PDA Journal of Pharmaceutical Science and Technology最新文献

{"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}

{"title":"Redecorating the Decision Tree.","authors":"James Agalloco","doi":"10.5731/pdajpst.2026-000001.1","DOIUrl":"https://doi.org/10.5731/pdajpst.2026-000001.1","url":null,"abstract":"<p><p>This manuscript reviews the history of terminal sterilization regulation and process expectations. Practices for this culminated in the EMA / PIC/S Decision Trees (EMA/CHMP/CVMP/QWP/850374/2015, March 2019) which outlines recommended process choices for steam and other sterilization methods. That guidance document is contrary to the recommendations included in USP <1229> Sterilization of Compendial Materials. This manuscript supports a preference for the more flexible approach to sterilization cycle development and validation provided in the USP general chapter.</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":"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":"Global health authorities review and approval trends for CMC post approval changes 2018-2024.","authors":"Karim Kacimi, Sunny Kamlesh Dave, Scott Roberts","doi":"10.5731/pdajpst.2025-000081.1","DOIUrl":"https://doi.org/10.5731/pdajpst.2025-000081.1","url":null,"abstract":"<p><p>The approval and implementation of Chemistry, Manufacturing, and Control (CMC) post-approval changes (PACs) by global health authorities are often lengthy and unpredictable in terms of requirements and timeline, potentially leading to drug shortages and hindering innovation in product quality and manufacturing processes. This study analyzes the review and approval times for CMC PACs from 2018 to 2024, focusing on alignment with the World Health Organization (WHO) recommendations for a maximum six-month review period for PACs. The analysis reveals a positive trend towards shorter approval times, with significant improvements observed post-2019. However, inconsistencies remain, particularly in the classification and procedural processes of CMC PACs across different countries. The study underscores the need for global harmonization of PAC frameworks and the adoption of WHO reliance principles to enhance the predictability of and efficiency of CMC lifecycle management. These improvements are crucial for strengthening the global supply chain, fostering innovation in pharmaceutical manufacturing, and ultimately ensuring timely patient access to essential medications.</p>","PeriodicalId":19986,"journal":{"name":"PDA Journal of Pharmaceutical Science and Technology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147777841","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

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

{"title":"Beyond Batch Release: Responsible Decision-Making, Professional Judgement, and Governance in Complex Pharmaceutical Manufacturing.","authors":"Mario Stassen","doi":"10.5731/pdajpst.2026-000016.1","DOIUrl":"https://doi.org/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, lifecycle knowledge, and organisational governance. Building on recent discussions surrounding technological evolution and regulatory expectations, this review explores how professional judgement operates in environments characterised by uncertainty, accelerating timelines, and expanding organisational 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 narratives that connect data, process behaviour, and patient expectations. Accelerated environments also reveal how governance structures and organisational systems influence decision quality, highlighting the importance of clear accountability, trusted expertise, and independent judgement.This paper introduces the concept of <i>patient-relevant decision quality</i> and discusses how experienced professionals contribute to continuity of understanding across lifecycle stages. Seen through this lens, the QP represents one perspective within a broader system of responsible decision-making, where organisational maturity, principled leadership, and stewardship of judgement support scientifically grounded and ethically sound outcomes.</p>","PeriodicalId":19986,"journal":{"name":"PDA Journal of Pharmaceutical Science and Technology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"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":"Comparative Study of Matrix vs. Product-Specific Cleaning Validation Approaches.","authors":"Mahender Boyapally","doi":"10.5731/pdajpst.2026-000007.1","DOIUrl":"https://doi.org/10.5731/pdajpst.2026-000007.1","url":null,"abstract":"<p><p>Cleaning validation is an essential part of the present Good Manufacturing Practices (cGMP) of the pharmaceutical industry. This comparison paper discusses two main cleaning validation methods: the matrix (worst-case) approach and product-specific approach. The paper assesses the strengths, weaknesses, risk profiles and real-world application of both methodologies through the review of regulatory guidance, industry best practices, and case study findings. The matrix approach, which justifies cleaning according to worst-case scenarios of groups of related products, is highly resource-efficient though it calls for hard scientific justification. The product-specific method offers wholesome validation of every product transition but requires enormous resources. The present study is a framework of the choice of the proper validation strategy depending on the features of the facilities, the complexity of the products portfolio, and the results of the risk assessment. This analysis suggests that a combined strategy, comprising factors of both methodologies with visible residue limits (VRL) as a risk-based instrument, may provide an effective balance between regulatory compliance and operational performance.</p>","PeriodicalId":19986,"journal":{"name":"PDA Journal of Pharmaceutical Science and Technology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147717657","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"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":"https://doi.org/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 lifecycle with a limited quantitative understanding of process variability. FDA's Process Validation Guidance (2011) recognizes Stage 3 continued process verification (CPV) as a lifecycle activity and introduces Stage 3a heightened monitoring as a mechanism to establish a statistically meaningful baseline prior to routine monitoring (Stage 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 total manufacturing time from API addition through filling as a key contributor to impurity variability and revealed a reproducible shelf specific assay trend. 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 ICH lifecycle 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":""},"PeriodicalIF":0.0,"publicationDate":"2026-04-18","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}