Therapeutic innovation & regulatory science最新文献

{"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":"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":"937-948"},"PeriodicalIF":1.9,"publicationDate":"2025-09-01","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":"The Challenges in the Regulatory Approval of Additive-Manufactured Medical Devices: A Quantitative Survey.","authors":"Kieran Connole, Olivia McDermott","doi":"10.1007/s43441-025-00812-z","DOIUrl":"10.1007/s43441-025-00812-z","url":null,"abstract":"<p><p>In the past decade, additive manufacturing has been applied to mainstream medical devices, particularly in the orthopaedic sector across the hip, knee and shoulder segments for implants and instruments. The research aimed to determine the level of knowledge regarding the regulatory requirements for additive manufactured devices in the Irish Orthopedic medical device sector as well as the challenges faced by orthopedic medical devices manufacturers in interpreting and implementing the current regulatory guidance in the US and the EU. The findings were that there is a lack of knowledge regarding additive manufacturing across the orthopaedic medical device sector and education is required to address this knowledge gap. Furthermore, while the United States has produced specific additive manufacturing guidance, many of the respondents surveyed stated that further clarity is required in this document to remove ambiguity and unclear interpretations of the document. However, in the European Union, there is no support for the use of additive manufacturing as no specific guidance has been provided. This is the first study of its kind on awareness of additive manufacturing regulations. The output of this research is that the Irish orthopaedic medical device sector needs to educate and support its sector members in gaining experience with additive manufacturing in order to ensure that these devices can be commercialised in a timely fashion.</p>","PeriodicalId":23084,"journal":{"name":"Therapeutic innovation & regulatory science","volume":" ","pages":"1160-1170"},"PeriodicalIF":1.9,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12446140/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144317918","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Overview of Orphan Medicines in European Union: An Analysis of Regulatory and Technical-Scientific Aspects.","authors":"Greta Santi Laurini, Victoria Nikitina, Massimiliano Broccoli, Nicola Montanaro, Domenico Motola","doi":"10.1007/s43441-025-00810-1","DOIUrl":"10.1007/s43441-025-00810-1","url":null,"abstract":"<p><strong>Introduction: </strong>The Orphan Medicinal Product Regulation was adopted in the EU in 2000 to encourage the implementation of medicines for rare diseases. Providing a current overview of its effects, this study was performed on medicines with active orphan designation authorised in the EU until January 17, 2024.</p><p><strong>Materials and methods: </strong>Based on the Community Register of orphan medicinal products for human use, active orphan designations of medicines that have been granted marketing authorisation (MA) were included in the study. General information on medicines, orphan designations, and MAs was collected from web-based sources and analysed using descriptive statistics.</p><p><strong>Results: </strong>Since 2000, 149 medicines with clinical indications with active orphan designation have been granted MA in the EU, making a total of 184 authorised orphan indications. Most medicines (96;64.4%) received standard MA, while 33 (22.1%) received conditional MA and 20 (13.4%) MA under exceptional circumstances. Sixty-five (43.6%) medicines were biological products, mainly monoclonal antibodies, recombinant human peptides or enzymes, or gene therapies. Active orphan designations with outcome for MA were primarily for indications for neoplasms or endocrine, nutritional or metabolic diseases. Orphan indications were licensed after a mean of 67.2 months (range 6-249 months) from designation date. For 93 (50.5%) orphan designations, the prevalence estimate of the condition in the EU was ≤ 1/10,000.</p><p><strong>Conclusions: </strong>Despite pharmacological advances, a limited number of orphan medicines have been authorised in the EU since the entry into force of the Orphan Regulation, making the lack of available medicines for rare diseases still a public health problem.</p>","PeriodicalId":23084,"journal":{"name":"Therapeutic innovation & regulatory science","volume":" ","pages":"1087-1097"},"PeriodicalIF":1.9,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12446149/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144174982","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cancer Clinical Trial Patients' Perceptions of Reporting Adverse Events Via an Electronic Platform.","authors":"Minna Grahvendy, Bena Brown, Laurelie R Wishart","doi":"10.1007/s43441-025-00804-z","DOIUrl":"10.1007/s43441-025-00804-z","url":null,"abstract":"<p><strong>Background: </strong>Accurate adverse event (AE) reporting is critical to the success of clinical trials; over the last 10 years, momentum has been building to collect AE data directly from the patient. In this study, we investigated the use of an electronic, web-based platform by which cancer clinical trial patients self-reported AE data. In this report, we explored the perceptions and experiences of participants using the platform during participation in an interventional clinical trial.</p><p><strong>Methodology: </strong>Patients consenting to an interventional clinical trial run by a cancer clinical trial unit at a tertiary hospital in Australia were eligible for enrolment. Participants used an online platform to report symptomatic data weekly over 26 weeks. Participant feedback on the platform was collected via an implementation survey at baseline, week 12, and week 26 and a qualitative interview at week 26.</p><p><strong>Results: </strong>Participants agreed that the platform was acceptable, appropriate, and feasible in its purpose. This agreement remained throughout their participation on the study. Qualitative analysis of interview data revealed three major themes: accessibility and useability, platform functionality, and personal attributes and benefits/burdens. Participants reported areas for improvement, primarily around platform functionality and consideration of symptom burden limiting participant capacity to engage with the platform.</p><p><strong>Conclusions: </strong>To our knowledge, this is the first study that investigates, in-depth, the participant experience of self-reporting cancer clinical trial AE data via an electronic platform. Our study lends evidence from the participant-perspective to previously-reported studies investigating the feasibility of collecting AE data directly from the patient. Participants agreed that the platform was feasible and would be of benefit to future cancer clinical trial participants.</p>","PeriodicalId":23084,"journal":{"name":"Therapeutic innovation & regulatory science","volume":" ","pages":"1064-1073"},"PeriodicalIF":1.9,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12446086/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144128811","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Analysis of Regulatory Botanical Submission Profile for Cancer Management from the U.S. FDA Perspectives.","authors":"Jin-Young K Park, Daniel Lee, Lixin Rui, Xiaoyue Gao, M Scott Furness, Charles Wu","doi":"10.1007/s43441-025-00786-y","DOIUrl":"10.1007/s43441-025-00786-y","url":null,"abstract":"<p><strong>Background: </strong>The United States Food and Drug Administration (FDA) has received over 700 botanical investigational new drug applications (INDs) in a broad spectrum of therapeutic areas since 1984. The greatest numbers were for cancer management. The aims of our study were to conduct a first-time, in-depth analysis of the regulatory submission profiles for botanical INDs with oncologic indications, in comparison with non-oncologic indications, and to share our regulatory review experience of oncologic botanical drug research and development.</p><p><strong>Methods: </strong>The FDA Center for Drug Evaluation and Research (CDER) maintains an in-house database of botanical INDs that contains many data elements, including initial 30-day actions (safe-to-proceed, clinical hold, etc.), current regulatory status, primary purpose of the proposed clinical trials, and initially proposed clinical trial phase information by sponsor. The database provided internally validated regulatory submission information that FDA received between March 1984 and December 2020 for 254 botanical INDs with oncologic indications, as well as 485 non-oncologic botanical INDs.</p><p><strong>Results: </strong>A higher percentage of the oncologic botanical INDs (69% versus 58% for non-oncologic botanical INDs, p < 0.01) received an initial 30-day safe-to-proceed designation to initiate the clinical investigations. One hundred thirty-seven oncologic botanical INDs were submitted to conduct phase 1 trials to investigate the safety and tolerability of their products, and 46 of these INDs are currently active. An additional 117 INDs were proposed to conduct phase 2 or phase 3 trials to assess safety and efficacy of oncologic botanical products, and 36 of those INDs are currently active, including 3 INDs in phase 3 trials. Most of the oncologic botanical INDs were for the investigation of specific solid tumors (71%) with more than one third of these related to prostate and breast tumors.</p><p><strong>Conclusions: </strong>Despite the scientific and regulatory challenges that FDA reviewers previously experienced, our analysis shows that there were over 80 currently active botanical oncologic INDs, including several in the late phase of drug development for cancer management. The implication of this finding is significant in that many clinical trials of botanical drug products intended to provide high-quality cancer patient care are in the regulatory pipeline.</p>","PeriodicalId":23084,"journal":{"name":"Therapeutic innovation & regulatory science","volume":" ","pages":"1129-1137"},"PeriodicalIF":1.9,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12446141/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144226724","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Leveraging Synthetic Data to Facilitate Research: A Collaborative Model for Analyzing Sensitive National Cancer Registry Data in England.","authors":"George Kafatos, Julia Levy, Sophie Jose, Pooja Hindocha, Olia Archangelidi, Sally Vernon, Lora Frayling","doi":"10.1007/s43441-025-00820-z","DOIUrl":"10.1007/s43441-025-00820-z","url":null,"abstract":"<p><p>Real-world data (RWD) are increasingly recognized as critical to advancing drug development and health care delivery, with regulatory bodies increasingly recognising their value. However, stringent governance requirements, while essential for protecting patient privacy, create significant challenges for conducting research. The Cancer Analysis System (CAS), managed by National Health Service (NHS) England, includes a national cancer registry and linked health care datasets. To address data access challenges, Simulacrum, a set of publicly available synthetic datasets generated from the CAS, can be used to carry out preliminary data analysis, hypothesis generation and development of programming code that can be executed to run analyses on CAS data. This paper presents a collaborative operating model that leverages Simulacrum to enable efficient, privacy-compliant analytics. Analysis of 18 projects conducted using this model demonstrated an average duration of 2.3 months from the start of Code Development to Data Release (CDDR). By enabling researchers to conduct privacy-compliant analysis on synthetic data, this approach increases transparency by providing insights into patient-level data while reduces reliance on custodians of sensitive data. Our findings highlight how synthetic data can be leveraged to facilitate efficient research on restricted patient-level RWD, while safeguarding patient privacy. This framework offers a scalable solution for other data custodians that can enable broader use of RWD, accelerating healthcare innovation.</p>","PeriodicalId":23084,"journal":{"name":"Therapeutic innovation & regulatory science","volume":" ","pages":"919-928"},"PeriodicalIF":1.9,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12446092/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144235267","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Navigating the Trends in USFDA Authorized Generic Approvals (2019-2024): Enhancing Healthcare Accessibility and Affordability.","authors":"M Sowndharya, Ramesh Joga, Kajal Gandhi, Gadekar Kailas Vijay, Sonali Waikar, Sravani Yerram, Rajeev Singh Raghuvanshi, Saurabh Srivastava","doi":"10.1007/s43441-025-00806-x","DOIUrl":"10.1007/s43441-025-00806-x","url":null,"abstract":"<p><strong>Objective: </strong>This study examines trends in USFDA's authorized generic (AG) approvals from January 2019 to August 2024, focusing on approval patterns, leading therapeutic areas, dominant dosage forms, and key companies. The research aims to highlight market dynamics and the role of AGs in enhancing healthcare accessibility and affordability with case studies.</p><p><strong>Methods: </strong>Data was collected from the FDA's list of authorized generic drugs and analyzed to identify trends in annual approvals, therapeutic areas, and dosage forms. A company-wise analysis was conducted to identify top performers, with a detailed evaluation of their approval trends and strategic focus areas across therapeutic categories. Recent case studies of AGs were included to explore their clinical and economic significance. The impact of the Inflation Reduction Act, Continuing Appropriations Act, of 2020, and Health Extenders Act of 2019 on the definition and pricing of AGs, as well as its implications for the pharmaceutical industry and Medicaid Drug Rebate Program, were examined.</p><p><strong>Results: </strong>AG approvals peaked in 2019 (31%) and 2020 (33%), then declined. Leading therapeutic areas were cardiovascular (18%), neurology (14%), and endocrinology (13%). Tablets comprised 35% of approvals, followed by capsules (23%) and solutions (9%). GlaxoSmithKline led with 7% of approvals, primarily in pulmonology and migraine, while Bausch Health (6.25%) focused on dermatology and endocrinology. IBSA Pharma (5.47%) excelled in endocrinology and pain management. Pfizer and Cediprof each had 4.69%, with Pfizer focusing on cardiovascular and infectious diseases, and Cediprof specializing in endocrinology. Recent case studies of AGs provided an affordable, effective alternative for diabetes and cardiovascular care.</p><p><strong>Conclusion: </strong>AGs effectively bridge the transition from branded to generic drugs, supporting broader access to treatment, cost efficiency, and ongoing innovation in the pharmaceutical sector. The analysis highlights AGs' significant role in addressing healthcare needs while underscoring challenges like exclusivity agreements and profit constraints for traditional generics. These findings affirm AGs as pivotal in advancing pharmaceutical market dynamics and healthcare affordability.</p>","PeriodicalId":23084,"journal":{"name":"Therapeutic innovation & regulatory science","volume":" ","pages":"1053-1063"},"PeriodicalIF":1.9,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144120925","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":"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":"929-931"},"PeriodicalIF":1.9,"publicationDate":"2025-09-01","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":"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":"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":"949-955"},"PeriodicalIF":1.9,"publicationDate":"2025-09-01","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":"Letter to the Editor \"Research on Core Competency Elements of Clinical Investigators\".","authors":"Sadia Farhana","doi":"10.1007/s43441-025-00815-w","DOIUrl":"10.1007/s43441-025-00815-w","url":null,"abstract":"","PeriodicalId":23084,"journal":{"name":"Therapeutic innovation & regulatory science","volume":" ","pages":"935-936"},"PeriodicalIF":1.9,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144182658","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}