Environmental contamination by pharmaceutical residues accumulation in water bodies, risk of ecological disturbance and development of antimicrobial resistance have become a serious global threat. Pharmaceutical active ingredients and metabolites of these substances expelled into the surrounding environment by excretion, industrial wastewater and improper disposal practices result in measurable levels in surface waters and wastewater globally. In response, regulatory authorities incorporated Environmental Risk Assessment (ERA) requirements into the drug licensing system. For human medicinal products, a product-specific, tiered Environmental Risk Assessment (ERA) has been applied by the European Medicines Agency (EMA). NEPA-based environmental review involving applicable categorical exclusions and Environmental Assessments (EAs) has been utilized by the US Food and Drug Administration (FDA), whereas there is no dedicated medicinal-product ERA guideline within the NDCTR framework currently for India’s Central Drugs Standard Control Organisation (CDSCO), but have a broader environmental legislation addressing environmental protection. This article mainly compares the scope, methodology, requirements for data, how the data should be reported, and challenges of implementation of the ERA regulatory infrastructure among the EMA, FDA, and CDSCO. To show similarities and differences, comparison tables and flow diagrams are added. Regulatory gaps, mainly in India, and possibilities for harmonised ERA frameworks that can safeguard global health and biodiversity by encouraging regulatory consolidation are discovered by this study.
Since 2011, the Taiwan Food and Drug Administration (TFDA) has established various facilitated regulatory pathways (FRPs, including expedited and accelerated review frameworks) for new drug applications. In 2017 and 2019, TFDA implemented the Refuse to File (RTF) mechanism and conducted a comprehensive revision of FRPs, respectively. This study aims to evaluate the outcomes of these reforms from 2015 to 2024, focusing on New Active Substance (NAS) approvals, pathway utilization, and international comparison. NAS approvals between 2015 and 2024 were analyzed using TFDA’s internal regulatory database, with U.S. Food and Drug Administration (US FDA), European Medicines Agency (EMA), and Japan’s Pharmaceuticals and Medical Devices Agency (Japan’s PMDA) data obtained from public sources. Analyses and visualizations were conducted with R. Following the 2017 and 2019 reforms, the on-time rate for the 360-day standard pathway surged from 19.0
In Peru, the regulatory framework governing clinical research has evolved substantially, particularly during the COVID-19 pandemic; however, recent patterns of authorized clinical trials (CTs) have not been systematically described. To characterize authorized CTs in Peru and to describe their evolution across the pre-pandemic (2017–2019), pandemic (2020–2022), and post-pandemic (2023–2025) periods. Retrospective descriptive study using secondary data from the Peruvian Clinical Trial Registry (REPEC). All CTs authorized between January 2017 and December 2025 were included. Trial, population, geographic, and regulatory characteristics were assessed. Categorical variables were compared using chi-square or Fisher’s exact tests, and continuous variables using the Kruskal–Wallis test. A total of 421 authorized CTs were analyzed. Most were foreign-sponsored (90.0
Power-based sample size calculation is the standard approach in confirmatory clinical trials, where adequate statistical power is essential for study success. In other decision-making contexts, however, a precision-based approach to sample size determination is sometimes adopted. One such area is consumer studies that evaluate consumers’ ability to appropriately select nonprescription medications. Compared with power-based designs, precision-based approaches typically require fewer study participants and can therefore reduce study costs. However, the extent of loss in statistical power has not been well quantified. In this paper, we evaluate the statistical power of precision-based sample size determination and illustrate its practical implementation. Our analysis demonstrates that when the target precision is set to the difference between the expected proportion and the null threshold, the resulting design achieves only approximately 50
Precision medicine has revolutionized oncology by leveraging biomarkers for individualized therapy selection, early diagnosis, and real-time disease monitoring. However, the application of biomarkers in non-oncology therapeutic areas remains comparatively underdeveloped despite significant potential. This narrative review explores the evolving role of biomarkers across cardiovascular, renal, neurological, metabolic, and respiratory diseases, focusing on their clinical and regulatory contexts of use—diagnostic, prognostic, predictive, surrogate, safety, and pharmacodynamic/response. Key examples include high-sensitivity troponins and natriuretic peptides in cardiology, NGAL and KIM-1 in nephrology, NfL in neurology, and HbA1c in diabetes, each illustrating how molecular markers improve disease characterization, guided therapy, and accelerate clinical development. By integrating multi-omics technologies, artificial intelligence, and standardized validation frameworks, the field is poised to extend the benefits of precision medicine well beyond oncology. Ultimately, establishing robust biomarker infrastructures across non-cancer domains will enhance patient stratification, optimize drug development efficiency, and enable personalized therapeutic strategies across a broad spectrum of chronic diseases.
Recently, polyethylene glycol modification has become key to improving biopharmaceutical pharmacokinetics and clinical applicability. This study aims to build a comprehensive analytical framework that integrates current status analysis, technology flow, and value assessment, in order to provide a step-by-step and thorough characterization of the patent landscape for PEG-modified drugs. Using the Derwent patent database, this study compiled 99,540 PEG-related patents worldwide from 2014 to 2023. Descriptive statistics, social network analysis, machine learning, and deep learning methods were applied to analyze these patents. The number of related patents increased dramatically over the past decade. China filed the most patents (24303) but exhibited a narrower technological breadth, while the United States led in numbers of inventors (86208) and assignees (37045). Patents from developed regions are more likely to be cited, and patent transfer activities mainly occur between commercial institutions. PEG-modified proteins and peptides represent the most commercially active category, highlighting their current market relevance. For patent transfer prediction, the XGBoost model achieved an average accuracy of 88.15
Hyperlipidemia is a major modifiable contributor to atherosclerotic cardiovascular disease (ASCVD). Despite statins as first-line therapy, residual cardiovascular risk, treatment intolerance, and genetic dyslipidemias highlight the need for innovative strategies. This narrative review critically evaluates emerging biotechnology- and artificial intelligence (AI)-enhanced approaches for hyperlipidemia, emphasizing translational maturity, clinical applicability, and regulatory implications. A structured literature search of PubMed/MEDLINE, Scopus, and Web of Science Core Collection was conducted to identify relevant evidence published primarily between January 2015 and February 2025. The review methodology, including the approximate literature search yield, is described in the Methods section. Evidence was synthesized across three developmental tiers: preclinical and early clinical gene-editing strategies; clinically established or late-stage therapies, including PCSK9 monoclonal antibodies and inclisiran; and early translational or conceptual platforms involving nanotechnology, microbiome modulation, and AI-assisted treatment optimization. PCSK9 monoclonal antibodies provide substantial LDL-C reduction and established cardiovascular outcome benefits, whereas inclisiran offers durable LDL-C lowering with infrequent dosing, although definitive cardiovascular outcomes evidence remains pending. CRISPR-based approaches may enable durable lipid regulation but remain constrained by delivery efficiency, off-target effects, immunogenicity, and long-term safety concerns. Nanoparticle-based delivery, microbiome-targeted interventions, and AI-driven prediction and treatment optimization are promising, but clinical translation is limited by biological variability, standardization challenges, insufficient external validation, algorithmic bias, data-governance concerns, and workflow integration barriers. Biotechnology and AI are reshaping precision lipid management. Successful translation will require long-term safety and outcomes validation, reproducible delivery platforms, cost-effectiveness, equitable implementation, and adaptive regulatory frameworks.
To establish meaningful within-patient change (MWPC) thresholds for the Psychomotor Vigilance Test (PVT) and evaluate whether treatment with the orexin-2 receptor agonist oveporexton (TAK-861) achieved clinically meaningful improvements in attention in people with narcolepsy type 1 (NT1). Attention was assessed as number of lapses (reaction times > 500 ms) on the PVT using data from 2 randomized placebo-controlled phase III trials, The First Light (N = 166) and The Radiant Light (N = 105). Anchor-based methods, supported by distribution-based methods, were used to derive MWPC estimates. Mean changes in square root−transformed PVT lapses (to account for data skewness) were calculated across anchor change categories, with weighted MWPC estimates derived across anchors. Estimates were confirmed with post-hoc receiver operating characteristic (ROC) curve analysis. The proportions of participants meeting MWPC criteria were compared between oveporexton and placebo arms, with odds ratios and 95
For several decades, the United States (U.S.) has been the leader in biopharmaceutical advancements. Recently, the U.S. has increased government interventions to limit prices for patent-protected medicines. While it is unclear whether ongoing efforts to implement international reference pricing in the U.S. could have similar effects, descriptive measures of global biopharmaceutical market dynamics can help benchmark future assessments. In this analysis, we analyzed trends in the geographic distribution of select measures of biopharmaceutical leadership from 2004 through 2024. Using the PharmaProjects database from Citeline, we found that 43.1
Some US payers delay coverage for non-oncology treatments approved via the Food and Drug Administration (FDA)’s accelerated approval (AA) pathway. To estimate the economic burden and characteristics of diseases with therapies approved via the AA pathway compared to diseases with no AA therapies. The study identified the initial FDA-approved AA indications for all non-oncology therapies from January 2015 to February 2025. For comparison, 100 non-oncology diseases with the most recent FDA-approved non-AA therapies were identified. Annual economic burden and disease characteristics were extracted from peer-reviewed literature, with costs inflated to 2025 USD. Economic burden studies that used a societal perspective were prioritized. Comparative analyses were conducted using the Mann–Whitney U Test. Thirty-two non-oncology AA treatments were identified representing 16 unique diseases. Average annual incremental societal costs for AA diseases were 1.4 times higher than for non-AA diseases (91,857 vs.65,468, p = 0.012). Additionally, the annual average productivity loss and caregiver burden were 1.8 times (17,635 vs.9,620, p = 0.092) and 2.4 times (20,268 vs.8,294, p = 0.055) greater in the AA diseases, respectively. Diseases with newly-approved AA treatments were characterized by shorter life expectancy (59.3 vs 65.1 years), lower average quality of life (0.64 vs 0.69), and more likely to be rare diseases (68.8
This study aimed to evaluate the effects of psychotropic drug scheduling, including limiting the days’ supply per prescription, on the prescriptions of etizolam and zopiclone, benzodiazepine receptor agonists (BZRAs), in Japan. This study was based on the randomly sampled data from the national administrative health insurance claims data in Japan from 2012 to 2020. We analyzed age-specific trends in prescriptions of the two BZRAs, which were designated as psychotropic drugs in 2016. The impacts of psychotropic drug scheduling on the prescription trends were evaluated using interrupted time series analysis. After the scheduling, etizolam prescriptions showed an immediate decrease and a continuing decrease at a greater rate than before the intervention in patients aged 80 years or older (Level [per 10,000 people], −22.23, 95
Clinical settings generate real-world data (RWD), which offers valuable insights into pharmaceutical effectiveness and safety. Agencies, such as the U.S. Food and Drug Administration (FDA), the European Medicines Agency (EMA), and Pharmaceuticals and Medical Devices Agency (PMDA) of Japan, are increasingly using Real-World Evidence (RWE) in their decision-making processes. Registries play a critical role in RWE studies by systematically collecting patient data. Implementing stringent quality control and quality assurance measures is essential to achieve RWD reliability. This study identified the essential quality elements for registry-based RWD and developed a proposed data quality management checklist. A scoping review of peer-reviewed literature and regulatory guidelines published between 2001 and 2026 was conducted using PubMed, Embase, and the websites of major regulatory agencies. Eligible studies included those addressing RWD, RWE, and data quality checklist relevant to registry-based research. In total, 30 sources, comprising 24 publications and 6 institutional guidelines, were included. The analysis identified two core dimensions of data quality: relevance (availability, sufficiency, and representativeness) and reliability (accuracy, completeness, provenance, and timeliness). We developed a quality assessment checklist that addresses the following four key domains: study design, data collection and management, regulatory compliance, and continuous improvement. The proposed checklist offers a structured framework to enhance the reliability of RWD and enable systematic quality assessment. Future studies should assess its applicability across various research settings. This study supports robust data quality management, benefiting researchers, regulatory agencies, pharmaceutical companies, and healthcare institutions.
Integral drug-device combinations (iDDCs) are governed in the European Union (EU) under the medicinal products framework, but the medical device part must meet relevant requirements of the medical device framework. This implies increased complexity as actors with different responsibilities, expertise and priorities are involved. Regulation (EU) 2017/745 on medical devices (MDR) [1] came into effect on 26 May 2021. At the time of the repealed Council Directive 93/42/EEC on medical devices (MDD) [2], the European Medicines Agency (EMA) and EU National Competent Authorities (NCAs) were overseeing the evaluation of the quality, safety, efficacy, benefit/risk of the medicinal product and the relevant Essential Requirements according to the MDD of the integral medical device used in combination. Article 117 of the MDR introduced a fundamental change: notified bodies became responsible for assessing compliance of the integral medical device with the relevant General Safety and Performance Requirements (GSPRs), as set out in MDR Annex I. These GSPRs represent a more stringent set of requirements in comparison with the Essential Requirements in the MDD. One of the objectives of Article 117 and the MDR was to strengthen regulatory oversight of the device component of the iDDC and increase confidence in the regulatory system. Given the interface of the medicinal product and medical device legislations, the regulatory process for initial authorisation and lifecycle management of iDDCs is challenging to operate for pharmaceutical industry, EMA, EU NCAs and notified bodies. In particular, the implementation of Article 117 raised challenges to all stakeholders involved. In order to support implementation for pharmaceutical industry and EU medicines NCAs, EMA published dedicated guidance and engaged in various conferences and stakeholder meetings. EMA also facilitated discussion of issues with different actors and enhance mutual understanding and sharing of experience. Here, we present EMA's perspective on Article 117 implementation challenges and opportunities to tackle them.
Using survey data gathered for an Externally-Led Patient-Focused Drug Development (EL-PFDD) meeting led by the schizophrenia community to inform the US Food and Drug Administration, this publication examines schizophrenia’s impacts on daily life, reasons for discontinuation of medication, and desired outcomes of future medications. An online, cross-sectional survey about schizophrenia’s impacts on daily life, treatment experiences, and desired outcomes of future medications was developed for adults with schizophrenia and caregivers of adults with schizophrenia who could not complete the survey. Patient advocacy organizations participating in the EL-PFDD meeting recruited respondents via email and social media between August 9, 2022 and September 26, 2022. 282 survey responses from 96 people with schizophrenia and 186 caregiver proxies are reflected in this publication. Both respondent groups reported significant impacts of schizophrenia on aspects of daily living spanning work and education, relationships, responsibilities at home, and finances. For people with schizophrenia, the most frequently reported reason for discontinuing medications was weight gain (66
The Delphi technique is a structured method for achieving expert consensus and is widely used in health research, including studies involving pharmaceutical sponsors. Although guidance exists for the conduct and reporting of Delphi studies, methodological and reporting practices remain variable. This systematic review aimed to characterise the design, reporting, and transparency of Delphi studies with pharmaceutical sponsor involvement. A systematic literature review identified Delphi studies published between 2020 and 2024 that reported pharmaceutical sponsor involvement. Studies were screened and data extracted using a standardised framework informed by published Delphi guidance. Extracted variables included study aims, panel composition and selection criteria, Delphi process design, consensus definitions, reporting practices, and descriptions of sponsor involvement. Methodological quality was assessed using a four-item framework focused on core Delphi design elements. Eighty-two studies met the inclusion criteria. Substantial heterogeneity was observed in study design and reporting. While most studies prespecified a consensus definition, the rationale for consensus thresholds and approaches to handling disagreement were inconsistently reported. Details regarding panel recruitment, feedback between rounds, and statement modification were variably described. Reporting of sponsor involvement also differed across studies. Overall methodological quality varied, with many studies meeting only a subset of core quality criteria. Delphi studies involving pharmaceutical sponsors show substantial variation in methodological approaches, alongside incomplete reporting of key design elements and sponsor involvement. More consistent reporting of key design elements and sponsor involvement may improve transparency and interpretability. The proposed TRIAD framework offers a structured approach to support transparent reporting in future Delphi studies.
Serious breaches are significant deviations that may compromise participant safety or data integrity in clinical trials. Public reports in the EU CTIS offer a valuable, though limited, opportunity to examine reporting practices and identify potential operational gaps. This study used a mixed-methods approach to analyze publicly available CTIS serious breach notifications. All publicly available CTIS serious breach notifications were reviewed. Quantitative variables included (i) the interval from breach occurrence to sponsor awareness and (ii) the interval from sponsor awareness to public posting in CTIS. Qualitative assessment employed descriptive content analysis to categorize breach themes. Most cases were assigned to the Protocol category (n = 50, 72.5
Good Laboratory Practice (GLP) emerged in the 1970s in response to serious deficiencies in the validity and reproducibility of preclinical safety data submitted in the USA. Non-adherence to scientific standards in the use of laboratory methods and the data generated, and even fraudulent practices, led to the establishment of binding regulatory standards, which were later adopted by the OECD as the "Principles of GLP", alongside the Council Decision on the Mutual Acceptance of Data (MAD). This framework, expanded to include compliance monitoring programmes and non-member country participation and has since formed the foundation for international harmonization of non-clinical safety testing. Germany, as an early adopter of the OECD GLP system, provides a prominent example of long-term implementation. Since the national compliance monitoring programme became legally binding in 1990, thousands of inspections were carried out in the meantime. German test facilities cover all OECD-defined areas of expertise and the German compliance monitoring authorities maintain rigorous inspection cycles in line with OECD recommendations, with a notable share operating for decades within the programme. This long-standing infrastructure in Germany contributes to the reliable and robust application of the OECD's GLP principles. This article presents a comprehensive overview of the historical development, international transposition and national application of GLP, using Germany as a case study after 35 years of implementation. By compiling regulatory milestones, structural data, and long-term monitoring outcomes, the publication aims to provide a transparent evidence base for assessing the effectiveness of GLP frameworks. The systematic presentation of these data serves both to document Germany's contribution to the international GLP landscape and to support ongoing discussions on harmonization, resource allocation, and future challenges in non-clinical safety assessment.
This review highlights the problem of protein molecule aggregation, which represents a significant challenge in the field of biopharmaceuticals. Protein aggregation is critical because it can affect the efficacy and safety of biopharmaceuticals, including those used to treat autoimmune diseases and various cancers. From a regulatory perspective, protein aggregation is recognized as a critical quality attribute (CQA) by health authorities such as the FDA and EMA, due to its potential impact on immunogenicity, product consistency, and patient safety. This article reviews various aggregation mechanisms, pathways, and strategies to minimize aggregation at various stages of drug development and manufacturing. Attention is paid to the latest analytical control techniques, addressing their applicability and limitations, as well as the possibility of integrating them into the QC flow, in alignment with current regulatory expectations for robust, science- and risk-based control strategies. The QbD principles emphasize their role in improving the understanding of manufacturing processes and enhancing the quality of finished pharmaceutical products, consistent with ICH Q8–Q11 guidelines and the regulatory push toward lifecycle-based pharmaceutical quality systems. The article offers valuable recommendations for the scientific community and manufacturers to effectively address protein aggregation and improve the safety and efficacy of biopharmaceuticals, while supporting regulatory compliance and facilitating more predictable interactions with health authorities.
