PDA Journal of Pharmaceutical Science and Technology最新文献

{"title":"Automated Surface Swab Sampling: A Statistical Comparison of a Novel Approach to Existing Methods.","authors":"Nicole Collier, Michael Lund, Keith Bader, Richard Mineo","doi":"10.5731/pdajpst.2025-000005.1","DOIUrl":"https://doi.org/10.5731/pdajpst.2025-000005.1","url":null,"abstract":"<p><p>Analytical testing and an appropriate sampling method are instrumental in confirming that equipment surfaces have been adequately cleaned during cleaning validation or verification activities. The sampling method is critical to generating accurate results. Regulatory Health Authorities (RHA) expect manufacturers to employ rinse, surface swab, or a combination of the two, with one favoring swab sampling methods. Surface swab sampling is performed manually by directly holding the swab (hand swabbing) or attaching the swab to the end of an extension pole (remote swabbing). Remote swabbing is an alternative for cases where equipment surfaces to be sampled are not readily accessible and would otherwise require confined space entry. This study evaluated the performance of a prototype automated swabbing device constructed from configurable microcontrollers, microelectronics, and electromechanical components against representative manual sampling methodologies.The automated swabbing device was designed and built to automate the swabbing work process for surfaces exhibiting various accessibility issues and challenges. Automated swab sampling of pharmaceutical manufacturing equipment offers several advantages over hand swabbing or remote swabbing, including decreased variability, the necessity for swab qualification of operators, increased accuracy versus remote swabbing, and decreased risk to personnel.To determine if automated swabbing can replace the current state of the art in manual swabbing, Hyde Engineering + Consulting performed a comparative analysis of manual swabbing methods, hand and remote, and an automated swabbing method using a prototype device developed by Swabbot Solutions. This case study evaluated the three swabbing methods using multiple replicates, concentrations, representative soils, and controls to gauge the relative recovery performance of the accuracy and variability of each method.The study showed that the automated swabbing device achieved comparable recovery levels to the hand swabbing method but with lower variability. The remote swabbing method exhibited higher variability and lower recovery levels statistically dissimilar to both hand and automated swabbing methods. Based on these performance results, we concluded that an automated swabbing method is an acceptable alternative to hand swabbing and outperforms the remote swabbing method.</p>","PeriodicalId":19986,"journal":{"name":"PDA Journal of Pharmaceutical Science and Technology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144643104","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":"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 Schaeffer, Alex Gadberry, Jennifer Nicole Earley, Mithun N Thimonthy, Kelvin H Lee","doi":"10.5731/pdajpst.2024-003037.1","DOIUrl":"https://doi.org/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 (<i>e.g.,</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) sponsored 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":""},"PeriodicalIF":0.0,"publicationDate":"2025-07-15","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":"Economic Advantages of Original Container Closure Systems in Combination Product Development: Scenarios with Expert Validation and Industry-Quantified Cost-Time Savings.","authors":"Mehul Desai, Daniel Waites, William Rich, Lawton Laurence, Shirish Ingawale, Fran DeGrazio","doi":"10.5731/pdajpst.2025-000002.1","DOIUrl":"https://doi.org/10.5731/pdajpst.2025-000002.1","url":null,"abstract":"<p><p>Many on-body delivery systems (OBDSs) for subcutaneous (SC) delivery require a change in primary container closure system (CCS). This necessitates compatibility and stability testing with original packaging materials and distribution and assembly, which are often laborious and time-consuming. Exploring new primary CCSs rather than using an original CCS can introduce risks, prolong timelines, and increase costs. In this study, 21 US-based combination product experts completed a double-blinded online survey between 6 October and 20 November 2023. The survey included 15 screening questions and 23 survey questions, including questions about compatibility issues between new CCSs and drugs and stability testing for new CCSs. The largest proportion of participants (28.6%) reported that 5-10% of products they had worked directly on had experienced compatibility issues between a new CCS and a drug, with a weighted average of 11.9%. The most common compatibility issues were particulate challenges in 55.6%, sterility in 27.8%, and leachables in 16.7%. Most respondents (76.2%) rated the timeline showing that using an OCC can save 12-24 months as somewhat (38.1%) or very (38.1%) representative. Most participants (57.1%) estimated that the range of direct costs, including development costs, drug product, engineering runs, line changes, and other costs, when using an OBDS with a new CCS is $1015 million, 38.1% estimated <$10 million, and 4.8% estimated $2125 million. Most participants (80.9%) reported that challenges in the primary CCS qualification/validation process delay entry of combination products into clinical trials or delay their commercial launch. The weighted average of the delay was 9.7 months. Using an original CCS during combination product development would therefore be of significant economic benefit to the development of combination products in terms of time, cost, and risk.</p>","PeriodicalId":19986,"journal":{"name":"PDA Journal of Pharmaceutical Science and Technology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144310295","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":"Reply to commentary on  Understanding the Non-Equivalency of Bio-Fluorescent Particle Counts versus the Colony Forming Unit.","authors":"Mike Dingle, Jim Cannon, Chris Knutsen, Kim Perkins, Patrick Hutchins, Margit Franz-Riethdorf, Phil Villari","doi":"10.5731/pdajpst.2025-000024.1","DOIUrl":"https://doi.org/10.5731/pdajpst.2025-000024.1","url":null,"abstract":"","PeriodicalId":19986,"journal":{"name":"PDA Journal of Pharmaceutical Science and Technology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144310299","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":"Ensuring Robust Drug Delivery: A Comprehensive Study on the Mechanical and Chemical Performance of 3 ml RTU Cartridges.","authors":"Robert Lindner, Daniele Zuccato, Volker Rupertus","doi":"10.5731/pdajpst.2025-000016.1","DOIUrl":"https://doi.org/10.5731/pdajpst.2025-000016.1","url":null,"abstract":"<p><p>Driven by more patient-centric at-home treatments, the pharmaceutical industry is shifting toward subcutaneous drug formulations, particularly for biologics. This aids in simplifying patient self-administration, improving adherence, and reducing healthcare costs. Hence, there is an increasing need for optimized drug containment systems, as these will frequently be used by non-professionals in home settings. This study evaluates the break-loose and gliding forces (BLGF) as well as the inorganic and organic leachable profiles of cartriQ® 3 mL ready-to-use (RTU) cartridges to ensure safe and effective drug delivery. The cartridges, made from FIOLAX® clear Type I borosilicate glass, underwent hot forming into tubular cartridges, ensuring a hydrolytic resistance of not more than 80% of the ISO 4802-1 limit, followed by washing, siliconization, and steam sterilization. Testing was conducted after accelerated aging over up to 24 weeks at 40°C using ultrapure water, histidine buffer, and phosphate buffer as model solutions. Key performance metrics, including BLGF, siliconization performance, and levels of inorganic leachables, e.g., boron, sodium, silicon, and select organic leachables, were assessed following ISO 21881 and ICH Q3D guidelines.</p>","PeriodicalId":19986,"journal":{"name":"PDA Journal of Pharmaceutical Science and Technology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144310296","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":"Nitrogen Dioxide sterilization follows log-linear microbial inactivation kinetics using Geobacillus stearothermophilus biological indicators.","authors":"Thomas P Richards, Delaney Lisco, Tiffany Bianchi, Gabriele Shahine, Huyen Nyugen, Natalie Simmons, Sylvie Dufresne, David Opie","doi":"10.5731/pdajpst.2024.012997","DOIUrl":"https://doi.org/10.5731/pdajpst.2024.012997","url":null,"abstract":"<p><strong>Aim: </strong>The primary purpose of this study was to determine the inactivation kinetics of <i>Geobacillus stearothermophilus</i> biological indicators (BIs) exposed to Nitrogen Dioxide (NO₂) gas in the presence of humidity.</p><p><strong>Methods: </strong>BIs inoculated with 6 log₁₀ <i>G. stearothermophilus</i> spores were used as a test substrate. Three BI Lots manufactured from each of three different BI spore crops were evaluated. Test cycles were run at room temperature with 80% relative humidity. Direct Enumeration methods were used to quantify the resistance of spores with surviving populations greater than 2 log₁₀ Fraction Negative methods were used to calculate spore populations in the quantal region. The methods were combined in order to show spore inactivation from 6 log₁₀ to approximately -2 log₁₀ The D-Value and least-squares regression (R²) were calculated.</p><p><strong>Results: </strong>Over 100 Direct Enumeration and Fraction Negative Cycles were completed at a fixed NO₂ concentration varying only time. Critical process parameters were maintained over all cycles. Empirical data confirmed a log-linear relationship over an 8 log₁₀ population range with R² values greater than 0.8, allowing for extrapolation of the curve to -6 log₁₀ Study outcomes were comparable for all manufactured BI Lots.</p><p><strong>Conclusions: </strong>NO₂ sterilization follows first-order log-linear microbial inactivation kinetics, which is consistent with a mechanism of action based on a single active species.</p><p><strong>Significance and impact of study: </strong>This is the first study to report on the microbial inactivation kinetics of NO₂ sterilization. Further, this is one of the few studies to demonstrate inactivation kinetics applying ISO methodology.</p>","PeriodicalId":19986,"journal":{"name":"PDA Journal of Pharmaceutical Science and Technology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144310297","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":"Biological Indicators, Process Lethality and Vapor Phase Hydrogen Peroxide Processes.","authors":"James Agalloco","doi":"10.5731/pdajpst.2024-003033.1","DOIUrl":"https://doi.org/10.5731/pdajpst.2024-003033.1","url":null,"abstract":"<p><p>This manuscript reviews the similarities between death curves associated with 'rogue' biological indicator results in vapor phase hydrogen peroxide decontamination / sterilization processes and those expected from varying process conditions. The manuscript considers whether the perceived 'rogue' behavior of some biological indicators in these process may be the result of the phase differences. Consideration of 'wet' vs 'dry' processes are discussed and recommendations for process improvement to reduce failures are provided.</p>","PeriodicalId":19986,"journal":{"name":"PDA Journal of Pharmaceutical Science and Technology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144310294","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":"Quality Risk Management for Isolator Gloves.","authors":"Andreas Kindscher, Richard Denk, Chris Burns, Rico Schulze","doi":"10.5731/pdajpst.2025-000029.1","DOIUrl":"https://doi.org/10.5731/pdajpst.2025-000029.1","url":null,"abstract":"<p><p>This article focuses on describing control measures intended to reduce the risk of glove damages, which can be linked to contamination (particulate, microbiological). Specific risks involving gloves are analysed, assessed and minimized by means of appropriate control measures. The aim is to demonstrate that the risk of contamination via isolator gloves cannot be mitigated by a single action, but rather that a combination of several preventative measures is required.Important control measures for safe handling of gloves at barrier systems include the observation of glove functional use, personnel training and monitoring control measures. This observation of the glove functional use can represent a higher or lower GMP risk for the product depending on the intervention.The handling of the gloves and their use should be documented accordingly and evaluated in a risk assessment. The risk analysis defines measures that are part of the Quality Risk Management for Gloves and contribute to the safe production of sterile pharmaceuticals.This raises the question as to the point from which an isolator is at risk of microbiological contamination following damage to a glove, or what size of pinhole in a glove represents a risk. This article works on the assumption that this question can only be answered by means of glove quality risk management.</p>","PeriodicalId":19986,"journal":{"name":"PDA Journal of Pharmaceutical Science and Technology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144310298","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":"Worldwide Regulatory Reliance: Results of an Executed Chemistry, Manufacturing, and Control Post-Approval Change Pilot.","authors":"Cynthia Ban, Jamie Graham, Lyne Le Palaire, Priya Persaud, Franziska Brehme, Olivier Faure, Allison Rameau, Ana Luisa Silva","doi":"10.5731/pdajpst.2024-003023.1","DOIUrl":"10.5731/pdajpst.2024-003023.1","url":null,"abstract":"<p><p>Post-approval changes (PACs) are integral to pharmaceutical product life cycle management, ensuring that the product remains safe, effective, and compliant with evolving standards. However, managing these changes across multiple regulatory jurisdictions remains a challenging endeavor due to diverse regulatory requirements and timelines across national regulatory authorities (NRAs). This results in delays in obtaining approval from NRAs, impacting global supply chains and ultimately jeopardizing timely access to essential medical products by patients. In 2021, the World Health Organization issued the Good Reliance Practices (GReIP) guidance to encourage streamlined PAC review and approval process while maintaining access to quality-assured, safe, and effective medicinal products. NRAs are encouraged to rely on the assessment completed by a reference authority that agrees to provide the outcomes of its regulatory expertise. The ultimate objective of this guidance is to accelerate the overall process for PACs, ultimately fostering more equitable and timely access to medical products by the populations who need them. This approach was tested in a chemistry, manufacturing, and control PAC pilot to determine the feasibility of using the principles of regulatory reliance based on the recommendations outlined in the GReIP with the goal of establishing a predictable, 6-month approval timeframe across multiple NRAs. The design and management of this pilot is described in Gastineau et al. This paper describes the outcomes of the pilot, which demonstrated that regulatory reliance is feasible. Of the 21 NRAs that agreed to participate, 55% were able to complete the review within 6 months; within 10 months, 95% of approvals were received and, after 16 months, all participating countries had approved the PAC. The use of a Q&A SharePoint Tool allowed for visibility of the questions raised and the company responses among the NRAs. Feedback on this reliance pilot was solicited from the participating NRAs and provides further support for future CMC PAC reliance cases.</p>","PeriodicalId":19986,"journal":{"name":"PDA Journal of Pharmaceutical Science and Technology","volume":" ","pages":"295-302"},"PeriodicalIF":0.0,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144028288","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":"Mechanical Container Closure Integrity Test: A Method for Cartridge Systems.","authors":"Michael W Foubert, Benoit Lux, Julie Bourguard, Lucas Schultz, Meng John Zhao, Jason D Marlin, Matthew S Huser, Henri Hebting, Lei Li","doi":"10.5731/pdajpst.2024.012941","DOIUrl":"10.5731/pdajpst.2024.012941","url":null,"abstract":"<p><p>A cartridge container closure integrity control strategy may leverage a combination of test methods to ensure that drug products in the assembled container system are protected from an exchange with the external environment. These methods provide evidence supporting the suitability of the container closure system; however, some methods involve extended test times, complex setups, subjective interpretation, and are destructive. A method that mitigates such factors was developed to improve upon testing utilized within the control strategy. Reviewing the underlying principles of internal methods and external standards resulted in two potential paths, a force decay method and a constant force method, to improve on the cartridge control strategy using a linear mechanical testing system. The force decay method monitors the force decay signal obtained from applying a predetermined force and holding the displacement constant for a desired time frame. The constant force method monitors the displacement signal obtained from applying a predetermined force and holding the force constant for a desired time frame. Supplementing the experimental data generated by both methods with a finite element analysis along with a first principles derivation of the system response aided in a recommendation to utilize the constant force method for cartridge container closure integrity leak testing. The constant force method was then optimized to attain the best signal response for leak detection and ensure a robust method. The data generated in this article support the viability of using the constant force mechanical container closure integrity test method for improving the in-process container closure integrity testing strategy for solution products.</p>","PeriodicalId":19986,"journal":{"name":"PDA Journal of Pharmaceutical Science and Technology","volume":" ","pages":"303-319"},"PeriodicalIF":0.0,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144023092","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}