collected and analyzed which included 244 patients in orthopedic department and 156 patients in the surgery department. The average number of drugs per encounter was 10.01 and 7.25 in the surgery and orthopedic department, respectively. Preoperatively, the majority of patients received ondansetron (99.5%) followed by glycopyrrolate, midazolam, tramadol, and ranitidine. Surgery was done either under general anesthesia (sodium thiopental and sevoflurane) or local anesthesia (Bupivacaine). Skeletal muscle relaxants used along with general anesthetics included succinylcholine, atracurium, and vecuronium. Postoperatively, antimicrobial agents (AMAs) (831) were most commonly used followed by analgesic agents (368). The majority of AMAs were used from "Watch group" (50%) compared to "Access group" (38.88%) (World Health Organization-Access, Watch, Reserve classification). Conclusion: The present study gives an insight into the use of pre-anesthetic, intraoperative, and post-operative medications in our set-up. Generic medicines are used more which is good as it reduces the cost. Post-operative antimicrobial usage was more from the "Watch group" compared to the "Access group," which is a concern and needs implementation of antibiotic policy. [ABSTRACT FROM AUTHOR]

The article reports on the investigation by the U.S. Congress on the pricing and market protection by drug makers of anti-multiple myeloma agent lenalidomide. Topics mentioned include the impact of the tactics used by drug makers on patients and Medicare, the use of risk evaluation and mitigation strategy, called RevAssist, to prevent generic competition and the factors that influenced the pricing activity of lenalidomide.

Generic drugs seem a promising alternative to decrease healthcare costs. However, on one hand, doctors express reluctance toward this kind of drug, and on the other hand, existing literature remains silent about factors explaining their prescribing behavior. The current study mobilizes the Health Belief Model to offer a better understanding of the factors that hinder the prescription of generic drugs by doctors in terms of benefits, barriers, perceived susceptibility, perceived severity, self-efficacy, and action cues. Twenty-four in-depth interviews were conducted with doctors from different specialties. Projective techniques were used including Chinese portrait, completion test, completion task, and association tests. Data analysis was processed using Sphinx software. The paper offers practical recommendations for health authorities and pharmaceutical firms to better promote generics. Increasing the prescription of generic drugs, compared to branded drugs, may increase patient access to affordable drug treatments, decrease healthcare costs and establish rational utilization of medicines. Generic drugs prescription may consequently play an essential role in improving the quality of life. [ABSTRACT FROM AUTHOR]

In response to the COVID-19 pandemic, jails were advised to reduce facility census, particularly the growing population of those with medical/behavioral health vulnerabilities that increased susceptibility to adverse outcomes. Although jail census decreased across the nation in the initial days to months following pandemic declaration, there are minimal data regarding the health status of those who remained in jail. The current investigation aspired to describe jail census trends before/since the onset of COVID-19 and offer snapshots of temporal changes and context for prevalence estimates of medical/behavioral health conditions in jail detainees from 2019 to 2023. Using a serial cross-sectional design, prescription information for individuals residing in 18 jails across the United States on June 30 of each respective year was extracted and categorized using MediSpan's ontological system to determine prevalence estimates of prescribed agents/products. Although data evidenced an initial 31% census reduction (followed by gradual return to prepandemic rates), prescribing patterns for all major therapeutic drug classes steadily increased, with 10% more individuals prescribed at least one agent in 2023 than 2019. The largest increases were observed for behavioral health agents (e.g., 32.4% of the sample was prescribed psychotropic agents in 2023 compared with 25.7% in 2019). We provide considerations for future investigations. [ABSTRACT FROM AUTHOR]

Purpose To report historical patterns of pharmaceutical expenditures, to identify factors that may influence future spending, and to predict growth in drug spending in 2024 in the United States, with a focus on the nonfederal hospital and clinic sectors. Methods Historical patterns were assessed by examining data on drug purchases from manufacturers using the IQVIA National Sales Perspectives database. Factors that may influence drug spending in hospitals and clinics in 2024 were reviewed—including new drug approvals, patent expirations, and potential new policies or legislation. Focused analyses were conducted for biosimilars, cancer drugs, endocrine drugs, generics, and specialty drugs. For nonfederal hospitals, clinics, and overall (all sectors), estimates of growth of pharmaceutical expenditures in 2024 were based on a combination of quantitative analyses and expert opinion. Results In 2023, overall pharmaceutical expenditures in the US grew 13.6% compared to 2022, for a total of $722.5 billion. Utilization (a 6.5% increase), new drugs (a 4.2% increase) and price (a 2.9% increase) drove this increase. Semaglutide was the top drug in 2023, followed by adalimumab and apixaban. Drug expenditures were $37.1 billion (a 1.1% decrease) and $135.7 billion (a 15.0% increase) in nonfederal hospitals and clinics, respectively. In clinics, increased utilization drove growth, with a small impact from price and new products. In nonfederal hospitals, a drop in utilization led the decrease in expenditures, with price and new drugs modestly contributing to growth in spending. Several new drugs that will influence spending are expected to be approved in 2024. Specialty, endocrine, and cancer drugs will continue to drive expenditures. Conclusion For 2024, we expect overall prescription drug spending to rise by 10.0% to 12.0%, whereas in clinics and hospitals we anticipate an 11.0% to 13.0% increase and a 0% to 2.0% increase, respectively, compared to 2023. These national estimates of future pharmaceutical expenditure growth may not be representative of any health system because of the myriad of local factors that influence actual spending. [ABSTRACT FROM AUTHOR]

Background: Generic substitution policies have been widely implemented worldwide to enhance the accessibility of medications. Nevertheless, certain patients have voiced discontent with these policies. This study aimed to evaluate the patient preferences for generic substitution policies and explore the potential for optimization to enhance patient acceptance. Methods: A discrete choice experiment (DCE) was conducted to estimate the relative importance (RI) of five attributes, including generic consistency evaluation (GCE), reimbursement rate, medication use control, information disclosure, and post-marketing surveillance. Respondents were recruited among inpatients and outpatients in three cities and surveys were conducted face-to-face. Preference coefficients, RI of attributes, and the uptake rate of various policies were computed using a mixed logit model. The interaction effects were also included to examine preference heterogeneity. Results: A total of 302 patients completed the survey. All five attributes significantly impacted policy acceptance. GCE held the highest RI value at 56.64%, followed by reimbursement rate (RI = 12.62%), information disclosure (RI = 12.41%), post-marketing surveillance (RI = 9.54%), and medication use control (RI = 8.80%). Patient preferences varied depending on their gender and income. The patient uptake rate of China's current policy was only 68.56%. If all generics were to pass GCE without altering the other attributes, the uptake rate of policies would rise to 82.63%. Similarly, implementing information disclosure without changing other attributes would result in a 78.67% uptake rate, which is comparable to the effect of a 10% increase in reimbursement rate for generics (78.81%). Combining these policies could mitigate the adverse effects of mandatory substitution on patient. Conclusion: Chinese patient preferences for generic substitution policies were mainly influenced by GCE. China's current generic substitution policy has room for further optimization to enhance patient acceptance. [ABSTRACT FROM AUTHOR]

Introduction: The national volume-based drug procurement policy initiated in China since 2018 represents a significant reform in China's pharmaceutical distribution system. It has largely squeezed out the price bubble of low-end generic drugs, making competition in the pharmaceutical sales segment more intense and transparent. This policy intervenes in the distribution link of the pharmaceutical industry by intensifying market competition, thereby enhancing the innovation willingness and R&D capabilities of pharmaceutical companies. Methods: Taking the national volume-based drug procurement policy as the policy shock, we used the multi-period difference-in-difference method to study the impact of the policy on innovation input, innovation output quantity and innovation output quality of listed pharmaceutical companies and its impact mechanism. Results: We found that the volume-based policy can significantly promote the pharmaceutical companies' innovation input and the innovation output quality, but significantly reduced the innovation output quantity. For innovative and generic drug companies, this policy has limited impact on innovative drug companies, but force generic drug companies to pay more attention to cost control and market positioning, and the quality and cost-effectiveness of R&D output to ensure competitiveness in the market. For bid-winning and nonwinning companies, the policy has a greater innovation incentive for nonwinning companies than winning companies, by imposing greater survival pressure on non-winning companies, forcing them to increase R&D investment intensity and adopt the innovation strategy of preferring quality to quantity. Discussion: The results show that the national volume-based drug procurement policy should be expanded to lower drug prices and lighten the medical burden on patients, with enhanced quality and safety supervision. Additionally, it suggests cautious application of such policies to innovative and high-end generic drugs to encourage continued pharmaceutical innovation and industry advancement. [ABSTRACT FROM AUTHOR]

It is unknown to what extent medical researchers generalize study findings beyond their samples when their sample size, sample diversity, or knowledge of conditions that support external validity do not warrant it. It is also unknown to what extent medical researchers describe their results with precise quantifications or unquantified generalizations, i.e., generics, that can obscure variations between individuals. We therefore systematically reviewed all prospective studies (n = 533) published in the top four highest ranking medical journals, Lancet, New England Journal of Medicine (NEJM), Journal of the American Medical Association (JAMA), and the British Medical Journal (BMJ), from January 2022 to May 2023. We additionally reviewed all NEJM Journal Watch clinical research summaries (n = 143) published during the same time. Of all research articles reporting prospective studies, 52.5% included generalizations beyond specific national study populations, with the numbers of articles with generics varying significantly between journals (JAMA = 12%; Lancet = 77%) (p < 0.001, V = 0.48). There was no evidence that articles containing broader generalizations or generics were correlated with larger or more nationally diverse samples. Moreover, only 10.2% of articles with generalizations beyond specific national populations reported external validity strengthening factors that could potentially support such extrapolations. There was no evidence that original research articles and NEJM Journal Watch summaries intended for practitioners differed in their use of broad generalizations, including generics. Finally, from the journal with the highest citation impact, articles containing broader conclusions were correlated with more citations. Since there was no evidence that studies with generalizations beyond specific national study populations or with generics were associated with larger, more nationally diverse samples, or with reports of population similarity that may permit extensions of conclusions, our findings suggest that the generalizations in many articles were insufficiently supported. Caution against overly broad generalizations in medical research is warranted. [ABSTRACT FROM AUTHOR]

On March 16, 2018, in Rafferty v. Merck & Co., the Supreme Judicial Court of Massachusetts held that brand-name drug manufacturers owe generic drug users a duty to not act recklessly in creating and updating warning labels. Courts deciding this issue have disagreed about whether and to what extent a duty should be imposed on brand-name manufacturers concerning injuries caused by generic products they do not produce. The Supreme Judicial Court is among the minority of courts that has correctly imposed a duty on brand-name manufacturers in this context. Its imposition of a recklessness standard, however, is incorrect because it inappropriately weighs public policy concerns. [ABSTRACT FROM AUTHOR]

Patients are often switched between generic formulations of the same drug, but in some cases generic interchangeability is questioned. For generic drugs to be approved, bioequivalence with the innovator drug should be demonstrated, but evidence of bioequivalence is not required in the intended patient population or relative to other approved generics. Aim: We aim to identify pathophysiological pharmacokinetic subpopulations for whom there is a difference in comparative bioavailability compared to a healthy population. Methods: We used simulated exposures from a nonparametric model of multiple generics and the originator gabapentin. Exposure was simulated for virtual populations with pharmacokinetic characteristics beyond those of healthy subjects with regard to rate of absorption, volume of distribution and reduced renal function. Virtual parallel design bioequivalence studies were performed using a random sample of 24 simulated subjects, with standard acceptance criteria. Results: Results indicated increased pharmacokinetic variability for patient populations with a lower rate of absorption or a reduced renal function, but no change in the average comparable bioavailability ratio. This increased variability results in a reduced likelihood of demonstrating bioequivalence. Observations were similar for comparisons between all different formulations, as well as between subjects who received the identical formulation in a repeated fashion. No relevant effect was observed for simulations with increased volume of distribution. Conclusion: Our simulations indicate that the reduced likelihood of demonstrating bioequivalence for subjects with altered pharmacokinetics is not influenced by a formulation switch, nor does the average comparable bioavailability ratio change, therefore these results support generic interchangeability and current approval requirements for generics. [ABSTRACT FROM AUTHOR]

Despite >1 in 5 children taking prescription drugs in the United States, offlabel drug use is common. To increase the study of drugs in children, regulatory bodies have enacted legislation to incentivize and require pediatric drug studies. As a result of this legislation, novel trial approaches, and an increase in personnel with pediatric expertise, there have been numerous advancements in pediatric drug development. With this review, we aim to highlight developments in pediatric pharmacology over the past 6 years for the most common disease processes that may be treated pharmacologically by the pediatric primary care provider. Using information extracted from label changes between 2018 and 2023, the published literature, and Clinicaltrials.gov, we discuss advances across multiple therapeutic areas relevant to the pediatric primary care provider, including asthma, obesity and related disorders, mental health disorders, infections, and dermatologic conditions. We highlight instances in which new drugs have been developed on the basis of a deeper mechanistic understanding of illness and instances in which labels have been expanded in older drugs on the basis of newly available data. We then consider additional factors that affect pediatric drug use, including cost and nonpharmacologic therapies. Although there is work to be done, efforts focused on pediatric-specific drug development will increase the availability of evidence-based, labeled guidance for commonly prescribed drugs and improve outcomes through the safe and effective use of drugs in children. [ABSTRACT FROM AUTHOR]

Introduction Cariprazine is an atypical dopamine receptor partial agonist antipsychotic available in the form of capsules. Although capsules are one of the most desirable routes of administration, there are certain situations (e. g., in an acute psychiatric setting, or when swallowing difficulties, or liquid shortages are present) when they cannot be administered. Therefore, alternative solutions like orodispersible tablets are needed. This study aimed to investigate the bioequivalence of a newly developed orodispersible tablet to the commercially available hard gelatine capsule of cariprazine 1.5 mg. Methods This was a phase I, open-label, randomized, single-dose bioequivalence study. It had a 2-period, 2-sequence, cross-over design, where each subject received one test and one reference product in a randomized sequence, separated by a wash-out period of 55 days. Blood sampling was performed over 72 h after dosing. Cariprazine concentrations were analyzed by a validated HPLC-MS/MS method. Standard bioequivalence statistics was applied to PK parameters calculated by non-compartmental analysis. Safety measures were analyzed descriptively. Result Pharmacokinetic data of 43 healthy volunteers and safety data of 54 subjects was analyzed. Cariprazine AUC0–72h and Cmax geometric mean ratios were 117.76% and 100.88%, respectively. The 90% confidence intervals were within the pre-defined bioequivalence acceptance limits of 80.00% – 125.00%. Safety data was in line with the Summary of Product Characteristics of Cariprazine. Discussion The result of this clinical trial proved the bioequivalence of the new orodispersible tablet formulation when compared to hard gelatine capsules, enabling an alternative option for treatment of those suffering from schizophrenia. [ABSTRACT FROM AUTHOR]

The development of generic ophthalmic drug products with complex formulations is challenging due to the complexity of the ocular system and a lack of sensitive testing to evaluate the interplay of its physiology with ophthalmic drugs. New methods are needed to facilitate the development of ophthalmic generic drug products. Ocular physiologically based pharmacokinetic (O-PBPK) models can provide insight into drug partitioning in eye tissues that are usually not accessible and/or are challenging to sample in humans. This study aims to demonstrate the utility of an ocular PBPK model to predict human exposure following the administration of ophthalmic suspension. Besifloxacin (Bes) suspension is presented as a case study. The O-PBPK model for Bes ophthalmic suspension (Besivance® 0.6%) accounts for nasolacrimal drainage, suspended particle dissolution in the tears, ocular absorption, and distribution in the rabbit eye. A topical controlled release formulation was used to integrate the effect of Durasite® on Bes ocular retention. The model was subsequently used to predict Bes exposure after its topical administration in humans. Drug-specific parameters were used as validated for rabbits. The physiological parameters were adjusted to match human ocular physiology. Simulated human ocular pharmacokinetic profiles were compared with the observed ocular tissue concentration data to assess the OCAT models' ability to predict human ocular exposure. The O-PBPK model simulations adequately described the observed concentrations in the eye tissues following the topical administration of Bes suspension in rabbits. After adjustment of physiological parameters to represent the human eye, the extrapolation of clinical ocular exposure following a single ocular administration of Bes suspension was successful. [ABSTRACT FROM AUTHOR]

Bioequivalence studies are pivotal in generic drug development wherein therapeutic equivalence is provided with an innovator product. However, bioequivalence studies represent significant complexities due to the interplay of multiple factors related to drug, formulation, physiology, and pharmacokinetics. Approaches such as physiologically based biopharmaceutics modeling (PBBM) can enable virtual bioequivalence (VBE) assessment through appropriately developed and validated models. Such models are now being extensively used for bioequivalence risk assessment, internal decision-making, and the evaluation of drug and formulation factors related to bioequivalence. Depiction of the above-mentioned factors through the incorporation of variability and development of a virtual population for bioequivalence assessment is of paramount importance in utilizing such models. In this manuscript, we have portrayed our current understanding of VBE. A detailed explanation was provided with respect to study designs, in vivo variability, and the impact of physiological, drug, and formulation factors on the development of the population for VBE. Furthermore, strategies are suggested to incorporate variability in GastroPlus with an emphasis on intra-subject and inter-occasion variability. Two industrial case studies pertaining to immediate and modified release formulation were portrayed wherein VBE was utilized for decision-making and regulatory justification. Finally, regulatory understanding in the area of VBE, along with future perspectives, was detailed. [ABSTRACT FROM AUTHOR]

Background: Originator drug manufacturers use several strategies to delay generic competition in the USA, but it remains unclear whether this results in longer market exclusivity compared to other countries. Objectives: We sought to understand how drug market exclusivity lengths vary between the USA and two comparable countries. Methods: We focused on drugs approved within 2 years of each other in the USA, France, and Australia from 1995 to 2005, and we compared the lengths of exclusivity from marketing approval through first generic competition or June 2023 using Kaplan–Meier analyses. Results: Among 165 drugs in common between the USA and France, the median length of exclusivity was slightly longer in France (15.0 years, interquartile range [IQR]: 13.0–19.6) than the USA (14.5 years, IQR: 11.7–17.6). Among 100 drugs in common between the USA and Australia, the median length of exclusivity was longer in Australia (16.3 years, IQR: 13.9–22.4) than in the USA (14.4 years, IQR: 12.0–17.1). Conclusions: Market exclusivity lengths in the USA are not longer than in France and Australia. Potential reasons include the larger US market and incentives that offer transient high generic drug prices in the USA for manufacturers that successfully challenge originator market exclusivity. [ABSTRACT FROM AUTHOR]

Regulatory authorities must balance ensuring evidence of efficacy and safety of new drugs. Various regulatory pathways, such as the accelerated approval program in the United States (US), allow authorities to quickly approve drugs for severely ill patients by granting market authorization based on surrogate end points and pending confirmatory trials. In this cross‐sectional study, we considered 23 indications of cancer drugs that received accelerated approval by the US Food and Drug Administration (FDA) but were subsequently withdrawn as of April 2023. Our investigation extended to assessing the regulatory status of these accelerated approvals in the European Union (EU) and Japan, examining relevant regulatory documents and identifying factors contributing to the withdrawal in the United States. Comparing regions, we found that for 52% (12/23) and 30% (7/23) of withdrawn accelerated approvals in the United States, sponsors had also sought marketing authorization from the European Medicines Agency (EMA) and Japan's Pharmaceuticals and Medical Devices Agency (PMDA), respectively. As of the April 30, 2023 study cutoff date, 83% (10/12) of drug–indication pairs remained approved by the EMA, while the PMDA retained 100% (7/7). For these indications, the time from FDA withdrawal until the study cutoff date ranged from 0.23 years to 11.45 years for EMA approvals (median: 1.28 years) and 1.10 years to 11.45 years for PMDA approvals (median: 3.22 years). These findings highlight substantial regulatory discrepancies concerning cancer drugs with unconfirmed benefits. Addressing these discrepancies may involve requiring pharmaceutical companies to confirm clinical benefits using more robust end points and fostering international harmonization in regulators' assessment. [ABSTRACT FROM AUTHOR]