Journal of pharmaceutical sciences最新文献

{"title":"Comparative analysis of empty and full adeno-associated viruses under stress conditions by anion-exchange chromatography, analytical ultracentrifugation, and mass photometry","authors":"Julia A. Townsend ,&nbsp;Shuai Li ,&nbsp;Laura Sweezy ,&nbsp;Nina Liu ,&nbsp;Michael P. Rosconi ,&nbsp;Erica A. Pyles ,&nbsp;Li Zhi ,&nbsp;Dingjiang Liu ,&nbsp;Zhijie Wu ,&nbsp;Haibo Qiu ,&nbsp;Mohammed Shameem ,&nbsp;Ning Li","doi":"10.1016/j.xphs.2025.01.005","DOIUrl":"10.1016/j.xphs.2025.01.005","url":null,"abstract":"<div><div>Adeno-associated viruses (AAVs) have emerged as a promising gene delivery vehicle for the treatment of diseases. As AAVs are a complex therapeutic modality, new analytical techniques are needed to thoroughly characterize the critical quality attributes (CQAs) to support drug development. Empty and full ratio is one of the CQAs of AAVs that may impact drug safety and efficacy. While the empty and full ratio of AAV therapeutics in untreated conditions can be well characterized by different analytical methods, limited studies have demonstrated whether these analytical methods can be used for characterizing stressed AAVs, which can help with assessing the stability of the molecule and identify potential degradation pathways. Here, we employ three orthogonal analytical techniques — (1) anion-exchange chromatography (AEX), (2) analytical ultracentrifugation (AUC), and (3) recently introduced mass photometry (MP) — to investigate their ability to characterize AAV samples subjected to various stress conditions, including freeze/thaw, physical agitation, and thermal stress. Based on our observations, AEX is a high-throughput technique. However, it falls short in quantifying the amount of partially filled AAVs, and the quantification is significantly impacted by post-translational modifications, which often occur to AAVs under stress conditions. AUC provides the best resolution for stressed AAV samples but is limited by its throughput and high sample consumption. MP combines the strength of being high-throughput and requires the least amount of samples, albeit at the expense of lower resolution compared to AUC. Our study suggests that each of these three techniques, AEX, AUC, and the emerging MP method, is suitable for characterizing empty and full AAV particles at various stages throughout the lifecycle of drug development.</div></div>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":"114 2","pages":"Pages 1237-1244"},"PeriodicalIF":3.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143006646","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}

{"title":"Bioequivalence requirements for orally inhaled and nasal drug products and use of novel physiologically based biopharmaceutics modeling approaches for assessing in vivo performance","authors":"Aravind Rachapally,&nbsp;Rajkumar Boddu,&nbsp;Sivacharan Kollipara,&nbsp;Tausif Ahmed","doi":"10.1016/j.xphs.2024.10.009","DOIUrl":"10.1016/j.xphs.2024.10.009","url":null,"abstract":"<div><div>Orally inhaled and nasal drug products (OINDPs) are complex due to the interplay between the device, formulation, and patient characteristics. Establishing bioequivalence (BE) of OINDPs with reference is highly complex and require <em>in vitro, in vivo</em> pharmacokinetic and comparative clinical endpoint studies that are challenging to conduct. In order to increase the rate of submission and approval of generics, regulatory agencies are encouraging the use of alternative <em>in vitro</em> and <em>in silico</em> methodologies to replace complex <em>in vivo</em> studies. The present review attempts to summarize current understanding of alternative BE approaches for OINDPs. <em>In vitro</em> characterization studies required for establishing BE for OINDPs considering USFDA and EMA guidance's are detailed. <em>In silico</em> models such as pulmonary compartmental absorption and transit (PCAT) with emphasis on model input parameters are portrayed. Further, two detailed case studies of inhalation nebulizer and nasal spray formulations are described where PCAT models are developed for predicting BE and local concentrations. Lastly, current understanding of such BE approaches from regulatory perspectives are discussed summarizing recent regulatory workshops and through collation of USFDA product specific guidance's for almost 70 drug products. Overall, this manuscript can act as ready-to-use guide to understand alternative approaches for establishing BE for OINDPs.</div></div>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":"114 2","pages":"Pages 701-718"},"PeriodicalIF":3.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142468268","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}

{"title":"Kinetics of the inhibition of CYP3A4 and CYP2C19 activity by jabara juice and identification of the responsible inhibitory components","authors":"Kana Koinuma ,&nbsp;Kenji Noto ,&nbsp;Tokio Morita ,&nbsp;Yoshinori Uekusa ,&nbsp;Haruhisa Kikuchi ,&nbsp;Miyuki Shimoji ,&nbsp;Hiroyuki Seki ,&nbsp;Hiroshi Yamazaki ,&nbsp;F. Peter Guengerich ,&nbsp;Katsunori Nakamura ,&nbsp;Koujirou Yamamoto ,&nbsp;Ayuko Imaoka ,&nbsp;Takeshi Akiyoshi ,&nbsp;Hisakazu Ohtani","doi":"10.1016/j.xphs.2024.10.037","DOIUrl":"10.1016/j.xphs.2024.10.037","url":null,"abstract":"<div><div>Some citrus fruits are known to cause clinically significant drug interactions by inhibiting intestinal cytochrome P450 (CYP) enzymes. This <em>in vitro</em> study aimed to investigate the kinetics of the inhibition of CYP3A4 and CYP2C19 by the juice of jabara, a Japanese citrus fruit that does not contain furanocoumarins such as 6′,7′-dihydroxybergamottin, and to identify the inhibitory compound(s).</div><div>CYP3A4 and CYP2C19 activity levels were determined <em>in vitro</em> using recombinant CYP preparations and their respective substrates. The ethyl acetate extract (EAE) of jabara juice was separated to isolate and identify the compound(s) that inhibited CYP3A4. Then, the time-dependent kinetics of the inhibition of CYP3A4 and CYP2C19 by the EAE and its inhibitory compound(s) were analyzed.</div><div>The EAE of jabara juice was found to inhibit CYP3A4 in a time-dependent manner. Two flavonoids, 3,3′,4′,5,6,7,8-heptamethoxyflavone (HpMF) and 3,3′,4′,5,6,7-hexamethoxyflavone (HxMF), were identified as the responsible compounds. HpMF and HxMF inhibited CYP3A4 activity in a concentration- and time-dependent manner, with inhibition constants (<em>K</em>_I) of 10.0 and 7.90 µM and maximal inactivation rate constants (<em>k</em>_inact,max) of 0.00856 and 0.0134 min⁻¹, respectively. The EAE did not inhibit CYP2C19, even when preincubation was employed. These findings imply that jabara juice may cause food-drug interactions via time-dependent inhibition of intestinal CYP3A4.</div></div>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":"114 2","pages":"Pages 849-856"},"PeriodicalIF":3.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142558085","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}

{"title":"Mechanistic characterization of iron-catalyzed oxidation of polysorbate 80: The role of ferrous iron, hydrogen peroxide, and superoxide","authors":"David S. Richards,&nbsp;Yaqi Wu,&nbsp;Christian Schöneich","doi":"10.1016/j.xphs.2024.10.053","DOIUrl":"10.1016/j.xphs.2024.10.053","url":null,"abstract":"<div><div>We investigated the role of individual radical species during Fe-catalyzed oxidation of PS80. Solutions containing 1 gL^-1 PS80 (0.1 % w/v) in 10 mM acetate buffer (pH 6) were exposed to various amounts of either Fe(II) or Fe(III), hydrogen peroxide (H₂O₂), and various enzymes or antioxidants. PS80 oxidation was measured using a fluorescence micelle assay (FMA) alongside LC-MS. Hydrogen peroxide inhibited PS80 oxidation in the presence of Fe(II) but promoted oxidation in the presence of Fe(III). Furthermore, Ferrostatin-1 (Fer-1), an antioxidant which is known to preferentially react with alkoxy radicals, inhibited PS80 oxidation in the presence of Fe(II). Superoxide dismutase (SOD) partially inhibited PS80 oxidation in the presence of either Fe(II) or Fe(III), suggesting that superoxide plays a role in both cases. Ferryl species (Fe^IV=O) or hydroxyl radicals (HO•), produced by the Fenton reaction, do not play a major role in the oxidation of PS80. Rather, oxidation was initiated by the reaction of both Fe(II) and Fe(III) with pre-existing lipid hydroperoxides on PS80, as well as via superoxide.</div></div>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":"114 2","pages":"Pages 923-933"},"PeriodicalIF":3.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142622887","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}

{"title":"Physical isolation strategy in multi-layer self-nanoemulsifying pellets: Improving dissolution and drug loading efficiency of ramipril","authors":"Ahmad Abdul-Wahhab Shahba ,&nbsp;Abdelrahman Y. Sherif ,&nbsp;Ehab M. Elzayat ,&nbsp;Shaukat Ali ,&nbsp;Mohsin Kazi","doi":"10.1016/j.xphs.2025.01.017","DOIUrl":"10.1016/j.xphs.2025.01.017","url":null,"abstract":"<div><div><em>Background and purpose:</em> Liquid self-nanoemulsifying drug delivery systems (SNEDDS) face challenges related to stability, handling, and storage. In particular, lipophilic and unstable drugs, such as ramipril (RMP) and thymoquinone (THQ), face challenges in oral administration due to poor aqueous solubility and chemical instability. This study aimed to develop and optimize multi-layer self-nanoemulsifying pellets (ML-SNEP) to enhance the stability and dissolution of ramipril (RMP) and thymoquinone (THQ). <em>Methods:</em> Liquid SNEDDS containing RMP and black seed oil (as a natural source of THQ) were prepared and characterized. The fluid-bed coating process was optimized by evaluating critical parameters such as inlet temperature, product temperature, air flow rate, atomizing air pressure, spray rate, and column height. Single-layer (SL-SNEP) and multi-layer (ML-SNEP) self-nanoemulsifying pellets were developed by applying various functional layers onto nonpareil sugar spheres. The pellets were characterized using scanning electron microscopy (SEM), differential scanning calorimetry (DSC), X-ray diffraction (XRD), and in vitro dissolution studies. <em>Results:</em> Optimized fluid-bed coating parameters resulted in high coating recovery (&gt;80%) and excellent mono-pellet percentages (≥97%). SEM analysis revealed well-defined, completely solidified layers in ML-SNEP. DSC and XRD studies suggested RMP amorphization. <em>In vitro</em> dissolution studies showed &gt;86% RMP and THQ release within 60 minutes for both SL-SNEP and ML-SNEP. The physical isolation strategy significantly improved drug loading efficiency, with ML-SNEP showing 109% RMP loading efficiency compared to 55% in SL-SNEP. The addition of moisture sealing and anti-adherent layers had no negative impact on drug release, with SNEP-5L (including the anti-adherent layer) showing higher dissolution efficiency for both RMP and THQ. <em>Conclusion:</em> This study successfully developed and optimized ML-SNEP as a novel approach for enhancing the stability and release of RMP and THQ. The physical isolation strategy was a key approach in enhancing drug loading efficiency while preserving the advantageous dissolution properties of liquid SNEDDS. This approach offers valuable insights for developing advanced oral drug delivery systems for poorly water-soluble and labile drugs.</div></div>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":"114 2","pages":"Pages 1326-1341"},"PeriodicalIF":3.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143066228","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}

{"title":"Application of one-class classification using deep learning technique improves the classification of subvisible particles","authors":"Takafumi Nakae ,&nbsp;Sunao Maruyama ,&nbsp;Toru Ogawa ,&nbsp;Susumu Hasegawa ,&nbsp;Masanori Obana ,&nbsp;Yasushi Fujio","doi":"10.1016/j.xphs.2024.11.023","DOIUrl":"10.1016/j.xphs.2024.11.023","url":null,"abstract":"<div><div>Capturing subvisible particles using flow imaging microscopy is useful for evaluating protein aggregates that may induce immunogenicity. Automated labeling is desirable to distinguish harmless components such as silicone oil (SO) from subvisible particles. The one-class classifier, which requires only target class data for model establishment, is suitable for machine learning and proposes a useful solution for distinguishing a subject with heterogeneous but stable distributions, such as SO. However, the effectiveness of the application of one-class classifiers to subvisible particles remains unclear. In this study, we investigated whether deep learning techniques can improve the performance on a variety of images. We prepared datasets using SO and two types of protein aggregates: immunoglobulin G-derived aggregates (Agg_IgG) and albumin-derived aggregates (Agg_Alb). The deep-learning technique improved the classification scores for both Agg_IgG and Agg_Alb. The classification scores for Agg_IgG were more satisfactory than those for Agg_Alb. Cluster analysis revealed that one-class classification using deep learning techniques achieved excellent effectiveness across almost all clusters in classifying Agg_IgG. Collectively, the deep learning technique remarkably improved the one-class classification of subvisible particles of Agg_IgG and Agg_Alb. Combined with deep learning, one-class classification can contribute to the evaluation of subvisible particles, particularly for Agg_IgG.</div></div>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":"114 2","pages":"Pages 1117-1124"},"PeriodicalIF":3.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142769895","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}

{"title":"Two recombinant cytomegalovirus antigens formulated with the SPA14 adjuvant system: Impact of temperature, pH and excipients on the stability of each antigen and adjuvant component","authors":"John M. Hickey ,&nbsp;Ozan S. Kumru ,&nbsp;François Dalençon ,&nbsp;Florence Arvis ,&nbsp;Charles Lutsch ,&nbsp;Sangeeta B. Joshi ,&nbsp;David B. Volkin","doi":"10.1016/j.xphs.2024.12.030","DOIUrl":"10.1016/j.xphs.2024.12.030","url":null,"abstract":"<div><div>By evaluating the stability profiles of each component of a vaccine candidate (antigens, adjuvants), formulation conditions to mitigate vaccine instability can be identified. In this work, two recombinant Cytomegalovirus (CMV) glycoprotein antigens (gB, Pentamer) were formulated with SPA14, a novel liposome-based adjuvant system containing a synthetic TLR4 agonist (E6020) and a saponin (QS21). Analytical characterization and accelerated stability studies were performed with the two CMV antigens, formulated with and without SPA14, under various conditions (temperature, pH, excipients). For the antigens, the Pentamer was less stable than gB, and the addition of SPA14 adjuvant had negligible impact. For the SPA14 components, minor pH shifts (caused by the buffer's temperature dependent pKa shifts) destabilized the liposome (particle size by DLS) and QS21, but E6020 was unaffected (integrity by RP-UHPLC and LC-MS, respectively). The addition of chelators and free radical scavengers stabilized both the QS21 and E6020 components, consistent with oxidative degradation catalyzed by trace metal-ions. Interestingly, QS21 and E6020 also displayed improved storage stability in the presence of the protein antigens. These results are discussed in terms of developing key stability-indicating assays to optimize formulation conditions to stabilize the two CMV antigens and the three components of the SPA14 adjuvant system.</div></div>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":"114 2","pages":"Pages 1224-1236"},"PeriodicalIF":3.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143047043","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}

{"title":"Drug product development and case studies for patient centric pediatric protein-based therapeutics","authors":"Annette Medina ,&nbsp;Mary N. Brown ,&nbsp;Emily Cox ,&nbsp;Sarah Donegan ,&nbsp;Sonia Dragulin-Otto ,&nbsp;Katiria Flores ,&nbsp;Nathalie Fuentes ,&nbsp;Lisa Glasser ,&nbsp;Stanley C. Kwok ,&nbsp;Ian Lent ,&nbsp;Angeliki Siapkara ,&nbsp;Yujing Wang","doi":"10.1016/j.xphs.2024.07.014","DOIUrl":"10.1016/j.xphs.2024.07.014","url":null,"abstract":"<div><div>The user of a pediatric drug includes not only the patient, but also their caregiver and healthcare provider, including nurses, doctors, and pharmacists. Therefore, adopting a patient-centric approach that focuses on all users is critical for the development of pediatric drug products. This article outlines the quality target product profile parameters and a patient-centric approach for the development of pediatric protein-based therapies. The use environment, formulation design, and preparation and in use stability considerations are described. An acceptability profile for the various routes of parenteral administration is described with a focus on pediatric age groups. Furthermore, a risk assessment approach is presented for the selection of excipients to be utilized in pediatric protein-based biopharmaceuticals. Several case studies are included which illustrate the selection of drug product parameters such as formulation, dose volume, and route of administration with the pediatric user in mind.</div></div>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":"114 2","pages":"Pages 681-689"},"PeriodicalIF":3.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142036114","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}

{"title":"In-situ formation and evaluation of N-nitrosamine drug substance related impurities in glycopeptides implying orbitrap mass spectrometry","authors":"Sree Teja Paritala,&nbsp;Nitish Sharma,&nbsp;Ravi P. Shah","doi":"10.1016/j.xphs.2024.10.056","DOIUrl":"10.1016/j.xphs.2024.10.056","url":null,"abstract":"<div><div>Nitrosamines, a class of N-nitroso compounds, have raised significant health concerns due to their established carcinogenicity. ICH M7 enlisted N-nitroso compounds in the so called cohorts of concern due to their carcinogenic effects. Glycopeptides (GPs) are complex molecules composed of peptide and glycan moieties. GPs serve as the last resort for the mitigation of bacterial infections, particularly against gram-positive bacteria. GPs are susceptible to nitrosamine drug substance related impurities (NDSRIs) contamination due to the presence of secondary amine in their core structure. The incidence of formation of NDSRI impurities in GPs could be either during their semi-synthetic route or storage. However, till date, no studies have been reported on the occurrence of NDSRI in GPs which is a pre-requisite. Hence, the current study investigates the plausible mechanisms and detection methods for the NDSRI in GPs. In-situ studies were performed to evaluate the possible formation of NDSRI in GPs. In the current study, GPs of different generations were screened for their potential of forming NDSRI impurities implying nitrosating agent. LC and LC<img>HRMS/MS studies were performed to identify the in-situ generated impurities. Interestingly, the formation of NDSRIs is evident in all the selected GPs. The molecular mechanisms and pathways for individual GPs and respective NDSRIs were elucidated. Interestingly, isomeric NDSRIs were also identified during in-situ generated samples. Using CPCA the potency scores and acceptable intakes for the NDSRIs were evaluated. Thus, this work aims to enhance the safety and efficacy of GPs ensuring compliance with the regulatory standards by advancing the understanding of NDSRIs in GPs.</div></div>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":"114 2","pages":"Pages 934-948"},"PeriodicalIF":3.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142755231","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}

{"title":"Qualification of mechanistic models in biopharmaceutical process development","authors":"Till Briskot,&nbsp;Dominik Hiltmann,&nbsp;Federico Rischawy,&nbsp;Joey Studts,&nbsp;Simon Kluters","doi":"10.1016/j.xphs.2024.11.021","DOIUrl":"10.1016/j.xphs.2024.11.021","url":null,"abstract":"<div><div>Mechanistic process models play an increasingly important role in biopharmaceutical process development and manufacturing in supporting process design, characterization, and informing process control strategies. Despite the potential of mechanistic models, there is currently no clear consensus or regulatory guideline on their qualification, i.e. the processes of determining whether a model is suitable to support decision making in process development. In this work, a systematic and risk-based qualification framework for mechanistic models in biopharmaceutical process development is introduced. The framework integrates key concepts from other modeling frameworks and guidelines such as the ASME V&amp;V 40 published by the American Society of Mechanical Engineers (ASME) and preliminary considerations in process models published by Quality Innovation Group (QIG) of the European Medicines Agency (EMA). Key concepts of the proposed framework are discussed using two case studies, including a model-informed optimization of a biopharmaceutical ultrafiltration and diafiltration process and a model-informed control strategy of a chromatography polishing step. The suggested framework can act as a foundation for dialogue and guide for other modelers in biopharmaceutical process development. It holds the capability to harmonize modeling procedures throughout the industry and establish an agreement on the qualification of mechanistic models in biopharmaceutical process development.</div></div>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":"114 2","pages":"Pages 1095-1107"},"PeriodicalIF":3.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142769939","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}