The AAPS Journal

American Association of Pharmaceutical Scientists (AAPS) | @aapscomms #AAPSjournal

Lamotrigine (LTG) is commonly used as monotherapy and in combination with sodium valproate (VPA). The clinical drug-drug interaction (DDI) between LTG and VPA results in increased systemic exposure to lamotrigine in a dose-dependent manner with VPA. But what drives this interaction? A recent AAPS journal paper sheds new light on this. It demonstrates that UGT2B10 is the key UGT2B enzyme involved in the N2-glucuronidation of lamotrigine. The study suggests that the DDI between LTG and VPA is likely caused by the inhibition of this UGT2B10-mediated pathway in vivo. Read the full article at the following link: https://lnkd.in/gvJpbJsp Lloyd Wei Tat Tang Kimberly Lapham Theunis Goosen #aapsjournal?#DrugInteractions #Lamotrigine #ValproicAcid #UGT2B10 American Association of Pharmaceutical Scientists (AAPS) | @aapscomms

A "Hot Topic" session was convened at the 2023 AAPS PharmSci 360 conference (October 2023, Orlando, FL) to explore the challenges and considerations surrounding its implementation. This report provides a comprehensive summary of the key insights and discussions from the ICH M10 session. If you couldn’t attend AAPS 2023, you can catch up on the key discussions by reading the open summary article here: https://lnkd.in/gwykb6VY Faye V. Enaksha Wickremsinhe, Ph.D. Eric Woolf Chongwoo Yu American Association of Pharmaceutical Scientists (AAPS) | @aapscomms #aapsjournal? #ICHM10 #BioanalyticalMethods #AAPSPharmSci360 #PharmSci #ConferenceRecap

I am excited to announce the publication of our white paper on the use of enzymatic assays in bioanalysis in AAPS Journal this week! The paper provides an introduction to different types of applications for use in these assessments, considers the diversity of design, explores variables that impact robustness, discusses considerations for fit for purpose validations, and concludes with a discussion of life cycle management principles. As the use of these assays has increased in recent years with the influx of interest in CGT programs, this paper aims to provide background on how scientists across the industry are approaching these assays and to provide a framework for assay development and validation that can inform future work and alignment in the field--as well as share information about how bioanalytical scientists can boost consistency and reproducibility of enzymatic measurements. Link to article: https://lnkd.in/ex4q5a_K Springer Full text link: https://rdcu.be/dRQsz I want to highlight all of the amazing authors from across the industry who worked together to complete this project: Mitra Azadeh; Jeremy Good; Michele Gunsior (she/her); Nadia Kulagina; Yanmei Lu; Jim McNally; Heather Myler; Yan G. Ni; Ryan Pelto; Karen Quadrini; Lin Yang. Authorship is presented in alphabetical order. I also want to thank Heather Myler for her leadership in giving me the opportunity to coordinate this initiative, which was very generous and allowed me to develop new skills and perspectives. I learned a lot from the co-authors who had experiences in, for example, kinetic assay development and in ERT (as opposed to gene therapy) applications. I welcome all to check out the manuscript as well as the rest of the special issue/series "Emerging Trends in Preclinical and Clinical Development of Cell and Gene Therapies" in AAPS Journal.

Current treatments for inherited enzyme deficiencies include enzyme replacement therapy and small molecule chaperones, with gene and cell therapies showing promising potential. Enzyme activity assays play a crucial role in disease diagnosis, drug efficacy evaluation, and therapeutic development. This AAPS review explores the technical aspects of enzyme assays, including their design, validation, and life cycle management. Read this article at: https://lnkd.in/g-RmywVJ #biotech #enzymetherapy #genetherapy #drugdevelopment #aapsjournal? @aapscomms Mitra Azadeh Jeremy Good Michele Gunsior (she/her) Nadia Kulagina Yanmei Lu Jim McNally Heather Myler Yan G. Ni Ryan Pelto Karen J. Quadrini Catherine Vrentas & Lin Yang

The Generic Drug User Fee Amendments (GDUFA) aim to bring more affordable generic drugs to market, reducing costs for consumers and easing the regulatory burden on manufacturers. Since its implementation, first-cycle approvals have significantly improved, reflecting GDUFA's positive impact on the FDA's review process. While the FDA doesn't control drug pricing, GDUFA II set out to ensure timely approval of first generics, which is crucial for increasing competition and accessibility in the market. The research published in AAPS journal examines the effectiveness of changes made during GDUFA's first transition period, focusing on how these shifts have influenced the approval process for original ANDAs. Read this article at:?https://lnkd.in/gcN9q4ey @Erica Friedman Leah W. Falade, Ph.D. @Michael G. Bartlett American Association of Pharmaceutical Scientists (AAPS) | @aapscomms #GenericDrugs #GDUFA #aapsjournal?

Oral medications are preferred for their ease of use, convenience, and high patient compliance. However, certain groups, such as the elderly, children, and those with conditions like Parkinson's, may have difficulty swallowing traditional tablets and capsules. Oral thin films (OTFs) offer a solution by dissolving quickly in the mouth, making them ideal for delivering various medications. While promising, OTFs face challenges like sensitivity to humidity and limited drug capacity. Understanding drug-polymer interactions is key to optimizing these formulations. The complex interactions between the drug, counter acids, and polymers must be carefully managed. This AAPS journal article explores how these interactions affect miscibility and provides insights for better design: https://lnkd.in/gPt83amq? @Jie Liu @Yongguo Zhang @Chao Liu @Lian Fang @aapscomms #DrugDelivery #OTFs #aapsjournal?

The AAPS Journals Make Use of Portable Peer Review https://lnkd.in/g8Pf-kyh

Immunogenicity testing is crucial for understanding the immune response to protein therapeutics. Detection of neutralizing antibodies (NAb) involves various assays, from simple ligand binding to complex cell-based tests. The presentation of NAb assay results varies due to different mechanisms of action and functional domains of the drugs. Unique aspects, such as assay format, platform, critical reagents, and sensitivity estimation, add to the complexity. Harmonized reporting of these results is beneficial for consistency across the industry. Find several references as examples of how to assess neutralizing antibody activity in the context of safety, PK, and PD, which is critical for the study CSR or ISI in the recent AAPS journal’s white paper titled “Neutralizing Antibody Sample Testing and Report Harmonization”, authored by Darshana Jani Michele Gunsior (she/her) Robin Marsden Kyra Cowan Susan Irvin, PhD, PMP Laura Schild Hay Bethany Ward Luke Armstrong Mitra Azadeh Liching Cao, Rebecca Carmean, Jason DelCarpini, Sanjay Dholakiya, Amanda Hays, PhD, Sarah Hosback, Zheng Hu, Nadia Kulagina, Seema K. , Ching Ha Lai, @Marit Lichtfuss, Hsing-Yin Liu, Susana Liu, PMP, MSc, Reza Mozaffari, Luying Pan, Jason Pennucci, Marie-Eve Poupart, Gurleen Saini, Veerle Snoeck, @Kristine Storey, @Amy Turner, Inna Vainshtein, Daniela Verthelyi, Iwona Wala, Lili Yang Lin Yang. https://lnkd.in/gdr7jUth #Immunogenicity #NeutralizingAntibodies #ProteinTherapeutics #aapsjournal American Association of Pharmaceutical Scientists (AAPS) | @aapscomms

Establishing an In Vitro-In Vivo Correlation (IVIVC) model is crucial in pharmaceutical development as it helps to bridge the gap between in vitro drug release testing and in vivo drug absorption. The combination of IVIVC and PBPK modelling provides a powerful tool for predicting drug behaviour, optimizing formulations, and ultimately improving patient outcomes. It enables more precise forecasts of drug behavior within the body, leading to well-informed decisions in drug formulation and optimization. Discover the assessment criteria for generic omeprazole enteric-coated capsules, established with omeprazole's IVIVR based on the PBPK model in the AAPS Journal publication titled "Establishing Virtual Bioequivalence and Clinically Relevant Specifications for Omeprazole Enteric-Coated Capsules by Incorporating Dissolution Data in PBPK Modeling," authored by. Learn about evaluation criteria for generic omeprazole enteric-coated capsules established with omeprazole’s IVIVR based on the PBPK model in the aaps journal publication titled “Establishing Virtual Bioequivalence and Clinically Relevant Specifications for Omeprazole Enteric-Coated Capsules by Incorporating Dissolution Data in PBPK Modeling”, authored by? Ruwei Yang,?Yaqi Lin,?Kaifeng Chen,?Jie Huang,?Shuang Yang,?An Yao,?Xiaoyan Yang,?Deqing Lei,?Jing Xiao,?Guoping Yang?&?Qi Pei? https://lnkd.in/gZgsAnea American Association of Pharmaceutical Scientists (AAPS) | @aapscomms