PDA Journal of Pharmaceutical Science and Technology最新文献

{"title":"Defining a Generic Technology Transfer Process for Use Across the Biopharmaceutical Manufacturing Industry.","authors":"Jonathan Moore, Diana Chinchilla-Olszar, Mary Switzer, David Nellis, Dan Lasko, Ruth de la Fuente Sanz, Carrington Edmunds, Gene Schaefer, Alex Gadberry, Jennifer Nicole Earley, Mithun N Thimothy, Kelvin H Lee","doi":"10.5731/pdajpst.2024-003037.1","DOIUrl":"10.5731/pdajpst.2024-003037.1","url":null,"abstract":"<p><p>The technology transfer process varies widely between organizations across the biopharmaceutical industry. This variation amplifies the complexity of transfers and negatively impacts the communication of critical information. Organizations tend to either have their own established inflexible processes or unclearly defined processes that change over time. This lack of standardization is compounded as individual companies redefine their processes to meet changing requirements. This creates inefficiencies and barriers to collaboration between organizations due to dissimilar technology transfer processes. Additionally, the industry is evolving rapidly with companies adopting new and novel processes (e.g<i>.,</i> continuous processing, new modalities) to meet the global demand for biopharmaceuticals. As the processes become more complex and divergent, the need for a generic technology transfer process increases. This National Institute for Innovation in Manufacturing Biopharmaceuticals (NIIMBL) authored paper defines a generic technology transfer process using input from a broad range of subject matter experts from across the industry. This generic definition, which is not specific to any one company or any specific implementation, is provided as a starting point for organizations to build on in the future.</p>","PeriodicalId":19986,"journal":{"name":"PDA Journal of Pharmaceutical Science and Technology","volume":" ","pages":"619-637"},"PeriodicalIF":0.0,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144643105","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":"RACS: An Integrated FMEA-HACCP Framework for Advanced Risk Assessment and Control in Regulated Industries.","authors":"Prachi Sawant Raschdorf, R van der Galiën","doi":"10.5731/pdajpst.2026-000014.1","DOIUrl":"https://doi.org/10.5731/pdajpst.2026-000014.1","url":null,"abstract":"<p><p>Risk assessment is a fundamental requirement for ensuring compliance with Good Manufacturing Practice (GMP) across pharmaceutical manufacturing and other regulated industries. Established methodologies such as Failure Modes and Effects Analysis (FMEA) and Hazard Analysis and Critical Control Points (HACCP) are widely used; however, each presents inherent limitations when applied independently. FMEA provides a quantitative framework for prioritizing risks, while HACCP offers a structured qualitative approach for hazard identification and control.This article proposes an integrated methodology, termed Risk Assessment & Control Strategy (RACS), which combines the strengths of both FMEA and HACCP to deliver a more comprehensive and robust framework for risk management. The RACS approach enhances the evaluation of hazards, supports the definition and implementation of effective control measures, and facilitates continuous improvement. In addition to serving as a structured risk assessment tool, RACS can also be applied as a practical framework for developing and supporting key risk management documents.In the context of recent regulatory developments, particularly the revised EudraLex Volume 4 Annex 1 guidelines effective from 25 August 2023, there is increased emphasis on contamination control and lifecycle-based risk management. Manufacturers are required to demonstrate that contamination risks are systematically identified, assessed, and effectively controlled throughout the manufacturing process. A robust Contamination Control Strategy (CCS), supported by Quality Management System (QMS) data and expert input, must therefore be grounded in sound risk assessment principles.The application of RACS to key quality risk management documents, including Sterility Assurance Risk Assessment (SARA) and CCS, is explored in this article. The methodology can be applied both to the development of CCS as an integrated, risk-based document and to the preparation of individual risk assessments that support a holistic CCS framework. Furthermore, integrating SARA within CCS using the RACS framework reduces duplication, optimizes resource utilization, and strengthens overall risk governance and traceability.Although particularly relevant to pharmaceutical manufacturing, the RACS methodology is adaptable to a wide range of regulated sectors, including food production, medical devices, biotechnology, cosmetics, and chemical manufacturing. Its structured, hybrid approach provides organizations with a versatile tool to systematically evaluate hazards, quantify risks, and implement effective, science-based control strategies.</p>","PeriodicalId":19986,"journal":{"name":"PDA Journal of Pharmaceutical Science and Technology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149063331","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":"Setting a Fill Weight Target and Control Limits for Drug Product Presentations.","authors":"Cindy D Ren, R Matthew Fesinmeyer, Nitin Rathore","doi":"10.5731/pdajpst.2026-000037.1","DOIUrl":"https://doi.org/10.5731/pdajpst.2026-000037.1","url":null,"abstract":"<p><p>For a given drug product presentation, the design of the fill weight strategy is a critical element to ensure that patients receive the correct dose. The fill weight strategy is comprised of fill weight target selection and the action limits around the target. Health regulatory agencies and pharmacopoeia are the primary sources of guidance on setting the fill weight strategy. The focus of this publication is to share practical approaches to the design of liquid and lyophilized drug product presentations, based on knowledge of regulatory guidance, drug product formulation properties, manufacturing capabilities, and knowledge of the primary container and in-use components. This is illustrated through four hypothetical case studies that are based on real-world experience. Considerations that need to be taken into account for liquid vs lyophilized, volume-based versus container-based dosing, and biosimilar presentations are discussed. The application and advantages of real-time release testing for deliverable volume of liquid drug products and total protein content of lyophilized drug products are also described. Furthermore, in order to more effectively discuss this topic across the industry and with health agencies, a standardized nomenclature for common terms related to fill weight strategy is proposed.</p>","PeriodicalId":19986,"journal":{"name":"PDA Journal of Pharmaceutical Science and Technology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148955935","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":"Key Contamination Control Trends Identified in Recent FDA Warning Letters.","authors":"Irina Pototskaia","doi":"10.5731/pdajpst.2026-000063.1","DOIUrl":"https://doi.org/10.5731/pdajpst.2026-000063.1","url":null,"abstract":"<p><p>Contamination control failures cited in recent U.S. Food and Drug Administration (FDA) warning letters increasingly reflect systemic quality management gaps rather than isolated technical errors. This review analyzes ten FDA warning letters issued between February and May 2026 to sterile drug manufacturers, outsourcing facilities, radiopharmaceutical facilities, manufacturers of terminally sterilized products, and selected non-sterile drug manufacturers, examining recurring deficiencies in environmental monitoring, aseptic processing, personnel qualification, sterility assurance, cleaning and disinfection, and Contamination Control Strategy (CCS) integration. Individual observations were grouped into six recurring trend categories using a trend matrix approach, with investigation and CAPA effectiveness (cited in 8 of 10 letters) emerging as the most frequent deficiency, followed by aseptic processing, environmental monitoring, and sterility assurance (7 of 10 each). The analysis demonstrates that FDA's enforcement posture increasingly emphasizes operational effectiveness over the mere existence of written procedures, an approach closely aligned with the lifecycle-based CCS framework introduced in the 2022 revision of EU GMP Annex 1. A structural mapping between Annex 1 elements and the identified FDA trends reveals substantial convergence between U.S. and European regulatory expectations, suggesting that alignment with Annex 1 principles may help reduce the risk of similar FDA observations. Based on these findings, three priority actions are proposed for manufacturers: an annual CCS effectiveness review, a dedicated environmental monitoring trend review board, and quantitative CAPA effectiveness metrics. This trend analysis is intended to support practitioners in microbiology, quality assurance, and regulatory compliance in evaluating whether their contamination control systems function as an integrated, preventive lifecycle discipline rather than a collection of disconnected procedural controls.</p>","PeriodicalId":19986,"journal":{"name":"PDA Journal of Pharmaceutical Science and Technology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148955781","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":"Quantitative Aspects of Non-targeted Analysis for Organic Extractables/Leachables; Insights Secured by Considering the FDA CLAP List Compounds.","authors":"Dennis Jenke, Piet Christiaens, Jan Baeten, Philippe Verlinde","doi":"10.5731/pdajpst.2026-000062.1","DOIUrl":"https://doi.org/10.5731/pdajpst.2026-000062.1","url":null,"abstract":"<p><p>Substances released from a drug product's manufacturing, packaging, and delivery system are termed leachables. Medical device leachables are released during their clinical use. Packaged drug products and medical devices are profiled for leachables (and/or extractables as probable leachables) by screening the drug product or extracts via non-targeted analysis (NTA) employing chromatography coupled with mass spectrometric detection.A leachable's concentration is important as concentration is establishes a patient's exposure to leachables during the clinical use of a drug product or medical device.Two issues are relevant when quantifying extractables or leachables (E/L) during NTA: when is quantitation necessary, and how is quantitation accomplished? Quantitation for toxicological safety risk assessment is necessary if the E/L is present at a level that exceeds the Analytical Evaluation Threshold (AET). To address compound-to-compound variation in analytical response, the AET is lowered via an Uncertainty Factor (UF).Estimated concentrations for identified E/Ls are accurate if either a reference standard is available for the E/L or the E/L can be linked to a surrogate reference compound. However, these approaches are not applicable to unidentified E/Ls or when reference compounds are unavailable.The means for calculating the UF and the use of a universal quantitation surrogate, specifically the median relative response factor (RRF) of a data set of compounds, to estimate the concentration of unidentified E/L are considered herein. Using the FDA CLAP list as a reference, this manuscript concludes that the proper calculation of the UF involves the median RRF and the RRF at the 16% percentile. Furthermore, this manuscript establishes that methods coupling liquid chromatography with mass spectrometric detection (electrospray ionization, ESI) are inaccurate when quantifying unidentified E/Ls given the large variation in RRF values. However, as RRF values for GC/MS are less variable, concentrations estimated for unidentified E/Ls using RRF_median can be accurate and protective.</p>","PeriodicalId":19986,"journal":{"name":"PDA Journal of Pharmaceutical Science and Technology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148955975","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":"Water Activity as a Primary Indicator of Moisture in Lyophilized Products: Linking Non-Destructive Headspace Analysis to Total Moisture via Moisture Sorption Isotherms.","authors":"Allison Alix Caudill, Ken Victor, Haydee Lanuza, Sharon Chen, James Veale","doi":"10.5731/pdajpst.2026-000044.1","DOIUrl":"https://doi.org/10.5731/pdajpst.2026-000044.1","url":null,"abstract":"<p><p>Recently, the pharmaceutical industry has recognized the benefits of assessing moisture by measuring the water activity of the product instead of its total water content. USP <922> has introduced water activity as a metric for determining the free, or \"active\", water that is available in a pharmaceutical product that can participate in undesired reactions such as hydrolysis or create an environment that supports microbiological growth. Traditional water content determination methods for lyophilized products, such as Karl Fischer titration, are time-consuming and measure the total water content which includes both the \"active\" and \"inactive\" water populations. In addition, the destructive nature of Karl-Fischer titration means that the moisture analysis of statistically relevant sample sets of lyophilized drug products is typically avoided, resulting in limited insight into the drying process and creating challenges for accurate determination of moisture specifications for product stability. Moisture assessment using water activity measurements, as mentioned in USP <922>, can be accomplished using newer non-destructive methods such as frequency modulated spectroscopy (FMS) headspace analysis. A moisture sorption isotherm can be used to bridge the measurements between the traditional Karl-Fischer total water content and the headspace water activity by establishing the relationship between the two for a particular drug product.In this study, a lyophilized product already in production was used as a model to evaluate this approach. Using a moisture sorption isotherm generated using a Dynamic Vapor Sorption (DVS) instrument, good correlation of the total water content of the lyophilized product was observed between the experimental Karl Fischer (KF) results and the values inferred from the FMS-Water Activity measurements. Due to the non-destructive nature of the headspace water activity analysis, rapid acquisition of a statistically relevant number of samples from three production batches were compared to demonstrate the robustness of this method for assessing moisture.</p>","PeriodicalId":19986,"journal":{"name":"PDA Journal of Pharmaceutical Science and Technology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148866349","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":"Analytical Characterization of Polymer Components in Parenteral Primary Packaging.","authors":"Will Parker, Dominik Quitmann, Ana Kuschel","doi":"10.5731/pdajpst.2026-000042.1","DOIUrl":"https://doi.org/10.5731/pdajpst.2026-000042.1","url":null,"abstract":"<p><p>Chemically crosslinked elastomers such as butyl rubber (IIR) and its halogenated derivatives (BIIR, CIIR) remain the benchmark for parenteral applications due to their exceptional gas barrier properties, chemical resistance, and long-term stability. Emerging materials, including brominated isobutylene-co-para-methylstyrene and thermoplastic elastomers (e.g., SEBS-based materials), offer architectural flexibility and processing advantages but require careful formulation to achieve equivalent sealing and barrier performance. The relationship between polymer composition, viscoelastic behavior, and functional sealing performance is examined using mechanical, thermal, rheological, and analytical characterization techniques. The paper further discusses product-level requirements, including compendial compliance, extractables and leachables (E&L) assessment with USP <1663>/<1664>, biocompatibility, and deterministic CCI testing in accordance with USP <1207> and global regulatory expectations. Special attention is given to time-dependent sealing behavior, residual seal force, pressure-induced stopper movement, and performance under cryogenic storage conditions relevant to advanced biologics and mRNA-based therapies. The evolution of risk-based extractables and leachables strategies, including threshold concepts (SCT, QT, AET) and advances in chromatographic and mass spectrometric methodologies, is also reviewed. Finally, the integration of finite element analysis, viscoelastic modeling, and mass migration simulation is presented as a predictive framework to complement empirical testing, reduce development complexity, and support science-based regulatory justification. Together, material science, analytical characterization, performance testing, and simulation-driven design form a holistic approach to developing robust, compliant, and future-ready elastomeric primary packaging components for sterile pharmaceutical products.</p>","PeriodicalId":19986,"journal":{"name":"PDA Journal of Pharmaceutical Science and Technology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148866269","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":"Quantifying User-Applied Forces on Prefilled Syringe Luer Cone: A Human Factors Ergonomics Study.","authors":"Esther Foo, Molly O'Mara, Charles L Mauro, Chris Morley, Oscar Frias, Aanal Patel, Jiaying Shen, Guangli Hu, Steven Persak","doi":"10.5731/pdajpst.2026-000038.1","DOIUrl":"https://doi.org/10.5731/pdajpst.2026-000038.1","url":null,"abstract":"<p><p>This study investigates the real-world forces and torques applied by professional healthcare users to the luer cone region of prefilled syringes (PFSs) during typical handling and preparation tasks. While standards such as ISO 11040-4 address mechanical robustness, limited data exist on the magnitude and nature of forces various users actually apply during device useÂinformation that is critical for ensuring patient safety and product reliability. To address this gap, a custom measurement platform replicating a 1.5 mL Luer Lock PFS, instrumented with multi-axis force and torque sensors was developed. Participants (n=60 nurses and retail pharmacists) performed key handling tasks, including unscrewing the tip cap, screwing on a needle, removing the needle cap, and activating the safety needle shield-while applied forces were recorded. Four safety needle types-two hinge-based, one slider-based, and one spring-based retractable mechanism-were included in the evaluation; all safety needles require users to actively deploy the safety guards. Tasks were completed under three instruction conditions: naturalistic use (\"actual\"), elevated force use (\"confident\"), and perceived upper-bound force (\"maximum acceptable\"). The results quantify the range and characteristics of user-applied forces across tasks, needle types, and instructional prompts, providing valuable data to inform technical specifications for luer cone interfaces. In addition, these findings highlight the importance of study design choices such as task selection and instructional prompting when conducting human factors force characterization studies intended to support robust, use-relevant specifications setting. These insights aim to support the development of PFS devices that are both robust and user-friendly, ultimately ensuring the devices designed are suitable for the capabilities of their intended users.</p>","PeriodicalId":19986,"journal":{"name":"PDA Journal of Pharmaceutical Science and Technology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148866324","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":"CQV Considerations for Single-Use Systems in Biopharmaceutical Manufacturing: A Practical Framework.","authors":"Gurinderpal Singh","doi":"10.5731/pdajpst.2026-000061.1","DOIUrl":"https://doi.org/10.5731/pdajpst.2026-000061.1","url":null,"abstract":"<p><p><i>Single-use systems (SUS) have become the dominant technology across the biotechnology and pharmaceutical industry, and viral vector manufacturing is no exception. The standard CQV framework, however, was designed and largely developed for stainless steel, fixed-equipment biopharmaceutical manufacturing. This creates real qualification gaps that the industry is currently solving inconsistently. This article proposes a structured, fit-for-purpose CQV approach built around three pillars specific to single-use Biopharmaceutical facilities: equipment qualification of single-use systems, supplier qualification as the foundation of SUS CQV, and a event-driven requalification strategy for single-use multi-product facilities. The framework is illustrated through a detailed qualification example for a single-use bioreactor and is positioned against the current regulatory landscape, including EU GMP Annex 1, 21 CFR 211.65, PDA Technical Report No 66 and FDA gene therapy CMC guidance</i>.</p>","PeriodicalId":19986,"journal":{"name":"PDA Journal of Pharmaceutical Science and Technology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148866335","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":"<i>Pseudomonas aeruginosa</i> contamination in purified water systems: case study in a pharmaceutical industry.","authors":"Larissa Moreira Ribeiro, Rafael Marques Pereira Poeys de Carvalho, Gustavo Luis de Paiva Anciens Ramos","doi":"10.5731/pdajpst.2026-000036.1","DOIUrl":"https://doi.org/10.5731/pdajpst.2026-000036.1","url":null,"abstract":"<p><p>Purified water is critical to the pharmaceutical industry. It is used at various stages of production and is subject to strict quality standards. This paper presents a case study of <i>Pseudomonas aeruginosa</i> microbiological contamination in a Brazilian pharmaceutical company's purified water generation and distribution system. The study investigates the causes of contamination, its microbiological and operational impacts on the production process, and the corrective and preventive measures adopted. The analysis involved examining internal documents, physicochemical and microbiological monitoring records, sanitation procedures, and system qualification reports. The results revealed operational failures during sanitation, mainly due to insufficient Standard Operating Procedures instructions for the aseptic handling of the mixed-bed resin and the risk of recontamination after system opening. The sanitizer that was routinely used, sodium metabisulfite, was ineffective at eliminating the microorganism and was replaced by peracetic acid, which eradicated the <i>P. aeruginosa</i> contamination. However, incompatibility of the new agent with system components was observed, which compromised water quality parameters. In conclusion, effective microbiological control requires efficient sanitizers, well-defined procedures, material compatibility, and alignment with good manufacturing practices. Additionally, the importance of continuous monitoring, a culture of quality, and structured change management to ensure sanitary industrial processes should be emphasized.</p>","PeriodicalId":19986,"journal":{"name":"PDA Journal of Pharmaceutical Science and Technology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148765959","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}