PDA Journal of Pharmaceutical Science and Technology最新文献

{"title":"Global health authorities review and approval trends for CMC post approval changes 2018-2024.","authors":"Karim Kacimi, Sunny Kamlesh Dave, Scott Roberts","doi":"10.5731/pdajpst.2025-000081.1","DOIUrl":"https://doi.org/10.5731/pdajpst.2025-000081.1","url":null,"abstract":"<p><p>The approval and implementation of Chemistry, Manufacturing, and Control (CMC) post-approval changes (PACs) by global health authorities are often lengthy and unpredictable in terms of requirements and timeline, potentially leading to drug shortages and hindering innovation in product quality and manufacturing processes. This study analyzes the review and approval times for CMC PACs from 2018 to 2024, focusing on alignment with the World Health Organization (WHO) recommendations for a maximum six-month review period for PACs. The analysis reveals a positive trend towards shorter approval times, with significant improvements observed post-2019. However, inconsistencies remain, particularly in the classification and procedural processes of CMC PACs across different countries. The study underscores the need for global harmonization of PAC frameworks and the adoption of WHO reliance principles to enhance the predictability of and efficiency of CMC lifecycle management. These improvements are crucial for strengthening the global supply chain, fostering innovation in pharmaceutical manufacturing, and ultimately ensuring timely patient access to essential medications.</p>","PeriodicalId":19986,"journal":{"name":"PDA Journal of Pharmaceutical Science and Technology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147777841","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Root Cause Determination for Customer Complaint Biopharmaceutical Drug Product Samples with Abnormal Appearance.","authors":"Yiwei Ma, Jian Liu, Alejandra Gallegos, Hans Lee, Dengfeng Liu, David Semin, Yasser Nashed-Samuel","doi":"10.5731/pdajpst.2025-000078.1","DOIUrl":"https://doi.org/10.5731/pdajpst.2025-000078.1","url":null,"abstract":"<p><p>Customer complaints due to drug product abnormalities may arise even with strict quality control measures at the manufacturing and healthcare provider levels, posing serious challenges for the manufacturers. In this paper, we report three compelling case studies which exemplify effectiveness of root cause analyses in addressing customer complaints of Amgen drug products. The three customer complaints from three different drug products reported the following issues: pink discoloration in one drug product vial, cloudy liquid with suspended particles in another drug product vial, and brown discoloration in the third drug product vial. Consequently, a comprehensive root cause analyses were performed to identify and rectify the underlying issue, thereby mitigating the recurrence of complaints. The root cause analysis of the three events ruled out manufacturing processes as the source of contamination. Instead, it was more likely that the contamination originated at the healthcare providers' facilities. Orthogonal analytical test methodologies were employed on the samples to identify any potential contaminants. The cloudy appearance, pink and brown discolorations in the three customers returned vials were caused by non-Amgen products. The first vial had cyanocobalamin injectable (vitamin B12), the second vial had fosaprepitant (a non-Amgen drug), and the third vial had iron and saline solution (likely injectable anemia drug). A possible explanation for the three complaint samples is that they were mishandled during the process of administering the drug products at the facilities of the healthcare providers. Following the identification of the likely sources of contamination, Amgen followed standard compliant-handling procedures, which may include communicating results back to complaints or health providers as appropriate. In conclusion, the pursuit of root cause determination is paramount in addressing customer complaints and ensuring the quality, safety, and efficacy of biopharmaceutical products.</p>","PeriodicalId":19986,"journal":{"name":"PDA Journal of Pharmaceutical Science and Technology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147778087","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparative Study of Matrix vs. Product-Specific Cleaning Validation Approaches.","authors":"Mahender Boyapally","doi":"10.5731/pdajpst.2026-000007.1","DOIUrl":"https://doi.org/10.5731/pdajpst.2026-000007.1","url":null,"abstract":"<p><p>Cleaning validation is an essential part of the present Good Manufacturing Practices (cGMP) of the pharmaceutical industry. This comparison paper discusses two main cleaning validation methods: the matrix (worst-case) approach and product-specific approach. The paper assesses the strengths, weaknesses, risk profiles and real-world application of both methodologies through the review of regulatory guidance, industry best practices, and case study findings. The matrix approach, which justifies cleaning according to worst-case scenarios of groups of related products, is highly resource-efficient though it calls for hard scientific justification. The product-specific method offers wholesome validation of every product transition but requires enormous resources. The present study is a framework of the choice of the proper validation strategy depending on the features of the facilities, the complexity of the products portfolio, and the results of the risk assessment. This analysis suggests that a combined strategy, comprising factors of both methodologies with visible residue limits (VRL) as a risk-based instrument, may provide an effective balance between regulatory compliance and operational performance.</p>","PeriodicalId":19986,"journal":{"name":"PDA Journal of Pharmaceutical Science and Technology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147717657","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Challenges for Visual Inspection and Particle Control in Cell Therapy Products.","authors":"Roman Mathaes, Antonio Burazer, Satish K Singh, John G Shabushnig, Atanas Koulov","doi":"10.5731/pdajpst.2025-000021.1","DOIUrl":"10.5731/pdajpst.2025-000021.1","url":null,"abstract":"<p><p>Cell therapy products represent a transformative class of advanced medicinal products with unique manufacturing and quality control challenges. Unlike conventional parenteral products, cell therapies consist of living cells-typically delivered as turbid, non-filterable suspensions-which inherently complicates the control and detection of visible particles (VPs) and subvisible particles (SvPs). This review outlines the distinctive risks associated with particle generation in autologous and allogeneic cell therapies and highlights limitations of existing pharmacopeial methods for particle testing. We identify three major sources of particles in cell therapy products: the manufacturing process with often several manual manipulation steps, the single-use manufacturing components, and the container closure systems. The complexity of the process is compounded by small batch sizes, short shelf life, and complex formulations, and thus traditional sampling and visual inspection approaches have limitations in their utility. Therefore, cell therapy products often require tailored inspection strategies and supplemental process simulations. We review the current global regulatory requirements (USP <790>, Ph. Eur. 2.9.20, JP 6.06), contrast US and EU definitions for particle types, and discusses practical gaps in harmonization. We further evaluate emerging technologies like flow imaging microscopy for SvP characterization and propose optimized visual inspection strategies tailored for turbid cell suspensions. However, preventative or preemptive control, rather than end-stage inspection, is recommended as the most effective strategy. This requires systematic risk assessment, raw material control, process simulations, and supplier collaboration. The authors advocate for the development of cell therapy-specific inspection standards and call for regulatory alignment to support consistent global development and patient access.</p>","PeriodicalId":19986,"journal":{"name":"PDA Journal of Pharmaceutical Science and Technology","volume":" ","pages":"255-263"},"PeriodicalIF":0.0,"publicationDate":"2026-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145308761","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrating Real-Time Viable Biofluorescent Particle Counters within Robotic Gloveless Isolators.","authors":"Noël Long, Manny Khera, Bobby Lumia","doi":"10.5731/pdajpst.2025-000032.1","DOIUrl":"10.5731/pdajpst.2025-000032.1","url":null,"abstract":"<p><p>Advanced technologies in both aseptic filling and environmental monitoring are coming together to improve the resilience and sterility assurance of aseptic processing. Continuous, real-time environmental monitoring using biofluorescent particle counters (BFPCs) to detect viable and nonviable particles during the aseptic filling process for injectable drugs is gaining traction as an accepted alternative to conventional methods such as active air sampling instruments. Evolving regulatory guidance, including EU Annex 1 guidelines, are increasingly recommending the adoption of isolator technology as well as continuous environmental monitoring during GMP processes, including technologies that offer real-time feedback during drug product manufacturing. Computational flow dynamics and airflow visualization studies are additional tools that support the design of equipment and determination of locations for environmental monitoring. The current nutrient culture media growth-based environmental monitoring, rooted in science from 150 years ago, is unable to keep pace with recent technological advances and the ability to immediately react to an out-of-control state. Here we examine the design of an isolator that eliminates human intervention and indirect product contact parts during aseptic fill finish operations and present computational fluid dynamics (CFD) studies verified by airflow visualization, along with the incorporation of BFPCs at critical areas. Also, we report the results of the interference study characterizing the baseline results for detection of total particles (nonviable plus viable) using a BFPC within a robotic gloveless isolator during dynamic and static operating conditions. The results of our study using BFPCs demonstrate that airflow in the robotic gloveless isolator provides protection of critical areas from contamination during the tub peeling process, and that the stoppering process in this environment does not generate detectable particles. During dynamic conditions and material transfer, the study demonstrates the design of the robotic gloveless isolator prevents false positives from interfering with materials during normal operations.</p>","PeriodicalId":19986,"journal":{"name":"PDA Journal of Pharmaceutical Science and Technology","volume":" ","pages":"264-278"},"PeriodicalIF":0.0,"publicationDate":"2026-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145998752","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"LC-MS/MS-Based Determination of Gadobutrol Residues for Pharmaceutical Cleaning Validation.","authors":"Gözde Gülin İnan, İbrahim Daniş, Neşet Neşetoğlu, Durisehvar Özer Ünal","doi":"10.5731/pdajpst.2025-000086.1","DOIUrl":"10.5731/pdajpst.2025-000086.1","url":null,"abstract":"<p><p>The hazards of gadolinium, widely used in magnetic resonance imaging to detect pathological lesions, should not be overlooked. Due to its pharmacological effects, any contamination from gadobutrol production poses serious health risks. Therefore, it is imperative that gadobutrol residues continue to be completely removed from production equipment. This study aimed to develop and validate a highly sensitive liquid chromatography with tandem mass spectrometry (LC-MS/MS) method for the quantitative detection of gadobutrol residues on stainless-steel surfaces and to apply it in a cleaning validation study in accordance with regulatory guidelines. Swab samples were collected from production equipment surfaces after cleaning procedures. Method validation parameters such as specificity, linearity, precision, accuracy, limit of detection (LOD), and limit of quantitation (LOQ) were evaluated. Recovery studies were performed using spiked stainless-steel plates to determine recovery rates. Swab recovery data were incorporated into the analysis of actual equipment samples. The LC-MS/MS method showed excellent linearity (r² ≥ 0.9999) within the range of 5-500 ng/mL. LOD and LOQ values were 2 ng/mL and 5 ng/mL, respectively. Intraday and interday accuracy and precision were within acceptable limits. Gadobutrol was found to be stable under short-term storage and autosampler conditions. The recovery rate was calculated as 83%. A sensitive, selective, and robust analytical method was successfully developed and validated for gadobutrol. This study is the first to perform cleaning validation for gadobutrol using LC-MS/MS with such sensitivity. The findings contribute significantly to both cleaning validation and analytical method development literature in the pharmaceutical industry.</p>","PeriodicalId":19986,"journal":{"name":"PDA Journal of Pharmaceutical Science and Technology","volume":" ","pages":"229-238"},"PeriodicalIF":0.0,"publicationDate":"2026-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146207309","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The High Risk of Mold Contamination in Biopharmaceutical Facilities: Gypsum Wall Materials versus uPVC Wall Panels-Regulatory Scrutiny, Recalls and Facility Shutdowns.","authors":"Maik Jornitz","doi":"10.5731/pdajpst.2025-000082.1","DOIUrl":"10.5731/pdajpst.2025-000082.1","url":null,"abstract":"<p><p>Mold contamination in biopharmaceutical manufacturing is a serious patient safety, product quality, and regulatory risk. This paper reviews the mechanisms by which wall construction materials contribute to microbial ingress and colonization, compares traditional gypsum (drywall) construction with nonporous wall panel systems such as unplasticized polyvinyl chloride (uPVC)/modular panels, and documents regulatory actions, recalls, and plant shutdowns linked to fungal contamination. Drawing on industry guidance, inspection findings, and published case histories, it explains why gypsum-based \"stick-built\" walls pose higher long-term mold risk in many life-science environments and presents engineering, procedural, and design strategies to reduce risk (material selection, environmental control, inspection/monitoring, construction sequencing, and remediation policy). Practical recommendations are offered for facility owners, designers, and quality/regulatory teams who must justify capital choices and satisfy regulators.</p>","PeriodicalId":19986,"journal":{"name":"PDA Journal of Pharmaceutical Science and Technology","volume":" ","pages":"279-286"},"PeriodicalIF":0.0,"publicationDate":"2026-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146207302","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The European Qualified Person: Legal Accountability, Quality Leadership, and AI Integration in Modern Pharmaceutical Manufacturing: Navigating Complex Therapies and AI-Supported Oversight to Safeguard Patient Safety.","authors":"Mario Stassen","doi":"10.5731/pdajpst.2025-000067.1","DOIUrl":"10.5731/pdajpst.2025-000067.1","url":null,"abstract":"<p><p>The European Qualified Person (QP) holds unique legal responsibility for certifying batch release, ensuring patient safety, and maintaining regulatory compliance. Modern pharmaceutical manufacturing-especially in biologics, advanced therapy medicinal products (ATMPs), and personalized medicines-generates complex, multi-site, data-rich environments that challenge traditional oversight. Artificial Intelligence (AI) offers predictive analytics, anomaly detection, and trend recognition to support decision-making but cannot currently replace the QP's scientific judgment or legal accountability. The forthcoming Annex 22 introduces Human-in-the-Loop (HITL) frameworks that embed human oversight within AI-supported processes, aligning technological advancement with regulatory control. This review explores evolving QP responsibilities, core and emerging competencies, AI integration within Quality Risk Management (QRM) and Good Manufacturing Practice (GMP) frameworks, and ethical considerations, illustrated with practical case studies. By developing AI literacy and applying HITL oversight, QPs can more effectively translate technological potential into transparent, science-based, and patient-centered batch-release decisions.</p>","PeriodicalId":19986,"journal":{"name":"PDA Journal of Pharmaceutical Science and Technology","volume":" ","pages":"239-247"},"PeriodicalIF":0.0,"publicationDate":"2026-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145768779","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Design Differences and Usability Risks in GLP-1 Pen Injectors: A Comparative Study of a Generic and Reference Device.","authors":"Laurie Brunet-Manquat, Anne Combedazou, Claire Ramus, Cécile Frolet","doi":"10.5731/pdajpst.2025-000043.1","DOIUrl":"10.5731/pdajpst.2025-000043.1","url":null,"abstract":"<p><strong>Objective: </strong>To provide preliminary insights into whether a proposed generic combination product injector for glucagon-like peptide-1 (GLP-1) receptor agonist administration can be substituted for the delivery device constituent part of the Reference Listed Drug (RLD) without the need for additional training or health care provider intervention for Abbreviated New Drug Application (ANDA) submissions. A preliminary comparative use Human Factors study was conducted with 14 participants experienced with the RLD, including patients and caregivers. Participants simulated critical tasks using a delivery device constituent part of both the proposed generic combination product and the RLD. Observational data, use error rates, and subjective feedback on acceptability and ease of use were collected and analyzed. The overall use error rate was slightly higher for the proposed generic combination product (79%) compared to that of the RLD pen (71%), corresponding to one additional participant experiencing failure. Most use errors were not attributed to differences in external critical design attributes but rather to user habits or procedural misunderstandings. Notably, 93% of participants demonstrated similar usability profiles across both devices. Design differences, such as the outward translation of the dose set knob and increased injection force of the proposed generic combination product, were associated with a small number of use errors, but these were resolved after a single use, indicating a rapid learning effect. Acceptability and ease-of-use ratings were high for both devices, with 87% of participants expressing comfort in switching between them. Despite \"other design differences\", the proposed generic combination product injector demonstrated comparable usability to the RLD pen without additional risks. Most observed use errors were not device-specific and were resolved quickly, suggesting limited clinical impact in real-world use. These findings support the potential substitutability of the proposed GLP-1 generic combination product for the RLD and contribute to de-risking the final comparative use Human Factors evaluations required for ANDA.</p>","PeriodicalId":19986,"journal":{"name":"PDA Journal of Pharmaceutical Science and Technology","volume":" ","pages":"218-228"},"PeriodicalIF":0.0,"publicationDate":"2026-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146207285","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PDA Week 2026.","authors":"","doi":"10.5731/pdajpst.2026.02612","DOIUrl":"https://doi.org/10.5731/pdajpst.2026.02612","url":null,"abstract":"","PeriodicalId":19986,"journal":{"name":"PDA Journal of Pharmaceutical Science and Technology","volume":"80 2","pages":"217"},"PeriodicalIF":0.0,"publicationDate":"2026-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147654798","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}