Therapeutic innovation & regulatory science最新文献

{"title":"A Global Industry Survey on Post-Approval Change Management and Use of Reliance.","authors":"Andrew Deavin, Aliyah Hossain, Isabelle Colmagne-Poulard, Kum Cheun Wong, Mónica Perea-Vélez, Sonia Cappellini, Susanne Ausborn, Sylvie Meillerais, Céline Bourguignon","doi":"10.1007/s43441-024-00681-y","DOIUrl":"10.1007/s43441-024-00681-y","url":null,"abstract":"<p><p>Post-approval changes (PACs) to the control and manufacturing processes of medicines and vaccines are routinely undertaken and critical to enable both innovation and secure sustained supply. In a world of global supply chains, the existence of divergent national PAC requirements (with additional countries introducing new requirements with potential differences) and other factors including document preparation and response timelines, can lead to long delays in approval (of up to 3-5 years) increasing the risk of disruption and shortages.We undertook an Industry survey in 2023 to assess implementation of ICH Q12, PAC procedures (change categorisation and review timelines) and use of reliance mechanisms across different countries (9 selected ICH Members and 19 Observers). Although this survey revealed limited implementation of Q12 in ICH Member countries, when comparing the data collected with those of a previous survey performed in 2020, we observed a broader adoption of risk-based approaches to variation categorisation (in all countries). This, however, was not reflected in improved timelines for approval.With regards to ICH Q12 adoption, the uptake of Post-Approval Change Management Protocols (PACMPs) was unchanged (with only one country reporting in-use) and implementation gaps were evident for Established Conditions (EC) and the Product Life Cycle Management document (PLCM). The survey found greater awareness of ICH Q12 and its tools compared to 2020, potentially illustrating the positive impact of training efforts. This illustrates the challenges being faced to broaden its implementation and use globally.In the same Industry survey, we also assessed PAC processes across different international countries. Long unpredictable timelines were the major concern across the countries surveyed together with limited capacity of the regulators. Four different CMC changes were selected and categorized by the respondents according to current knowledge of national classifications and timelines in the selected countries and compared with a reference classification and timeline from the European Medicines Agency and the World Health Organisation. This highlighted the lack of harmonisation of many countries with EU/WHO requirements, especially within the ICH Observer group.Last, this survey showed that some use of unilateral forms of reliance to Reference Authorities for PACs is starting. This is a mechanism all countries can employ, regardless of convergence of requirements and expertise, to enhance capacity building and reduce duplication of reviews, streamline variations approval, whilst accelerating patient access to innovation and securing supply.</p>","PeriodicalId":23084,"journal":{"name":"Therapeutic innovation & regulatory science","volume":" ","pages":"1094-1107"},"PeriodicalIF":2.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142047248","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":"Publisher Correction: Capacity Assessment of the National Medicines Regulatory Authority in a Low -Income Country.","authors":"Fawzi Thomas, Onome T Abiri, Thomas A Conteh, Olufunsho Awodele","doi":"10.1007/s43441-024-00687-6","DOIUrl":"10.1007/s43441-024-00687-6","url":null,"abstract":"","PeriodicalId":23084,"journal":{"name":"Therapeutic innovation & regulatory science","volume":" ","pages":"1061"},"PeriodicalIF":2.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141902948","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":"Estimand Framework and Statistical Considerations for Integrated Analysis of Clinical Trial Safety Data.","authors":"Katarina Hedman, George Kordzakhia, Hongjian Li, Per Nyström","doi":"10.1007/s43441-024-00691-w","DOIUrl":"10.1007/s43441-024-00691-w","url":null,"abstract":"<p><strong>Background: </strong>Safety analyses play a pivotal role in drug development, ensuring the protection of patients while advancing innovative pharmaceuticals to market. A single study generally does not have sufficient sample size to evaluate all important safety events with reasonable precision and may not cover the full target population for the investigational treatment. Integrated analyses (pooled or meta-analysis) over several studies may be helpful in that regard. But without a structured conscious workflow accompanied with appropriate statistical methods for the integrated analysis, this can easily take a route compromising the interpretation.</p><p><strong>Methods: </strong>In this article we apply the ICH estimand framework to clinical trial integration and summarize respective critical statistical assumptions to ensure the integrated analyses are interpretable.</p><p><strong>Results: </strong>The estimand framework is valuable for developing principles for a deeper understanding of the critical statistical aspects of planning an integrated safety analysis. Our principles address the clinical question of interest, estimand and estimation. Special focus was given to the criteria for inclusion and exclusion of the component studies in the integrated analysis, and to integration of estimates pertaining to signal detection.</p><p><strong>Conclusion: </strong>Performing an integrated analysis and its preparatory steps calls for a good understanding of the clinical question of interest and its estimand, care and sound practice, to enable interpretation and avoid introducing unnecessary bias. It is valuable to use the estimand framework not only for efficacy evaluations, but also for safety evaluations in clinical trials and for integrated safety analyses.</p>","PeriodicalId":23084,"journal":{"name":"Therapeutic innovation & regulatory science","volume":" ","pages":"1120-1128"},"PeriodicalIF":2.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142112322","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":"Insights into Early Interactions on Innovative Developments with European Regulators.","authors":"David W Uster, Valentina Cordo', Emmanuel Cormier, Falk Ehmann","doi":"10.1007/s43441-024-00686-7","DOIUrl":"10.1007/s43441-024-00686-7","url":null,"abstract":"<p><strong>Introduction: </strong>The European Medicines Agency Innovation Task Force (ITF) acts as early point of contact for medicine and technology developers to enable innovation during early drug development stages through ITF briefing meetings.</p><p><strong>Aim: </strong>To reflect on the current pace of innovation and to assess the potential of ITF stakeholder interactions, a comprehensive analysis of the ITF briefing meetings held between 2021 and 2022 was conducted with a focus on individual questions raised by the developers and the related feedback provided by the European regulators.</p><p><strong>Methods: </strong>Questions raised during ITF briefing meetings were extracted and categorised into main and sub-categories, revealing different themes across the whole medicine development process such as manufacturing technologies, pre-clinical developments, and clinically relevant questions.</p><p><strong>Results: </strong>There was positive feedback from regulators who gave initial guidance in 85% of the answers, provided concrete examples in 20% of the answers and recommended to continue discussions through additional regulatory procedures in 22% of the answers.</p><p><strong>Conclusion: </strong>This analysis frames the content and the type of topics discussed during ITF briefing meetings. Moreover, it describes the type of regulatory feedback provided to medicine developers and identified potential for improvement of these early interactions. Therefore, this analysis emphasises the role of ITF briefing meetings in fostering innovation in medicine.</p>","PeriodicalId":23084,"journal":{"name":"Therapeutic innovation & regulatory science","volume":" ","pages":"1108-1119"},"PeriodicalIF":2.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11530471/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142112323","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":"Delta Inflation, Optimism Bias, and Uncertainty in Clinical Trials.","authors":"Charles C Liu, Peiwen Wu, Ron Xiaolong Yu","doi":"10.1007/s43441-024-00697-4","DOIUrl":"10.1007/s43441-024-00697-4","url":null,"abstract":"<p><p>The phenomenon of delta inflation, in which design treatment effects tend to exceed observed treatment effects, has been documented in several therapeutic areas. Delta inflation has often been attributed to investigators' optimism bias, or an unwarranted belief in the efficacy of new treatments. In contrast, we argue that delta inflation may be a natural consequence of clinical equipoise, that is, genuine uncertainty about the relative benefits of treatments before a trial is initiated. We review alternative methodologies that can offer more direct evidence about investigators' beliefs, including Bayesian priors and forecasting analysis. The available evidence for optimism bias appears to be mixed, and can be assessed only where uncertainty is expressed explicitly at the trial design stage.</p>","PeriodicalId":23084,"journal":{"name":"Therapeutic innovation & regulatory science","volume":" ","pages":"1180-1189"},"PeriodicalIF":2.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142146394","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":"Comparison of Product Features and Clinical Trial Designs for the DTx Products with the Indication of Insomnia Authorized by Regulatory Authorities.","authors":"Takashi Hosono, Yuki Niwa, Masuo Kondoh","doi":"10.1007/s43441-024-00684-9","DOIUrl":"10.1007/s43441-024-00684-9","url":null,"abstract":"<p><strong>Background: </strong>Digital therapeutics (DTx) have attracted attention as the substitutes or add-ons to conventional pharmacotherapy and the number of DTx products authorized with the regulatory reviews of the clinical evidence is increasing. Insomnia is one of the major targets of the DTx due to the benefit from cognitive behavioral interventions and several products have been launched in the market with regulatory reviews. However, common features of the products and the clinical evidence required by each regulatory agency have not been investigated.</p><p><strong>Methods: </strong>In this study, we identified the DTx products with the primary indication of insomnia authorized with regulatory reviews of clinical evidence by literature and website searches, and investigated the common features of the products and of the study designs for the pivotal clinical trials.</p><p><strong>Results: </strong>The total of 6 DTx products were identified. The components of cognitive behavioral therapy for insomnia (CBT-I) were identified as common features of the products. All the pivotal clinical trials were randomized, parallel-group, blind studies against insomnia patients. No products have been authorized in multiple countries regardless of the similarity of the features of the products and of the study designs for the pivotal clinical trials.</p><p><strong>Conclusions: </strong>Our study revealed that the components of CBT-I and gold standard design in pivotal clinical trials were adopted in all the DTx products for insomnia authorized with reviews of clinical evidence. At the same time, our findings suggest the needs of internationally harmonized regulatory review and authorization system to facilitate the early patient access to the promising DTx products.</p>","PeriodicalId":23084,"journal":{"name":"Therapeutic innovation & regulatory science","volume":" ","pages":"1138-1147"},"PeriodicalIF":2.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11530488/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142296139","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":"Mutagenic Azido Impurities in Drug Substances: A Perspective.","authors":"Sumit S Chourasiya, Deepika Kathuria, Vipin Kumar, Kamlesh J Ranbhan","doi":"10.1007/s43441-024-00675-w","DOIUrl":"10.1007/s43441-024-00675-w","url":null,"abstract":"<p><p>Contamination of drug products and substances containing impurities is a significant concern in the pharmaceutical industry because it may impact the quality and safety of medicinal products. Special attention is required when mutagenic impurities are present in pharmaceuticals, as they may pose a risk of carcinogenicity to humans. Therefore, controlling potential mutagenic impurities in active pharmaceutical ingredients to an acceptable safety limit is mandatory to ensure patient safety. As per the International Council for Harmonization (ICH) M7 (R2)³ Guideline, mutagenic impurities are those compounds or materials that induce point mutations. In 2018, the sartan class of drugs was recalled due to the presence of N-nitrosamine impurities, which are potential mutagens. In addition to the primary impurities being detected, this class of products, especially losartan, irbesartan and valsartan, have been identified as having organic azido contaminants, which are again highly reactive toward DNA, leading to an increased risk of cancer. These azido impurities form during the preparation of the tetrazole moiety via the reaction of a nitrile intermediate with sodium azide. Given that this is a newly raised issue in the pharmaceutical world, it should be noteworthy to review the related literature. Thus, this review article critically accounts for (i) the toxicity of azido impurities and the proposed mechanism of mutagenicity, (ii) the regulatory perspective, and (iii) the sources and control strategies used during the preparation of drug substances and (iv) future perspectives.</p>","PeriodicalId":23084,"journal":{"name":"Therapeutic innovation & regulatory science","volume":" ","pages":"1159-1171"},"PeriodicalIF":2.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141493521","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":"Adopting a Framework for Rapid Real-World Data Analyses in Safety Signal Assessment.","authors":"Lu Wang, Negar Golchin, Stephanie von Klot, Claudia A Salinas, Katrin Manlik, Vaishali Patadia, Mary K Miller, Julius Asubonteng, Rachel McDermott, Julie Barberio, Geoffrey Gipson","doi":"10.1007/s43441-024-00694-7","DOIUrl":"10.1007/s43441-024-00694-7","url":null,"abstract":"<p><p>The expanding availability of real-world data (RWD) has led to an increase in both the interest and possibilities for using this information in postmarketing safety analyses and signal management. While there is enormous potential value from the safety insights generated through RWD, the analysis preparation, execution, and communication required to reliably deliver the evidence can be time consuming. Since the safety signal assessment process is a regulated and timebound process, any supporting RWD analyses require a rapid turnaround of well-designed and informative results. To address this challenge, a TransCelerate BioPharma working group was formed and developed a framework to help teams responsible for safety signal assessment overcome the challenges of working with RWD rapidly to deliver analyses within regulatory timelines. Here, a previously performed safety assessment was evaluated within the context of the developed framework to illustrate how the framework may be adopted in practice.</p>","PeriodicalId":23084,"journal":{"name":"Therapeutic innovation & regulatory science","volume":" ","pages":"1014-1022"},"PeriodicalIF":2.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11530479/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142146393","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":"Pharmaceutical Company's Choices of Indication for the First Clinical Projects in Oncological Drug Development in the United States.","authors":"Can Wu, Shunsuke Ono","doi":"10.1007/s43441-024-00718-2","DOIUrl":"10.1007/s43441-024-00718-2","url":null,"abstract":"<p><p>We analyzed factors shaping the choice of the lead indication (i.e., cancer type) in the first clinical development projects of new oncological drugs in the United States (US), and how the type of pharmaceutical company is related to this choice. We selected 576 new clinical development projects in the US since 2000 for analysis. These projects were characterized according to three potential perspectives detected by multiple correspondence analysis: the morbidity of the cancer type which corresponds to market size of each cancer type, the company's previous experience with the cancer type, and the company's attitude to development risks. Mega firms tend to choose cancer types with higher morbidity (and large-market), previously experienced cancer types, while diverse small firms choose both major and rare cancers and both high- and low-risk projects, indicating that different sizes of firms utilize different development entry patterns. Common tendencies concerning the choice of lead indication were found across all companies. Cancer types the company had developed and launched in the past were more likely to be chosen; cancer types with high five-year survival rates and those with high competition were less likely to be chosen. The study showed that pharmaceutical companies seem to enter clinical development from cancer types where they can demonstrate their strengths and advantages through experience, depending on each cancer type's different market sizes and development difficulties. The results could provide clues for considering what support measures and incentives are appropriate to balance the efficiency of industrial development and the fulfillment of society's unmet medical needs.</p>","PeriodicalId":23084,"journal":{"name":"Therapeutic innovation & regulatory science","volume":" ","pages":""},"PeriodicalIF":2.0,"publicationDate":"2024-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142558862","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":"Expert Consensus Recommendations on a Biosimilars Value Framework for the Gulf Cooperation Council Countries.","authors":"Khalid A Alnaqbi, Ahmed Al-Jedai, Mohamed Farghaly, Mohammed A Omair, Anas Hamad, Fatemah M A Abutiban, Ali Al Shirawi, Hanan Al Rayes, Sarah Aldallal, Sahar Fahmy, Steven Simoens","doi":"10.1007/s43441-024-00716-4","DOIUrl":"https://doi.org/10.1007/s43441-024-00716-4","url":null,"abstract":"<p><strong>Objective: </strong>This paper aims to develop a biosimilar value framework with local stakeholders in Gulf Cooperation Council (GCC) countries.</p><p><strong>Methods: </strong>A convenience sample of ten key opinion leaders from the United Arab Emirates, Kingdom of Saudi Arabia, Kuwait, Oman and Qatar participated in an expert panel meeting in November 2022 that examined factors positively influencing biosimilar adoption in these countries. The discussion was structured around a conceptual biosimilar value framework and an overview of biosimilar policies as derived from a targeted review of the peer-reviewed and grey literature.</p><p><strong>Results: </strong>The expert panel agreed on a biosimilar value framework for the GCC countries that is founded on trust, cost savings and contextual considerations. They emphasized the importance of launching educational initiatives that build trust in and expand knowledge of all stakeholders about biosimilars. This also includes making stakeholders aware of the various value propositions of biosimilars as an instrument to produce, for example, cost savings. Finally, they stressed that biosimilar adoption is influenced by contextual factors such as incentives and implementation efforts.</p><p><strong>Conclusion: </strong>Our proposed biosimilars value framekwork is the first set of recommendations in the Arab countries designed to help policymakers and decision-makers promote biosimilar adoption, both in high-income GCC countries and in low- and middle-income countries.</p>","PeriodicalId":23084,"journal":{"name":"Therapeutic innovation & regulatory science","volume":" ","pages":""},"PeriodicalIF":2.0,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142547634","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}