Therapeutic innovation & regulatory science最新文献

{"title":"Advancing Oncology Drug Development in the US: The Interplay between Innovations and Regulatory Science.","authors":"Yannan Nancy Dou, Jian Wang","doi":"10.1007/s43441-025-00800-3","DOIUrl":"https://doi.org/10.1007/s43441-025-00800-3","url":null,"abstract":"<p><p>The landscape of drug development has evolved with the adoption of new therapeutic modalities, cutting-edge technology platforms, emerging scientific insights, and modern patient-centric clinical trial designs. In this review, we investigate the interplay between innovation and regulatory science in cancer drug development in the United States. As new innovations emerge, regulatory science adapts to integrate new discoveries and technologies, ensuring alignment with established regulations and safety standards. This fuels additional innovations through data and evidence generation, potentially expediting the development of revolutionary treatments and advancing patient access to novel, promising therapies. Early and frequent engagement with regulators is vital for drug developers aiming to successfully apply innovative approaches.</p>","PeriodicalId":23084,"journal":{"name":"Therapeutic innovation & regulatory science","volume":" ","pages":""},"PeriodicalIF":2.0,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144128810","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genome Editing in Gynecological Oncology: The Emerging Role of CRISPR/Cas9 in Precision Cancer Therapy.","authors":"Naina Kumar","doi":"10.1007/s43441-025-00807-w","DOIUrl":"https://doi.org/10.1007/s43441-025-00807-w","url":null,"abstract":"<p><strong>Introduction: </strong>Gynecological cancers, including cervical, ovarian, and endometrial cancers, represent a significant global health challenge due to their high prevalence and profound impact on mortality and quality of life. This narrative review explores the transformative capability of genome editing, specifically clustered regularly interspaced short palindromic repeats (CRISPR/Cas9) technology, in advancing the management of these cancers. Genome editing offers great opportunities to develop targeted therapies by enabling precise modifications of genes involved in cancer initiation, progression, and chemoresistance.</p><p><strong>Methodology: </strong>A comprehensive literature search was conducted from October 2004 to October 2024. Only peer-reviewed relevant English articles with substantial insights into the impact of genome editing on cancer therapies were considered using keywords such as \"CRISPR/Cas9,\" \"genome editing,\" \"gynecological cancers,\" and specific cancer types like \"cervical cancer,\" \"ovarian cancer,\" and \"endometrial cancer.\"</p><p><strong>Conclusion: </strong>Genome editing, particularly CRISPR/Cas9, holds substantial capacity for revolutionizing the treatment landscape of gynecological cancers by enabling highly specific, gene-targeted therapies that can overcome conventional treatment limitations such as chemoresistance and tumor recurrence. Emerging preclinical studies demonstrate the feasibility of correcting oncogenic mutations and enhancing the sensitivity of tumors to existing therapies. However, before clinical translation can be realized, critical challenges-including off-target effects, delivery system optimization, and immune responses-must be systematically addressed through rigorous research and clinical trials. Advancing these solutions will be essential for safely integrating CRISPR-based interventions into personalized medicine approaches for gynecological malignancies.</p>","PeriodicalId":23084,"journal":{"name":"Therapeutic innovation & regulatory science","volume":" ","pages":""},"PeriodicalIF":2.0,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144111996","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Recent Updates to the Declaration of Helsinki: A View from the U.S. Food and Drug Administration.","authors":"Robert M Califf, Ann Meeker-O'Connell, Shari Targum, Hilary Marston","doi":"10.1007/s43441-024-00734-2","DOIUrl":"https://doi.org/10.1007/s43441-024-00734-2","url":null,"abstract":"<p><p>This commentary provides the perspective of the U.S. Food and Drug Administration (FDA) on the World Medical Association's (WMA) recent updates to the Declaration of Helsinki, a foundational document in biomedical research ethics. We highlight the value of an enduring principles-based approach in permitting such ethical codes to retain relevance over time; explain the different role that such codes and FDA regulations play in assuring the rights, safety, and welfare of research participants; and outline key changes in the Declaration, including a welcome shift in how vulnerability in research participants should be evaluated and managed. In the context of the rapidly evolving use of technology, we encourage ongoing engagement of global regulators, ethicists, and the broader research community as WMA revisits ethical norms related to health databanks, biobanks, and the use of novel computational methods in biomedical research. Clinical research is global in nature, and ensuring ethical treatment of research participants and their communities requires our continued collective commitment.</p>","PeriodicalId":23084,"journal":{"name":"Therapeutic innovation & regulatory science","volume":" ","pages":""},"PeriodicalIF":2.0,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144110889","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficiency of Lifecycle Management for Medicinal Products in the EU: Industry Experience with Variations to Implement a New European Pharmacopoeia Active Substance Monograph for a Generic Eye Drops Solution - A Case Study.","authors":"Fabian P Schwarb, Betty Lämmel, Beatrice A Harder Engelhard","doi":"10.1007/s43441-025-00802-1","DOIUrl":"https://doi.org/10.1007/s43441-025-00802-1","url":null,"abstract":"<p><strong>Background: </strong>While numerous efforts were taken by the regulators globally to have more streamlined and predictable post-approval CMC variation procedures, there are still areas where cumbersome and parallel assessments of variations may delay implementation of important CMC changes and bind resources in industry and regulatory authorities.</p><p><strong>Methods: </strong>In this case study a switch from an ASMF (Active Substance Master File) to the CEP (Certification of Suitability to the monographs of the European Pharmacopoeia) for an already approved manufacturer used for a generic ophthalmic formulation with 38 licenses (Marketing Authorisations, MAs) in the EEA was selected to investigate time needed for generation, submission and approval of variations as well as consistency of variation classification by experienced regulatory professionals and Competent Authorities (CAs), respectively.</p><p><strong>Results: </strong>Overall, four variations were needed for the change from an ASMF to the CEP to cover the concomitant changes that were required to fully align with the European Pharmacopoeia (Ph. Eur.) requirements for the active substance and consequentially for drug product. In one case the CA requested a 5th variation to cover the switch from in-house to Ph. Eur.</p><p><strong>Requirements: </strong>While average CAs approval time was 4.6 (± 2.1) months (range 2-8 months), overall it took 15.2 (± 2.8) months (range 11-20 months) from data collection and variation generation by the CDMO (Contract Development and Manufacturing Organization) until approval by the respective CA. Good alignment was achieved for most of the aspects, however, when implementation of Ph. Eur. requirements included removal or widening of acceptance criteria, there were quite diverse opinions on the classification by regulatory professionals and CAs, resulting in the same change to be approved as Type IA, Type IB, and Type II variations, respectively, in the different EEA countries.</p><p><strong>Conclusions: </strong>The long lead times and inconsistent variation classifications hamper switching to a new CEP or adding a new active substance supplier. More efficiency in variation regulations would be beneficial to allow for faster implementation of changes to assure the supply chain.</p>","PeriodicalId":23084,"journal":{"name":"Therapeutic innovation & regulatory science","volume":" ","pages":""},"PeriodicalIF":2.0,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144102685","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Companion Diagnostic FDA Review Flexibilities: An Assessment of CDx for NSCLC to Support Aligned Approaches for Validation.","authors":"Hillary S Andrews, Grace Collins, Bernat Navarro-Serer, Mark D Stewart, Jeff D Allen","doi":"10.1007/s43441-025-00799-7","DOIUrl":"https://doi.org/10.1007/s43441-025-00799-7","url":null,"abstract":"<p><p>The U.S. Food and Drug Administration (FDA) recommends concurrent development of targeted therapies with an associated companion diagnostic (CDx) as the optimal approach to provide patient access to novel, safe, and effective treatments. However, CDx validation often relies on clinical samples from pivotal clinical trials for the drug, which can be challenging, particularly when there is limited sample availability. A review of Summary of Safety and Effectiveness Data (SSED) documents for CDx approved for non-small cell lung cancer (NSCLC) revealed that CDx for rare biomarkers often use alternative samples for validation. While the practice of using alternative samples for validation occurs, it is not always clear when these flexibilities are considered or how alternative samples should be used for validation. To address this, we propose the FDA establish guidance for the use of alternative sample sources for CDx validation, especially for rare biomarkers, to ensure timely and effective patient access to targeted therapies.</p>","PeriodicalId":23084,"journal":{"name":"Therapeutic innovation & regulatory science","volume":" ","pages":""},"PeriodicalIF":2.0,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144080375","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Using Large Language Models for Advanced and Flexible Labelling of Protocol Deviations in Clinical Development.","authors":"Min Zou, Leszek Popko, Michelle Gaudio","doi":"10.1007/s43441-025-00785-z","DOIUrl":"https://doi.org/10.1007/s43441-025-00785-z","url":null,"abstract":"<p><strong>Background: </strong>As described in ICH E3 Q&A R1 (International Council for Harmonisation. E3: Structure and content of clinical study reports-questions and answers (R1). 6 July 2012. Available from: https://database.ich.org/sites/default/files/E3_Q%26As_R1_Q%26As.pdf ): \"A protocol deviation (PD) is any change, divergence, or departure from the study design or procedures defined in the protocol\". A problematic area in human subject protection is the wide divergence among institutions, sponsors, investigators and IRBs regarding the definition of and the procedures for reviewing PDs. Despite industry initiatives like TransCelerate's holistic approach [Galuchie et al. in Ther Innov Regul Sci 55:733-742, 2021], systematic trending and identification of impactful PDs remains limited. Traditional Natural Language Processing (NLP) methods are often cumbersome to implement, requiring extensive feature engineering and model tuning. However, the rise of Large Language Models (LLMs) has revolutionised text classification, enabling more accurate, nuanced, and context-aware solutions [Nguyen P. Test classification in the age of LLMs. 2024. Available from: https://blog.redsift.com/author/phong/ ]. An automated classification solution that enables efficient, flexible, and targeted PD classification is currently lacking.</p><p><strong>Methods: </strong>We developed a novel approach using a large language model (LLM), Meta Llama2 [Meta. Llama 2: Open source, free for research and commercial use. 2023. Available from: https://www.llama.com/llama2/ ] with a tailored prompt to classify free-text PDs from Roches' PD management system. The model outputs were analysed to identify trends and assess risks across clinical programs, supporting human decision-making. This method offers a generalisable framework for developing prompts and integrating data to address similar challenges in clinical development.</p><p><strong>Result: </strong>This approach flagged over 80% of PDs potentially affecting disease progression assessment, enabling expert review. Compared to months of manual analysis, this automated method produced actionable insights in minutes. The solution also highlighted gaps in first-line controls, supporting process improvement and better accuracy in disease progression handling during trials.</p>","PeriodicalId":23084,"journal":{"name":"Therapeutic innovation & regulatory science","volume":" ","pages":""},"PeriodicalIF":2.0,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144014765","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Awareness and Attitudes Regarding Adverse Drug Events and Reporting in South Africa.","authors":"Nokukhanya Ncube, Martha S Lubbe, Hanlie Steyn, Nkengafac V Motaze","doi":"10.1007/s43441-025-00795-x","DOIUrl":"https://doi.org/10.1007/s43441-025-00795-x","url":null,"abstract":"<p><strong>Background: </strong>Reporting of adverse drug events (ADEs), by consumers enhances medication-related risk surveillance, public awareness, and understanding of medicine safety. The aim of this study was to explore adults' awareness of ADEs, attitudes towards reporting and perceptions of their role in reporting ADEs in South Africa.</p><p><strong>Method: </strong>We conducted a cross-sectional, analytical study in which adults residing in South Africa completed an online questionnaire. The data collected was analysed using both descriptive and inferential statistics.</p><p><strong>Results: </strong>We received responses from 350 participants. Most participants (86.2%, n = 302; N = 350) reported having heard about ADEs and the majority of participants (94.4%, n = 301; N = 319) indicated that reporting of ADEs was important. The Med Safety App was not widely known (17.3%, n = 58; N = 336) while the South African Health Products Regulatory Authority (SAHPRA) was relatively well known (77.4%, n = 260; N = 336). Healthcare providers only educated 55.7% (n = 180; N = 323) of the participants about ADEs and only 50.5% (n = 163; N = 323) of the participants asked their healthcare providers about ADEs. Awareness regarding ADEs was significantly higher (p < 0.001) among healthcare professionals (HCPs) compared to non-healthcare professionals (non-HCP).</p><p><strong>Conclusion: </strong>Most participants were aware of ADEs and agreed it was important to report ADEs although reporting tools, such as the Med Safety App, were not well known. We recommend awareness campaigns on reporting processes because this could improve consumer reporting of ADEs in South Africa.</p>","PeriodicalId":23084,"journal":{"name":"Therapeutic innovation & regulatory science","volume":" ","pages":""},"PeriodicalIF":2.0,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144038820","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Considerations and Approaches to Establishing Estimates of Meaningful Change for Digital Endpoints as Drug Development Tools.","authors":"Marie Mc Carthy, Joseph C Cappelleri, Bill Byrom, Helen Doll, Junrui Di, Charmaine Demanuele, Joan Buenconsejo, Cheryl D Coon","doi":"10.1007/s43441-025-00794-y","DOIUrl":"https://doi.org/10.1007/s43441-025-00794-y","url":null,"abstract":"<p><strong>Objectives: </strong>This paper seeks to identify some of the complexities associated with determining meaningful change for endpoints derived from digital health technologies (DHTs) and propose possible methodologies for this process. Ultimately, this is a call to action to consider appropriate methods and practices required to enable digital endpoints (DEs) to achieve their full potential as Drug Development Tools.</p><p><strong>Methods: </strong>Using the Food and Drug Administration (FDA) Patient-Focused Drug Development (PFDD) guidance documents as a framework, we explore the nuances and challenges that exist when determining meaningful change for DEs compared with traditional clinical outcome assessments (COAs).</p><p><strong>Results: </strong>There are unique characteristics associated with DEs that provide distinct challenges when determining meaningful change. This complexity spans the totality of meaningful change considerations, from ensuring that the DE itself is meaningful from the patient perspective to selecting appropriate anchors that enable determination of the magnitude of change that is meaningful for patients.</p><p><strong>Conclusions: </strong>With increased adoption of DHTs in clinical trials, their specific use is evolving, as evidenced by their being referred to as DHT-passive monitoring COAs in the FDA drug development tool (DDT) qualification program. However, the determination of meaningful change for these DEs can be more nuanced and challenging than for traditional COAs. Merely adapting existing approaches for traditional COAs does not readily support DEs derived from continuous datasets collected over long periods. New methods and approaches are required, and this can only be realised by working together, to ensure that the value and limitations of various methodologies as they relate to DEs can be refined.</p>","PeriodicalId":23084,"journal":{"name":"Therapeutic innovation & regulatory science","volume":" ","pages":""},"PeriodicalIF":2.0,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143996221","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Benchmarking Medical Information Services Beyond the Unsolicited Requests: A phactMI Benchmarking Survey.","authors":"Michael J DeLuca, Rena Rai, Kirtida Pandya, Lillian Chavez, Prachee Satpute, Michael Rocco, Parul Shah, Jen Multari, Michael Cuozzo, Evelyn R Hermes-DeSantis","doi":"10.1007/s43441-025-00787-x","DOIUrl":"https://doi.org/10.1007/s43441-025-00787-x","url":null,"abstract":"<p><strong>Objective: </strong>Medical Information has a strategic role that extends beyond inquiry management. The Pharma Collaboration for Transparent Medical Information (phactMI™) benchmarking survey of 35 US pharmaceutical companies was conducted to describe the current landscape and future opportunities of other services Medical Information could provide.</p><p><strong>Methods: </strong>In July 2023, an electronic survey containing 57 closed and open-ended questions was distributed to phactMI member companies. The survey questions addressed demographics, medical review, development of materials, training, patient services, insights, and awareness.</p><p><strong>Results: </strong>Medical Information is a significant contributor to the medical review of promotional healthcare provider materials (51%), patient materials (52%), and non-promotional medical materials (45%). Medical Information ensures the accuracy of medical information, fact checks and validates claim accuracy. Fifty percent of the respondents are responsible for reviewing and/or contributing to Medical Affairs material for Field Medical. Additionally, Medical Information trains both Field Medical and Sales teams on the Medical Information function, and to a lesser extent, disease state information. The majority (75%) of Medical Information Departments offer patient information. The vast majority (85%) produce and identify insights. Medical Directors, Field Medical, and Scientific Communications/ Publications often receive shared insights. Fewer individuals integrate insights with Field Medical and Medical Directors. Since 2018, Medical Information activities have seen a rise in advisory board presentations, insights reporting, publications, competitive intelligence, disease state education, surveillance, pathway submission, and labelling activities. Building awareness is still an important aspect of Medical Information and most focus on the development of their Medical Information website.</p><p><strong>Conclusion: </strong>The essential roles and activities of Medical Information Departments support products at every stage. Medical Information participates with multiple functions in evaluating medical materials and there is a growing trend of including Medical Information in the development and review of Medical Affairs materials. Medical Information has expanded its participation in pathway submissions, publications, and labeling activities. This benchmark for Medical Information can provide a potential best practice template for activities. For the future, the three areas to prioritize are: increasing the strategic value and KPIs of Medical Information, integrating and overseeing AI technology in the insights process, and improving internal visibility.</p>","PeriodicalId":23084,"journal":{"name":"Therapeutic innovation & regulatory science","volume":" ","pages":""},"PeriodicalIF":2.0,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143987503","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Applying Aggregate Statistical Analyses to Safety Monitoring of Ongoing Clinical Studies, Issues, and Opportunities in a Test Case.","authors":"Ed Whalen, Steven Gilbert, James Buchanan","doi":"10.1007/s43441-025-00776-0","DOIUrl":"https://doi.org/10.1007/s43441-025-00776-0","url":null,"abstract":"","PeriodicalId":23084,"journal":{"name":"Therapeutic innovation & regulatory science","volume":" ","pages":""},"PeriodicalIF":2.0,"publicationDate":"2025-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143987502","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}