Pharmaceutical Research最新文献_第3页

PBPK Modeling to Support Bioavailability and Bioequivalence Assessment in Pediatric Populations. PBPK模型支持儿科人群的生物利用度和生物等效性评估。

IF 3.5 3区医学

Pharmaceutical Research Pub Date : 2025-05-01 Epub Date: 2025-03-26 DOI: 10.1007/s11095-025-03846-y

Fang Wu, Eleftheria Tsakalozou, Gilbert J Burckart, Rebeka Žakelj, Lu Gaohua, Kazuko Sagawa, Viera Lukacova, Siva Vaithiyalingam, Jianghong Fan, Nikoletta Fotaki, Nikunjkumar Patel, Lanyan Fang

{"title":"PBPK Modeling to Support Bioavailability and Bioequivalence Assessment in Pediatric Populations.","authors":"Fang Wu, Eleftheria Tsakalozou, Gilbert J Burckart, Rebeka Žakelj, Lu Gaohua, Kazuko Sagawa, Viera Lukacova, Siva Vaithiyalingam, Jianghong Fan, Nikoletta Fotaki, Nikunjkumar Patel, Lanyan Fang","doi":"10.1007/s11095-025-03846-y","DOIUrl":"10.1007/s11095-025-03846-y","url":null,"abstract":"This report summarizes the proceedings for Session 3 of the one-day public workshop entitled \"Advances in PBPK Modeling and its Regulatory Utility for Oral Drug Product Development\" a jointly sponsored workshop by U.S. Food and Drug Administration (FDA) and the Center for Research on Complex Generics (CRCG) on October 12, 2023. The theme of this session was the application and relevant considerations for PBPK modeling in supporting bioavailability (BA) and BE assessment in pediatric populations. The takeaway message from this session was that PBPK modeling can support relative BA and BE assessment in pediatrics since such studies are generally performed in adults or healthy subjects. PBPK absorption modeling can incorporate characteristics of the drug substance and formulation as well as pediatric physiology to assess the potential differences in absorption of different formulations in pediatrics for new and generic drugs. It is necessary to consider the totality of data and use all available evidence integrated into a mechanistic PBPK model to support decision-making. Global research efforts are needed to bridge critical data gaps.","PeriodicalId":20027,"journal":{"name":"Pharmaceutical Research","volume":" ","pages":"847-855"},"PeriodicalIF":3.5,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12158840/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143720971","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Immunogenicity of Generic Peptide Impurities: Current Orthogonal Approaches. 通用肽杂质的免疫原性：目前的正交方法。

IF 3.5 3区医学

Pharmaceutical Research Pub Date : 2025-05-01 Epub Date: 2025-03-24 DOI: 10.1007/s11095-025-03843-1

Anne S De Groot, Aimee Mattei, Benjamin Gabriel, Jennifer Calderini, Brian J Roberts, Sandra Lelias, Mitchell McAllister, Christine Boyle, William Martin, Guilhem Richard

{"title":"Immunogenicity of Generic Peptide Impurities: Current Orthogonal Approaches.","authors":"Anne S De Groot, Aimee Mattei, Benjamin Gabriel, Jennifer Calderini, Brian J Roberts, Sandra Lelias, Mitchell McAllister, Christine Boyle, William Martin, Guilhem Richard","doi":"10.1007/s11095-025-03843-1","DOIUrl":"10.1007/s11095-025-03843-1","url":null,"abstract":"Generic drugs have saved consumers billions of dollars in the United States. The demand for lower-cost and effective drugs, particularly for well-known peptide drugs like Ozempic and Wegovy (brand names for semaglutide), has resulted in a surge of generic drug development to address perceived shortages in the supply of the reference listed drugs (RLD). To address this demand for generics and expedite consumer access to lower-cost generic versions of approved drugs, the U.S. Food and Drug Administration (FDA) has developed an \"Abbreviated New Drug Application\" (ANDA) pathway that simplifies the generic drug review process and expands access to these much-needed medicines without compromising quality and safety standards. Guidelines for this pathway require sponsors to identify and characterize both process- and product-related impurities in drug formulations that differ in nature or concentration from the RLD. The ANDA pathway devotes specific attention to immunogenicity and recommends the use of orthogonal methods of assessment to demonstrate that a proposed generic drug is immunologically equivalent to its RLD and therefore suitable for submission via the ANDA pathway. In this perspective, we describe several orthogonal methods for immunogenicity risk assessment of generic peptide impurities and contrast these with other methods such as MHC-Associated Peptide Proteomics peptide elution (MAPPs) assays. Given their importance in the generic drug approval pathway, we have submitted the \"PANDA®\" immunogenicity risk assessment methods as a 'model master file'.","PeriodicalId":20027,"journal":{"name":"Pharmaceutical Research","volume":" ","pages":"805-818"},"PeriodicalIF":3.5,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12159091/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143701146","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Considering Opportunities and Challenges When Implementing the Model Master File Framework - a Meeting Report. 实施模型主文件框架时的机遇与挑战——会议报告。

IF 3.5 3区医学

Pharmaceutical Research Pub Date : 2025-05-01 Epub Date: 2025-03-07 DOI: 10.1007/s11095-025-03839-x

Eleftheria Tsakalozou, Lanyan Fang, Erin Skoda, Timothy Nicholas, Sivacharan Kollipara, Ke Ren, Stella Grosser, Bhagwant Rege, Partha Roy, Hao Zhu, Liang Zhao

引用次数: 0

Assessing Impact of Food on Oral Drug Bioequivalence Supporting ICH M13 A with the Advancements of Physiologically Based Pharmacokinetic Modeling. 基于生理药代动力学模型的进展评估食品对支持ICH m13a的口服药物生物等效性的影响。

IF 3.5 3区医学

Pharmaceutical Research Pub Date : 2025-05-01 Epub Date: 2025-06-04 DOI: 10.1007/s11095-025-03866-8

Arindom Pal, Khondoker Alam, Ethan Stier, Tycho Heimbach, Rodrigo Cristofoletti, Jozef Al-Gousous, Peter Langguth, Rebeka Žakelj, Tausif Ahmed, Susana Almeida, Jianghong Fan, Vidula Kolhatkar, Paulo Paixão, Mohan Krishna Rayeni, Lei Zhang, Fang Wu

{"title":"Assessing Impact of Food on Oral Drug Bioequivalence Supporting ICH M13 A with the Advancements of Physiologically Based Pharmacokinetic Modeling.","authors":"Arindom Pal, Khondoker Alam, Ethan Stier, Tycho Heimbach, Rodrigo Cristofoletti, Jozef Al-Gousous, Peter Langguth, Rebeka Žakelj, Tausif Ahmed, Susana Almeida, Jianghong Fan, Vidula Kolhatkar, Paulo Paixão, Mohan Krishna Rayeni, Lei Zhang, Fang Wu","doi":"10.1007/s11095-025-03866-8","DOIUrl":"10.1007/s11095-025-03866-8","url":null,"abstract":"On October 12, 2023, the U.S. Food and Drug Administration (FDA) and the Center for Research on Complex Generics (CRCG) hosted a public workshop on \"Advances in PBPK Modeling and its Regulatory Utility for Oral Drug Product Development\", which highlighted significant strides in physiologically based pharmacokinetic (PBPK) modeling, particularly its application in the regulatory decision-making processes. This manuscript provides a comprehensive overview from the second session of the workshop titled \"PBPK Modeling to Evaluate Food Impact on Bioequivalence Supporting ICH M13A\", focusing on the critical role of PBPK modeling to evaluate the influence of food on drug bioequivalence (BE). Presentations and panel discussions from this session addressed the application of PBPK modeling for potential biowaiver of certain fed BE studies, thereby enhancing drug development efficiency and reducing costs. Presented case studies highlighted that PBPK modeling can be used to recapitulate formulation-dependent food impact, assist in the selection of biopredictive dissolution method and provide support for justifying the waiver of fed BE studies. The discussions also explored advanced methodologies for simulating the gastrointestinal environment more accurately and the operational insights from companies integrating PBPK modeling into their drug development program. Challenges such as the need for robust model validation and the integration of biopredictive dissolution testing results into the PBPK model were emphasized. Overall, the workshop session underscored the burgeoning confidence in PBPK modeling as a tool to refine regulatory pathways and optimize drug product evaluations, support future advancements in the field and harmonization across different regulatory agencies.","PeriodicalId":20027,"journal":{"name":"Pharmaceutical Research","volume":" ","pages":"835-845"},"PeriodicalIF":3.5,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144226275","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Advances in Physiologically Based Pharmacokinetic (PBPK) Modeling and its Regulatory Utility to Support Oral Drug Product Development and Harmonization. 基于生理的药代动力学（PBPK）建模及其支持口服药物产品开发和协调的监管效用研究进展。

IF 3.5 3区医学

Pharmaceutical Research Pub Date : 2025-05-01 Epub Date: 2025-03-28 DOI: 10.1007/s11095-025-03849-9

Yi-Hsien Cheng, Sherin Thomas, Yu Chung Tsang, Susana Almeida, Muhammad Ashraf, Nikoletta Fotaki, Tycho Heimbach, Nikunjkumar Patel, Harshil Shah, Xiaojian Jiang, Myong-Jin Kim, Rebecca Moody, Amin Rostami-Hodjegan, Romi Singh, Liang Zhao, Andrew Babiskin, Fang Wu

{"title":"Advances in Physiologically Based Pharmacokinetic (PBPK) Modeling and its Regulatory Utility to Support Oral Drug Product Development and Harmonization.","authors":"Yi-Hsien Cheng, Sherin Thomas, Yu Chung Tsang, Susana Almeida, Muhammad Ashraf, Nikoletta Fotaki, Tycho Heimbach, Nikunjkumar Patel, Harshil Shah, Xiaojian Jiang, Myong-Jin Kim, Rebecca Moody, Amin Rostami-Hodjegan, Romi Singh, Liang Zhao, Andrew Babiskin, Fang Wu","doi":"10.1007/s11095-025-03849-9","DOIUrl":"10.1007/s11095-025-03849-9","url":null,"abstract":"This report summarizes the proceedings of Session 1 of the one-day public workshop titled \"Advances in PBPK Modeling and its Regulatory Utility for Oral Drug Product Development\" hosted by the U.S. Food and Drug Administration (FDA) and the Center for Research on Complex Generics (CRCG) on October 12, 2023. This report focuses on cutting-edge developments, ongoing challenges, and potential solutions in the field of physiologically based pharmacokinetic (PBPK) absorption modeling for systemic and gastrointestinal (GI) locally acting oral drug products, as well as exploring opportunities to enhance global harmonization for generic drug development. Despite significant advancements and several successful case studies of utilizing PBPK models in generic drug development, developing patient-centric dissolution quality standards using PBPK modeling that account for food effects or different disease states remains challenging. Combining multiple dissolution studies at different pH ranges can aid in developing patient-centric dissolution specifications. Additionally, a major challenge for GI locally acting drug products is the inability to validate the PBPK model for local bioavailability due to the lack of measured data for local drug concentration along the different sections of the GI tract. A totality of evidence-based approach, taking account of all available data in addition to PBPK modeling-based evidence, should be considered. Moving forward, it is crucial to promote global collaboration and research by sharing knowledge and experiences for utilizing PBPK models in regulatory contexts to advance both internal and international harmonization.","PeriodicalId":20027,"journal":{"name":"Pharmaceutical Research","volume":" ","pages":"819-833"},"PeriodicalIF":3.5,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12158835/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143742562","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Adopting the Model Master File Framework to Enhance Modeling and Simulations Approaches for Regulatory Use. 采用模型主文件框架以增强监管使用的建模和仿真方法。

IF 3.5 3区医学

Pharmaceutical Research Pub Date : 2025-05-01 Epub Date: 2025-06-03 DOI: 10.1007/s11095-025-03861-z

Lanyan Fang, Eleftheria Tsakalozou, Fang Wu, Daniel Ritterbeck, Liang Zhao, Lei Zhang, Robert Lionberger

{"title":"Adopting the Model Master File Framework to Enhance Modeling and Simulations Approaches for Regulatory Use.","authors":"Lanyan Fang, Eleftheria Tsakalozou, Fang Wu, Daniel Ritterbeck, Liang Zhao, Lei Zhang, Robert Lionberger","doi":"10.1007/s11095-025-03861-z","DOIUrl":"10.1007/s11095-025-03861-z","url":null,"abstract":"This overview summarizes the history and advancements of the modeling and simulation programs utilized in drug development and regulatory assessment, including the FDA's Model-Informed Drug Development (MIDD) Paired Meeting Program and the Model-Integrated Evidence (MIE) Meeting Pilot Between FDA and Generic Drug Applicants. The U.S. Food and Drug Administration's (FDA) recent notice concerning the use of the Type V Drug Master File (DMF) for Model Master File (MMF) submissions to support abbreviated new drug applications (ANDAs) encourages and facilitates model-sharing and model-reusability in drug development, supporting MIE programs using a broad range of quantitative models, including, but not limited to physiologically based pharmacokinetic (PBPK), population pharmacokinetics (PPK) and computational fluid dynamics (CFD) modeling. This overview also introduces the considerations and representative mock examples of MMFs discussed in the workshop titled \"Considerations and Potential Regulatory Applications for a Model Master File (MMF)\" co-hosted by the U.S. Food and Drug Administration (FDA) and the Center for Research on Complex Generics (CRCG) on May 2-3, 2024. MMFs promote modeling and simulation approaches by reducing the burden of resources in developing this type of approaches for the pharmaceutical industry while increasing consistency and efficiency in regulatory assessments.","PeriodicalId":20027,"journal":{"name":"Pharmaceutical Research","volume":" ","pages":"731-735"},"PeriodicalIF":3.5,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144216564","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Leveraging Model Master Files for Long-Acting Injectables. 利用模型主文件进行长效注入。

IF 3.5 3区医学

Pharmaceutical Research Pub Date : 2025-05-01 Epub Date: 2025-01-28 DOI: 10.1007/s11095-025-03824-4

Yuqing Gong, Robert Hopefl, Tonglei Li, Andrew C Hooker, Daniela Amaral Silva, Khondoker Alam, Murray Ducharme, Rebecca Moody, Pratik Saha, Andrew Babiskin

{"title":"Leveraging Model Master Files for Long-Acting Injectables.","authors":"Yuqing Gong, Robert Hopefl, Tonglei Li, Andrew C Hooker, Daniela Amaral Silva, Khondoker Alam, Murray Ducharme, Rebecca Moody, Pratik Saha, Andrew Babiskin","doi":"10.1007/s11095-025-03824-4","DOIUrl":"10.1007/s11095-025-03824-4","url":null,"abstract":"The U.S. Food and Drug Administration (FDA) and the Center for Research on Complex Generics (CRCG) hosted a public workshop on May 2-3, 2024, titled \"Considerations and Potential Regulatory Applications for a Model Master File\". The workshop aimed to discuss the application of the Model Master File (MMF) concept in regulatory submissions that contain model integrated evidence (MIE), improving model sharing, model standardization, regulatory consistency, and regulatory efficiency. On Day 1, there was a session dedicated to MMF applications for long-acting injectables (LAIs). This perspective summarizes presentations, panel discussion, and small group discussion for the potential applications of MMFs in LAI product development, including case studies and potential situations in which MMFs can support regulatory submissions. The scientific presentations discussed the application of MMFs in mechanistic physiologically based pharmacokinetic (PBPK), multiphysics simulation, and population pharmacokinetics (popPK) models, as well as the potential utility of a model-integrated bioequivalence (MI-BE) framework. Additionally, challenges and considerations of implementing MMFs for LAIs were discussed in the panel and small groups. The anticipated benefits of MMFs are recognized among model developers, industries, and regulators.","PeriodicalId":20027,"journal":{"name":"Pharmaceutical Research","volume":" ","pages":"747-752"},"PeriodicalIF":3.5,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12159082/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143060103","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Regulatory and Industry Perspective on the Model Master File Framework for Locally Acting Drug Products. 监管和行业对本地作用药品模型主文件框架的看法。

IF 3.5 3区医学

Pharmaceutical Research Pub Date : 2025-05-01 Epub Date: 2025-02-26 DOI: 10.1007/s11095-025-03823-5

Ross L Walenga, Khondoker Alam, James F Clarke, Jan De Backer, Markus Fridén, Abdullah Hamadeh, Jay Mowli, Sujatha Sonti, Jessica Spires, Ming-Liang Tan, Flora T Musuamba, Eleftheria Tsakalozou

引用次数: 0

Combining High-Throughput Screening and Machine Learning to Predict the Formation of Both Binary and Ternary Amorphous Solid Dispersion Formulations for Early Drug Discovery and Development. 结合高通量筛选和机器学习预测二元和三元非晶固体分散配方的形成，用于早期药物发现和开发。

IF 3.5 3区医学

Pharmaceutical Research Pub Date : 2025-04-01 Epub Date: 2025-04-03 DOI: 10.1007/s11095-025-03853-z

Tianshu Lu, Yiyang Wu, Ping Xiong, Hao Zhong, Yang Ding, Haifeng Li, Defang Ouyang

{"title":"Combining High-Throughput Screening and Machine Learning to Predict the Formation of Both Binary and Ternary Amorphous Solid Dispersion Formulations for Early Drug Discovery and Development.","authors":"Tianshu Lu, Yiyang Wu, Ping Xiong, Hao Zhong, Yang Ding, Haifeng Li, Defang Ouyang","doi":"10.1007/s11095-025-03853-z","DOIUrl":"10.1007/s11095-025-03853-z","url":null,"abstract":"Objective: Amorphous solid dispersion (ASD) is widely utilized to enhance the solubility and bioavailability of water-insoluble drugs. However, conventional experimental approaches for ASD development are often resource-intensive and time-consuming. Machine learning (ML) algorithms have great potential to predict ASD formulations but face the challenge of extensive data to construct reliable models. Current study aims to predict the formation of both binary and ternary ASD by combined high-throughput screening (HTS) and ML approaches.Methods: Micro-quantity HTS was conducted to generate 1272 binary and ternary solid dispersions using solvent evaporation method. The Powder X-Ray Diffraction (PXRD) was used to characterize the amorphous state of formulations. The results indicated that 188 formulations successfully formed amorphous solid dispersions (ASDs), while 1084 resulted in crystalline formations. Models development employed nested cross-validation with four algorithms: Light Gradient Boosting Machine (LGBM), Random Forest (RF), Support Vector Machine (SVM), and Multi-Layer Perceptron (MLP).Results: The RF model for ASD formation achieved 96.7% accuracy on the in-house HTS dataset, with a precision of approximately 87.9% and an F1 score of 83.6%. Furthermore, the RF model trained with milligram-scale HTS experimental data could effectively predict the large-scale ASD formulations from the literature, highlighting its promise as a powerful tool for advancing ASD prediction.Conclusion: In summary, the combination of HTS experiments and ML techniques provides a valuable reference framework for ASD development, greatly minimizing both time and material usage in the selection of formulations during the early stages of drug discovery with a limited quantity of API.","PeriodicalId":20027,"journal":{"name":"Pharmaceutical Research","volume":" ","pages":"697-709"},"PeriodicalIF":3.5,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143780826","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Correction: A Preformulation Experiment: The Influence of Poloxamer 188 and Poloxamer 407 on the Binding Coefficients (Single Molecule) and the Partitioning Coefficients (Micelle) of Ketoprofen (Probe Molecule) with Sodium Cholate, Dodecyl Trimethylammonium Bromide and BrijC10 Surfactants. 修正：一个预处方实验：poloxam188和poloxam407对酮洛芬（探针分子）与胆酸钠、十二烷基三甲基溴化铵和BrijC10表面活性剂结合系数（单分子）和分配系数（胶束）的影响。

IF 3.5 3区医学

Pharmaceutical Research Pub Date : 2025-04-01 DOI: 10.1007/s11095-025-03862-y

Zita Farkaš Agatić, Vesna Tepavčević, Mladena Lalić-Popović, Nemanja Todorović, Ana Stjepanović, Mihalj Poša

引用次数: 0