PDA Journal of Pharmaceutical Science and Technology最新文献

{"title":"Beyond Batch Release: Responsible Decision-Making, Professional Judgment, and Governance in Complex Pharmaceutical Manufacturing.","authors":"Mario Stassen","doi":"10.5731/pdajpst.2026-000016.1","DOIUrl":"10.5731/pdajpst.2026-000016.1","url":null,"abstract":"<p><p>Responsible decision-making in pharmaceutical manufacturing increasingly occurs within complex, distributed, and rapidly evolving environments. While the European Qualified Person (QP) holds defined regulatory accountability, modern decision contexts extend beyond compliance verification and require integration of scientific understanding, life cycle knowledge, and organizational governance. Building on recent discussions surrounding technological evolution and regulatory expectations, this review explores how professional judgment operates in environments characterized by uncertainty, accelerating timelines, and expanding organizational interfaces. Specification compliance alone often provides insufficient confidence for decision-making. Confidence increasingly emerges through process understanding, integration of multidisciplinary expertise, and development of coherent scientific interpretation connecting data, process behavior, and patient expectations. Accelerated environments also reveal how governance structures and organizational systems influence decision quality, highlighting the importance of clear accountability, trusted expertise, and independent judgment. This paper introduces the concept of <i>patient-relevant decision quality</i> and discusses how experienced professionals contribute to the continuity of understanding across life cycle stages. Although advanced analytical tools and emerging digital capabilities increasingly support process interpretation and decision-making, responsible decisions within GMP environments remain anchored in professional judgment, organizational governance, and regulatory accountability. Seen through this lens, the QP represents one perspective within a broader system of responsible decision-making in which organizational maturity, principled leadership, and stewardship of judgment support scientifically grounded and ethically sound outcomes.</p>","PeriodicalId":19986,"journal":{"name":"PDA Journal of Pharmaceutical Science and Technology","volume":" ","pages":"343-348"},"PeriodicalIF":0.0,"publicationDate":"2026-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147717642","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":"Redecorating the Decision Tree.","authors":"James Agalloco","doi":"10.5731/pdajpst.2026-000001.1","DOIUrl":"10.5731/pdajpst.2026-000001.1","url":null,"abstract":"","PeriodicalId":19986,"journal":{"name":"PDA Journal of Pharmaceutical Science and Technology","volume":" ","pages":"349-352"},"PeriodicalIF":0.0,"publicationDate":"2026-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147778126","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":"Determination of Trace Nitrosamines in Plastic Pharmaceutical Packaging Materials.","authors":"Lukas Jost, Frank Sprau, Lukas Thörner, Annie Wan, Payden Trujillo, Shiwei Zhou, Lucas Shaner, Ethan Li, Bilig Sechin, Lars Gläser, David Young, Percy Kampeis, Weichun Yang","doi":"10.5731/pdajpst.2025-000072.1","DOIUrl":"10.5731/pdajpst.2025-000072.1","url":null,"abstract":"<p><p>Nitrosamines are classified as probable (IARC Group 2 A) or possible (IARC Group 2B) human carcinogens, capable of inducing tumors even at very low concentrations (nanogram per liter levels). Regulatory considerations specifically affect large volume parenteral (LVP) products due to the high application volume combined with very low allowable intake limits. These compounds have already attracted significant attention for elastomer materials like rubber. A recent FDA communication highlighted the particular importance of infusion bags, given their unique nature. In this study, over 300 batches of plastic materials, used for LVP packaging, were tested, and trace levels of nitrosamines at nanogram per liter scale were detected in several plastic granules and films. These results indicated the importance of nitrosamine profiling during raw material qualifications for LVP products.</p>","PeriodicalId":19986,"journal":{"name":"PDA Journal of Pharmaceutical Science and Technology","volume":" ","pages":"298-311"},"PeriodicalIF":0.0,"publicationDate":"2026-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147474969","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":"Application of Stage 3a Heightened Monitoring to Close Process Knowledge Gaps of Legacy Injectable Products: A Commercial Scale Case Study.","authors":"Ajay Babu Pazhayattil, Avinash Joshi, Marzena Ingram","doi":"10.5731/pdajpst.2026-000006.1","DOIUrl":"10.5731/pdajpst.2026-000006.1","url":null,"abstract":"<p><p>Legacy sterile injectable products developed prior to the widespread adoption of Quality by Design (QbD) principles are often entered into the product life cycle with a limited quantitative understanding of process variability. The U.S. Food and Drug Administration's (FDA's) Process Validation Guidance (2011) recognizes Stage 3 continued process verification (CPV) as a life cycle activity and introduces heightened monitoring as a mechanism to establish a statistically meaningful baseline prior to routine monitoring. Industry has termed the two CPV sub-stages as Stage 3a and 3b. Published examples describing structured Stage 3a execution for commercial legacy injectables remain limited. This article presents a commercial-scale case study describing the design, execution, and outcomes of a Stage 3a monitoring program for a lyophilized injectable product. A risk based, statistically justified sampling strategy was implemented across multiple commercial batches to quantify intra and inter batch variability, evaluate spatial variability within the lyophilizer, and assess time-dependent degradation risks. Variance component analysis, regression analysis, and process capability metrics were applied to both historical and Stage 3a data. Results identified the total manufacturing time from active pharmaceutical ingredient (API) addition through filling as a parameter strongly correlated with impurity variability. The Stage 3a program enabled conversion of previously assumed controls into measurable and trended parameters and supported development of a data-driven Stage 3b monitoring strategy aligned with FDA and International Conference for Harmonisation (ICH) life cycle validation principles. This case study illustrates how Stage 3a can be effectively leveraged to close residual process knowledge gaps for legacy sterile injectable products.</p>","PeriodicalId":19986,"journal":{"name":"PDA Journal of Pharmaceutical Science and Technology","volume":" ","pages":"353-371"},"PeriodicalIF":0.0,"publicationDate":"2026-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147717677","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":"Pinch Force Endurance and Usability Considerations for Pre-Filled Syringe Designs Used by Chronic Obstructive Pulmonary Disease Patients.","authors":"Xueke Wang, Jaclyn Baron, Joanna So, Laura Morton, James Hoare, Julian Dixon, Sherri Biondi","doi":"10.5731/pdajpst.2025-000049.1","DOIUrl":"10.5731/pdajpst.2025-000049.1","url":null,"abstract":"<p><p>Prefilled syringes (PFSs) are commonly used for self-administered injectable drugs, particularly for chronic conditions. A critical design factor is the injection force needed to depress the plunger, which varies by drug viscosity and syringe mechanics. This is especially important for patients with potential strength limitations. Human factors studies help evaluate these physical demands to ensure PFSs can be used safely and effectively across diverse users. Assessing both maximum force capabilities and endurance provides key insights for optimizing syringe design and minimizing patient discomfort. This study evaluated chronic obstructive pulmonary disease (COPD) patients' experience with PFS samples of varying injectability (injection force and duration) and measured pinch force endurance-an indicator for PFS physical demand. Those insights aimed to guide PFS design for users with strength limitations. Forty-two COPD patients performed simulated injections using three PFS samples (28 N, 37 N, 47 N force) and rated perceived demand. They also measured pinch force endurance by gripping a surrogate PFS device at 28 N and at their maximum voluntary force. Data predicted the 5th percentile pinch force endurance for COPD patients. The estimated COPD patients' 5th percentile pinch force endurance at 28 N was 16 seconds. Notably, when asked to push at their maximum pinch force, COPD patients' endurance was around 4.4 seconds. Males pinched and held 28 N longer than females, but no gender difference was observed at the maximum force. Endurance decreased as required force approached maximum capacity (consistent with Rohmert's Curve). PFS usage can be challenging for users with strength limitations. A 28 N force was sustainable for 16 seconds for 95% of COPD patients. Developers should minimize injection force where possible and accommodate varied injection styles-lower forces improve endurance, aiding users with reduced strength. These findings support designing accessible PFSs for diverse populations.</p>","PeriodicalId":19986,"journal":{"name":"PDA Journal of Pharmaceutical Science and Technology","volume":" ","pages":"312-327"},"PeriodicalIF":0.0,"publicationDate":"2026-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147474086","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":"Impact of Storage Orientation and Duration on Prefilled Syringe Performance: Break-Loose and Glide Forces, and Injection Time Across Multiple Time Points.","authors":"Vincent Mensah, Samira Munkaila, Hao Wang, Björn-Hendrik Peters, George Currier, Christina Evans, Yusuf Oni, Ankur Kulshrestha, Olga Yee, Joseph Rinella, Trella Mitchell","doi":"10.5731/pdajpst.2025-000069.1","DOIUrl":"https://doi.org/10.5731/pdajpst.2025-000069.1","url":null,"abstract":"<p><p>This study investigates the dynamics of break loose glide force (BLGF) in prefilled syringes (PFS) and injection time in autoinjectors (AI) across different orientations and time points, focusing on their impact on drug delivery performance. PFS and Autoinjectors are pivotal in modern therapeutics, enabling precise administration of biologics, vaccines, and other sensitive pharmaceuticals. Patients with chronic conditions and individuals with limited dexterity requiring frequent self-administration, all benefit from devices that minimize BLGF to ensure consistent injection times. To explore the influence of storage orientation (tip-up vs. tip-down) and time on these devices, we conducted a comprehensive evaluation over a 12-month period supplemented by reference timepoint samples. Utilizing a dual-orientational framework, PFS and autoinjectors were stored under controlled conditions to assess orientation-dependent performance. Aged and empty samples served as reference controls. The study's primary metrics included BLGF, which is the initial force required to initiate plunger movement then enable injection along the barrel, and injection time. These parameters were analyzed using a calibrated Zwick/Roell mechanical tester under controlled environmental conditions.Key findings reveal statistically significant but not practically impactful effects of storage orientation on BLGF or injection time across all tested intervals. Minor time-based variations were noted, with BLGF shifts being less than 1 N and injection time deviations under 2 seconds. These changes indicated no practical significance or risk of out-of-specification performance. The Analysis of variance (ANOVA) analysis confirmed no evidence suggesting orientation affects functionality.This work demonstrates that short to mid-term storage conditions do not adversely affect device performance, providing critical assurance for manufacturers, regulators, and end-users. The study highlights the robustness of PFS and Autoinjectors against orientation and temporal changes, mitigating risks associated with handling variability and optimizing supply chain logistics. Future research should extend these findings to longer durations to confirm long-term stability.</p>","PeriodicalId":19986,"journal":{"name":"PDA Journal of Pharmaceutical Science and Technology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148144271","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":"Development, Validation, and Implementation of a Pharmaceutical Facility Disinfection Program.","authors":"James Polarine, Matt Hofacre, Tony Cundell","doi":"10.5731/pdajpst.2025-000087.1","DOIUrl":"https://doi.org/10.5731/pdajpst.2025-000087.1","url":null,"abstract":"<p><p>Maintaining microbial control in pharmaceutical manufacturing environments is a cornerstone of Good Manufacturing Practices (GMP). This comprehensive review outlines the development, validation, and implementation of robust cleaning and disinfection programs for pharmaceutical facilities, including cleanrooms, Restricted Access Barrier Systems (RABS), and isolators. The article integrates regulatory expectations from U.S. FDA (21 CFR 211), EU GMP Annex 1, and industry guidance documents such as USP <1072>, PDA TR70, and IEST RP 18.5, emphasizing the importance of both laboratory-based disinfectant efficacy studies and in situ field trials. Key topics include the selection and rotation of disinfectants and sporicidal agents, validation methodologies, environmental monitoring strategies, and the role of Vaporized Hydrogen Peroxide (VHP) in bio-decontamination. Case studies and data-driven insights illustrate best practices for ensuring contamination control, including equipment cleaning validation and requalification protocols. The article advocates for a sound approach to validate both manual and automated disinfection technologies, offering a forward-looking perspective on contamination control in modern pharmaceutical manufacturing.</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":"147777761","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":"Evaluation of the Effect of Single-Temperature Incubation on the Recovery and Behavior of Microbiota in the Context of Environmental Monitoring.","authors":"Laura Bailac, Laura Arnaldi, Lisa Mallam, Laurent Leblanc","doi":"10.5731/pdajpst.2025-000051.1","DOIUrl":"https://doi.org/10.5731/pdajpst.2025-000051.1","url":null,"abstract":"<p><p>Environmental monitoring is essential for the prevention and control of microbial contamination. Accurate and reproducible monitoring is critical, and standardized precise conditions of incubation in regulatory documents for environmental sampling are still lacking. This study investigated microbial recovery and growth dynamics under a controlled single-temperature incubation setting (25°C, 27.5°C and 30°C) across 83 microbial agents (49 bacteria, 24 molds and 10 yeast strains). We showed that at the temperature of 25°C, all microbial strains investigated were recovered. Elevated incubation temperatures did not alter the recovery of bacteria and yeast strains but affected the recovery and recovery rate of specific mold strains. In addition, time-to-result (TTR), defined as the time necessary for 90% colony recovery, varied with incubation temperatures and microbiota. It decreased with increasing temperature for all bacterial strains tested, while showing more complex patterns for molds. Altogether, our results contribute valuable insights into microbial ecology and highlight the complex interaction between temperature and microbial behavior. This study emphasizes the necessity for precise temperature regulation in microbial culture methodologies for accurate and reproducible environmental monitoring.</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":"147777819","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":"Gamma Irradiation of Ready-to-Use Injectable Aqueous Suspensions: Impact on Particle Size, Rheology, Interfacial Properties, and Polymer Stability.","authors":"Swetha Ainampudi, Matthew Zajac, Sushesh Srivasta Palakurthi, Dimple Modi, Lenora Dieyi, Stephanie Lam, Sriramakamal Jonnalagadda","doi":"10.5731/pdajpst.2026-000023.1","DOIUrl":"https://doi.org/10.5731/pdajpst.2026-000023.1","url":null,"abstract":"<p><p>Ready-to-use (RTU) long-acting injectable aqueous suspensions offer sustained drug release but present significant challenges for terminal sterilization. While aseptic processing is frequently used for suspension manufacturing, it lacks the sterility assurance of terminal sterilization. This work investigated the viability of gamma sterilization of model RTU aqueous suspensions containing varying polymer types and suspended drug loads. Comprehensive physicochemical characterization revealed that gamma irradiation did not affect the drug solid-state form in both model suspensions, and effectively stabilized particle size, notably stopping particle size growth observed in the non-irradiated GSK model suspension (control group). However, size exclusion chromatography (SEC) and HPLC analyses confirmed significant radiolytic degradation of polymeric surfactants and stabilizers (poloxamer 338 and PEG 3350) in both naproxen and GSK model suspensions, characterized by random chain scission and cross-linking of the polymer chains. This polymer degradation induced by radiolysis resulted in a measurable reduction in viscosity and injection force, thereby easing the force required to push suspension through the narrow needle bore of the syringe. Conversely, radiolysis-induced loss of suspension microstructure compromised long-term physical stability (resuspendability), leading to irreversible caking after 18 months of storage. These findings indicate that while gamma irradiation is a plausible terminal sterilization method for injectable suspensions, careful consideration must be given to formulation design to compensate for radiolytic polymer degradation and maintain suspension physical stability over the desired shelf life.</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":"147777849","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":"Thoughts on the Use of Prior Knowledge in Managing the Patient Safety Risk of Extractables and Leachables from Packaging Systems and Manufacturing Components/Systems.","authors":"Dennis Jenke","doi":"10.5731/pdajpst.2026-000017.1","DOIUrl":"https://doi.org/10.5731/pdajpst.2026-000017.1","url":null,"abstract":"<p><p>According to the current Stage 2b version of ICH Q3E, \"the quality risk management process for E&L warrants a holistic strategy, leveraging prior knowledge â¦\" where prior knowledge is that knowledge (or information) which is available to support the quality risk management of E&L prior to the initiation of the risk management process. As envisioned in Q3E, prior knowledge is a powerful resource.In this Correspondence I consider the use of prior knowledge in extractables and leachables (E&L) safety risk management and suggest how prior knowledge can be used in effective and efficient safety risk assessment.</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":"147778102","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}