PDA Journal of Pharmaceutical Science and Technology最新文献

{"title":"Establishment of Limit of In Vitro Cell Age (LIVCA) for Biologics Manufacturing Process.","authors":"Barbara Tevelev, Sharyn Farnsworth, Sarah Kaminsky-Pontell, Urška Verbovšek, Guanghua Benson Li","doi":"10.5731/pdajpst.2025-000013.1","DOIUrl":"https://doi.org/10.5731/pdajpst.2025-000013.1","url":null,"abstract":"<p><p>This white paper explores current practices and industry experiences for establishing the Limit of In Vitro Cell Age (LIVCA) in biologics manufacturing. As per the International Council for Harmonization of Technical Requirements of Pharmaceuticals for Human Use (ICH), characterization and testing of banked cell substrate is a critical component of the control of biotechnological and biological products. Regulatory agencies require the establishment of LIVCA for the use of master cell bank (MCB) and working cell banks (WCBs) in commercial manufacturing of biologics to demonstrate that the maximum in vitro cell age of cells used in the production process has no impact on product quality and process consistency over the duration of cell culture expansion and manufacturing process. This white paper reviews the methodologies for genotypic, phenotypic, and product quality characterization for LIVCA while highlighting the necessity of aligning industry practices with regulatory expectations to expedite market approval. It discusses the strategies for implementing LIVCA, regulatory guidelines, expectations that shape different industry practices, and provides an overview of approval experiences including those based on data derived from production cells expanded under pilot plant scale or using representative scale-down models. Through a collaborative approach involving industry leaders based on an industry-wide survey coordinated by the BioPhorum Operations Group (BPOG), we aim to streamline and accelerate LIVCA timelines, while ensuring robust manufacturing processes and adherence to high compliance standards as companies design and implement their LIVCA strategies efficiently and effectively to support commercialization applications.</p>","PeriodicalId":19986,"journal":{"name":"PDA Journal of Pharmaceutical Science and Technology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145081212","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":"A Guide to Navigating Quality Control Requirements for Alternative and Rapid Microbial Methods in Sterility and Mycoplasma Testing Across the Asia Pacific Region.","authors":"Juliana Gutierrez","doi":"10.5731/pdajpst.2024-003031.1","DOIUrl":"https://doi.org/10.5731/pdajpst.2024-003031.1","url":null,"abstract":"<p><p>While alternative and rapid microbiological methods (ARMM) have gained broader acceptance in Europe and the United States, where guidance on their validation and implementation has been made available by the European Pharmacopoeia and United States Pharmacopoeia and their use has been supported by both regulators and industry groups, their adoption in other regions such as Asia Pacific has been more limited. This article aims to review the regulatory landscape for ARMM in the Asia Pacific region, focusing specifically on sterility and mycoplasma testing. It will examine relevant pharmacopoeial chapters and local guidelines in key pharmaceutical markets, including China, Taiwan, Japan, South Korea, India, Indonesia, Thailand, and Vietnam. The analysis will be limited to markets with their own pharmacopoeia, providing a comprehensive guide to navigating the landscape of existing and future regulations while assessing the readiness of these markets to adopt these new technologies.</p>","PeriodicalId":19986,"journal":{"name":"PDA Journal of Pharmaceutical Science and Technology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145081251","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":"Considerations for the Validation of Non-CFU Based Bio-Fluorescent Particle Counting Technologies.","authors":"Cynthia Martindale, Caroline Dreyer, Cedric Joossen, Joanny Salvas, Kim Perkins, Mike Dingle, Petra Merker, Philip Villari, Tony Cundell, Margit Franz-Riethdorf, Patrick Hutchins","doi":"10.5731/pdajpst.2024-003036.1","DOIUrl":"https://doi.org/10.5731/pdajpst.2024-003036.1","url":null,"abstract":"<p><p>The use of Bio-Fluorescent Particle Counting technologies as a rapid, alternative method to monitor microbial contamination in water and cleanroom air samples has been of interest to the pharmaceutical industry for several years. These technologies are a non-growth-based method that use the detection of particle scatter and intrinsic fluorescence to categorize detected particles as biologic or non-biologic. As a result, the systems report in a unit of measure not equivalent to the colony forming unit. Although guidance on the validation of alternative microbial methods is available, significant challenges can exist when validating non-growth based alternative methods compared to the growth-based compendial method. Collaborators in the Modern Microbial Methods (M³) industry working group provide thoughts and recommendations on a method validation pathway for the non-growth-based bio-fluorescent particle counting technology. Technology specific recommendations on the primary and secondary validation are provided with considerations on the applicability of individual validation parameters and associated acceptance criteria for this emerging technology that does not rely on the colony-forming unit.</p>","PeriodicalId":19986,"journal":{"name":"PDA Journal of Pharmaceutical Science and Technology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144964804","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":"Use of the Retention Index to Secure Correct Identities in GC/MS.","authors":"Piet Christiaens, Dennis Jenke, Jan Baeten, Philippe Verlinde, Jean-Marie Beusen","doi":"10.5731/pdajpst.2025-000008.1","DOIUrl":"https://doi.org/10.5731/pdajpst.2025-000008.1","url":null,"abstract":"<p><p>Drug products and medical device extracts are chromatographically analysed via non-targeted analysis to detect, identify, and quantify organic leachables; GC/MS addresses primarily volatile and semi-volatile organic leachables. Identities of compounds detected by GC/MS are often secured by mass spectral matching (MSM), where the mass spectrum is compared to reference spectra from a spectral library. Compounds whose reference spectrum closely matches the analytical spectrum are candidate identities for the compound of interest. Even when rigorously applied, MSM can lead to incorrect candidate identities. Avoiding misidentifications is important as reporting misidentified compounds can severely impact toxicological risk assessment, potentially leading to false conclusions about patient safety. The retention index (RI) is an effective means of evaluating an identity secured by MSM. The agreement between an experimental RI and a reference RI likely corroborates or refutes an MSM identity, although in certain cases the RI comparison may be inconclusive. The use of RI matching to corroborate MSM-based identities was investigated. Experimental and calculated RI values from the NIST23 library were compared to experimental RI values. Both classes of NIST23 RI values correlated well with the experimental RI obtained for 3140 compounds with confirmed identities, leading to the development of a strategy where reference RI-information from NIST23 can be used to support, accept, or reject candidate MSM structures. Using a confusion matrix, it is concluded that within the boundaries set for mass spectral matching (MSM>85; top 5 ranked candidates), an absolute difference in RI between the experimental value and the NIST reference value (|ΔRI|) of equal or lower than 20 showed a high identification precision and corroborates proposed identified. A |ΔRI| value higher than 50 showed a very low precision, which consequently rejects these identifications. |ΔRI| values between 20 and 50 are indiscriminate, meaning that while the identity proposed via MSM is accepted, it is considered to be tentative and uncorroborated.</p>","PeriodicalId":19986,"journal":{"name":"PDA Journal of Pharmaceutical Science and Technology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144964780","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":"Digital Reference Materials: A New Standard for Quality and Compliance in Bio/Pharmaceutical Manufacturing.","authors":"Vadim Klyushnichenko","doi":"10.5731/pdajpst.2025-000039.1","DOIUrl":"https://doi.org/10.5731/pdajpst.2025-000039.1","url":null,"abstract":"<p><p>As biopharmaceutical manufacturing evolves toward digitalization, the need for structured, interoperable, and regulatory-compliant data is intensifying. Digital Reference Materials (dRMs), the machine-readable counterparts of physical reference standards, have emerged as critical tools for enhancing data integrity, enabling automated quality control (QC), and supporting regulatory transparency. This article explores the definition, structure, and implementation of dRMs within the pharmaceutical landscape. It examines regulatory initiatives such as the FDAâs eCTD 4.0 and KASA, pharmacopeial digitization efforts, and pioneering commercial applications like Merck/MilliporeSigma's ChemisTwin™. Technical foundations, such as XML, JSON, and AnIML formats, are discussed alongside their integration into laboratory systems such as LIMS, ELNs, and CDS platforms. Special attention is given to the challenges of implementing dRMs in chromatography, where method-specific variability complicates standardization. Ultimately, dRMs are positioned as enablers of intelligent manufacturing, supporting AI-driven analytics, digital twins, and harmonized global quality systems. This work underscores the strategic imperative for stakeholders to invest in digital infrastructure, standards, and collaboration to fully realize the potential of digital reference materials in modern pharmaceutical development.</p>","PeriodicalId":19986,"journal":{"name":"PDA Journal of Pharmaceutical Science and Technology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144964835","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":"NIIMBL-facilitated active listening meeting between industry and FDA identifies common challenges for adoption of alternative and rapid microbiological methods.","authors":"Jennifer L Mantle, Eugene Schaefer, Kelvin H Lee","doi":"10.5731/pdajpst.2025-000026.1","DOIUrl":"https://doi.org/10.5731/pdajpst.2025-000026.1","url":null,"abstract":"<p><p>Alternative and rapid microbiological methods (ARMM) used in biopharmaceutical manufacturing have potential advantages over current compendial methods in that they can enable faster product release and improved process monitoring and quality assurance. There is value in community-wide discussion on ARMMs to help understand the challenges of ARMM adoption in biopharmaceutical manufacturing. The National Institute for Innovation in Manufacturing Biopharmaceuticals (NIIMBL) attempted to understand the successes and challenges around ARMM adoption through surveys, interviews, and a facilitated Active Listening Meeting between industry and FDA representatives. Through these interactions, it was observed that many organizations have successfully implemented ARMMs in approved manufacturing processes, suggesting an absence of significant regulatory obstacles to implementation. Further, five key elements impacting technology adoption were identified: technology readiness, vendor support, organizational adoption readiness, business case/economics, and regulatory interaction. The Active Listening Meeting format proved valuable for fostering honest and informal conversations between both sponsors and regulators.</p>","PeriodicalId":19986,"journal":{"name":"PDA Journal of Pharmaceutical Science and Technology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144964845","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":"Charting the Universe of Organic Extractables and Leachables Compounds with Confirmed identities.","authors":"Dennis Jenke, Piet Christiaens, Adam Jenke, Jan Baeten, Philippe Verlinde, Jean-Marie Beusen","doi":"10.5731/pdajpst.2025-000007.1","DOIUrl":"https://doi.org/10.5731/pdajpst.2025-000007.1","url":null,"abstract":"<p><p>Drug product leachables are substances that are leached from the drug products manufacturing system components during manufacturing operations, drug product packaging systems during storage over shelf-life, and delivery systems during administration. Medical device leachables are substances that are released from medical devices during their clinical use. Thus, packaged drug products and medical devices are profiled for leachables (and/or extractables as probable leachables) to establish that the levels of leachables are sufficiently small that they present a negligible risk of adversely affecting patient health. This profiling is accomplished by screening the drug product or extracts of the medical device for released organic substances via nontargeted analysis (NTA) employing chromatographic methods coupled with mass spectrometric detection.The topics of how many possible organic extractables and leachables (E&L) there are and what are the most commonly reported organic E&Ls has been widely discussed in the E&L community of practice.One means of charting this universe of organic extractables and leachables is to review and collate those substances that have been encountered over the course of performing E&L studies. To this end, Nelson Labs Europe, a major contract research organization performing E&L testing for decades, has collated the results of several thousand E&L studies performed over the past several years, representing modern best practices in E&L assessment. These collated results, considering only those compounds reported with confirmed identities, are summarized and discussed herein. Although the use of compounds with only confirmed identities limits the number of considered compounds somewhat, so doing ensures that potentially false identifications and not published and do not result in a biased analysis of the collected information.</p>","PeriodicalId":19986,"journal":{"name":"PDA Journal of Pharmaceutical Science and Technology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144964750","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":"Comparison of Small Virus Clearance and Flowrates Between Meissner's SepraPor^® Hollow Fiber Ultrafiltration 50 kDa and 500 kDa Filter Membranes Using ΦX174 Bacteriophage: Poster Presented at PDA Week 2025.","authors":"Zachary Bendiks, Mao Kohara, Leesa McBurnie","doi":"10.5731/pdajpst.2025.25406","DOIUrl":"https://doi.org/10.5731/pdajpst.2025.25406","url":null,"abstract":"<p><p>Viral clearance by virus-retentive filters is a crucial step in many biomanufacturing process streams, including production of monoclonal antibodies and cell culture media. Studies with model viruses or bacteriophage are needed to determine whether a specific filter should be categorized as a small or large virus retentive filter. In this study, viral retention and flowrates were compared between Meissner's 50 kDa and 500 kDa SepraPor® Hollow Fiber (HF) Ultrafiltration (UF) membranes used for Tangential Flow Filtration (TFF). These filters were challenged with ∼10 million plaque forming units (PFU) of the small bacteriophage ΦX174 suspended in deionized (DI) water. It was determined that the 50 kDa SepraPor® HF UF membranes gave log-reduction values (LRVs) ≥ 5 with flowrates ranging from 15.9 to 46.7 mL/min at 15 psi constant pressure. The 500 kDa SepraPor® HF UF membranes gave LRVs ≤ 0.74 with flowrates ranging from 8.8 to 286 mL/min. These results show that Meissner's 500 kDa SepraPor® filter membrane does not retain ΦX174 in water and does not function as a small virus retentive filter, while the 50 kDa SepraPor® filter membrane gives robust clearance of ΦX174 and can be categorized as a small virus retentive filter.</p>","PeriodicalId":19986,"journal":{"name":"PDA Journal of Pharmaceutical Science and Technology","volume":"79 4","pages":"434-435"},"PeriodicalIF":0.0,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144765172","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":"Lean Science - Funding for Science or Not?","authors":"","doi":"10.5731/pdajpst.2025.001944","DOIUrl":"https://doi.org/10.5731/pdajpst.2025.001944","url":null,"abstract":"","PeriodicalId":19986,"journal":{"name":"PDA Journal of Pharmaceutical Science and Technology","volume":"79 4","pages":"355-356"},"PeriodicalIF":0.0,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144765184","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":"Regulatory Data Insights and Methods of Extraction and Analysis: Poster Presented at PDA Week 2025.","authors":"George Kwiecinski, Zephaniah Odidika","doi":"10.5731/pdajpst.2025.25410","DOIUrl":"10.5731/pdajpst.2025.25410","url":null,"abstract":"<p><p>This study investigates trends in FDA warning letter issuance between 2019 and 2023, focusing on the agency's efficiency and evolving priorities during this period. By analyzing both quantitative and qualitative data, the research highlights an increase of 43% in warning letters issued per 100 inspections. Using a novel approach combining regex filtering and web scraping, this presentation examines recurring keywords, department-specific citations, and legal references. The analysis aims to help attendees understand how structured data from regulatory agencies can be harnessed to improve compliance and inspection readiness.</p>","PeriodicalId":19986,"journal":{"name":"PDA Journal of Pharmaceutical Science and Technology","volume":"79 4","pages":"442-443"},"PeriodicalIF":0.0,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144765191","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}