PDA Journal of Pharmaceutical Science and Technology最新文献

{"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}

{"title":"Viral Safety Reloaded-Insights from PDA's Virus Conference Around the Finalized ICH Q5A (R2) and NGS Workshop.","authors":"Sebastian B Teitz, Andy Bailey, Johannes Blümel, Arifa Khan, Alison Armstrong, Thomas R Kreil, Tomoko Hongo-Hirasaki, Remo Leisi, David Cetlin, Chakameh Azimpour, Sean O'Donnel, Simone Olgiati","doi":"10.5731/pdajpst.2025-000009.1","DOIUrl":"https://doi.org/10.5731/pdajpst.2025-000009.1","url":null,"abstract":"","PeriodicalId":19986,"journal":{"name":"PDA Journal of Pharmaceutical Science and Technology","volume":"79 3","pages":"337-354"},"PeriodicalIF":0.0,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144209123","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":"Coring and Fragmentation of Elastomeric Needle Shield in a Pre-Filled Syringe.","authors":"Sahab Babaee, Sean Teller, Kavin Kowsari, Nikolaos Vasios, Steven C Persak, Nagi Elabbasi, Guangli Hu","doi":"10.5731/pdajpst.2024-003041.1","DOIUrl":"10.5731/pdajpst.2024-003041.1","url":null,"abstract":"<p><p>Elastomeric components such as closures and stoppers play key roles in providing container closure integrity (CCI), supporting a portfolio of injectable combination products and primary containers including needle shields (NSs) in prefilled syringes (PFSs). Upon piercing through the elastomeric (i.e., synthetic rubber) components, the physical interaction between the needle and the deformable elastomer could result in the formation of small, random-shaped particles fragmented and dislodged from the NS material due to cutting processes. This phenomenon, called coring, poses a major risk in drug product contamination, as elastomer particle fragments can potentially be aspirated with the medication and injected into a patient or prevent injection. Here, we present a combined computational and experimental approach to assess the incidence of coring. In particular, we first experimentally characterized the nonlinear finite deformation behavior of five commonly used NS elastomers and calibrated constitutive models. Then, we performed finite element simulations validated with needle insertion experiments to compare the coring behavior of the NS elastomers. We demonstrated that higher maximum failure strain under tension and higher deformation-stiffening properties of the elastomer are contributing factors that attenuate coring and fragmentation. The experimental-numerical framework presented is suitable for quantifying broad correlative and discovering relationships between device properties governing the incidence of coring and fragmentation.</p>","PeriodicalId":19986,"journal":{"name":"PDA Journal of Pharmaceutical Science and Technology","volume":" ","pages":"274-284"},"PeriodicalIF":0.0,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144037956","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":"PDA Journal Editorial Board-An Update.","authors":"Mike Sadowski","doi":"10.5731/pdajpst.2025.001943","DOIUrl":"https://doi.org/10.5731/pdajpst.2025.001943","url":null,"abstract":"","PeriodicalId":19986,"journal":{"name":"PDA Journal of Pharmaceutical Science and Technology","volume":"79 3","pages":"250-251"},"PeriodicalIF":0.0,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144209122","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":"Analysis of Virus Clearance for Biotechnology Manufacturing Processes from Early to Late Phase Development.","authors":"Opeyemi O Ajayi, Jackie L Cullinan, Innara Basria, Madaisabel Fuentes-Arias, Ashley Osuna-Najarro, Sarah Johnson, Talia Faison, Scott Lute","doi":"10.5731/pdajpst.2025-000001.1","DOIUrl":"10.5731/pdajpst.2025-000001.1","url":null,"abstract":"<p><p>The risk for virus contamination in biotechnology products (e.g., monoclonal antibodies, fusion proteins, or antibody-drug conjugates) derived from mammalian cell lines is a safety concern that must be evaluated from the early stages of development. The regulatory requirement for virus clearance that assesses the capacity of purification processes to remove endogenous and adventitious viruses is aimed at mitigating viral safety risk. A virus clearance database, containing virus clearance study data from biological license applications and investigational new drug submissions, has been maintained by the Food and Drug Administration's Center for Drug Evaluation and Research for over 15 years. Herein, an update is provided with regard to the impacts of process changes on the virus clearance during the product development cycle of biotechnology drug products based on the investigational new drug submissions received between January 1986 through March 2024. The current data demonstrated continuous robust removal of retroviruses and parvoviruses by chemical inactivation and virus-retentive filtration unit operations, respectively. Additional virus removal was supported by inclusion of one or more chromatography processes unit operations. For these processes, interactive process parameter effects were investigated for impacts on the reported virus clearance. The data reported here demonstrated that process- and product- specific considerations needed to be evaluated on a case-by-case basis to achieve robust and effective virus clearance for mammalian-cell-derived biotechnology products.</p>","PeriodicalId":19986,"journal":{"name":"PDA Journal of Pharmaceutical Science and Technology","volume":" ","pages":"252-273"},"PeriodicalIF":0.0,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143987373","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":"Preservative Efficacy Testing of Refrigerated Pharmaceuticals: Choice of Challenging Isolate and Storage Temperature.","authors":"Seyed Sadeq Mousavi Ghahfarrokhi, Zeinab Zarei, Khadijeh Hamidian, Sepideh Nikrou, Mohammad-Reza Seidi, Hossein Jamalifar, Nasrin Samadi","doi":"10.5731/pdajpst.2024-003021.1","DOIUrl":"10.5731/pdajpst.2024-003021.1","url":null,"abstract":"<p><p>The antimicrobial effectiveness test assesses the performance of the preservatives and/or antimicrobial substances added to multiuse sterile or nonsterile dosage forms to protect these products from microbiological growth. In this study, insulin products underwent the European Pharmacopoeia and the United States Pharmacopeia antimicrobial preservative effectiveness tests at both room and refrigerated temperatures. Notably, a psychrotolerant strain, <i>Serratia marcescens</i>, originally isolated from a refrigerated pharmaceutical product, was included in the antimicrobial effectiveness testing. When evaluated against the compendial requirements, both neutral protamine Hagedorn and regular insulin stored at room temperature successfully met the European Pharmacopoeia-A criteria and the United States Pharmacopeia standards. However, although both formulations stored under refrigeration conformed to the United States Pharmacopeia criteria, they failed to satisfy the European Pharmacopoeia-A criteria at contact times of <7 days. The reductions in <i>Serratia marcescens</i> counts were the same at both incubation temperatures. This study indicated that for sterile multidose vials, performing the antimicrobial effectiveness test at both room and refrigerated temperatures might give a more accurate indication of antimicrobial preservative efficacy.</p>","PeriodicalId":19986,"journal":{"name":"PDA Journal of Pharmaceutical Science and Technology","volume":" ","pages":"285-294"},"PeriodicalIF":0.0,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144028173","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":"Retrospective Evaluation of Cycled Resin in Viral Clearance Studies-A Multiple Company Collaboration-Post ICH Q5A(R2) Review.","authors":"Jennifer Anderson, Chelsea Burgwin, Donna Hamilton","doi":"10.5731/pdajpst.2024-003024.1","DOIUrl":"10.5731/pdajpst.2024-003024.1","url":null,"abstract":"<p><p>In 2019, the <i>BioPhorum Development Group Viral Clearance Workstream</i> performed a collaborative retrospective analysis to evaluate packed bed chromatographic resin performance after repeated cycling for two commonly used chromatography steps in biopharmaceutical manufacturing: protein A and anion exchange. Key variables evaluated in the assessment included virus type, resin type, number of reuse cycles, and virus challenge. This paper has been amended to include additional commentary on the ICH Q5A revision adopted in November 2023. In this retrospective analysis of viral clearance data on naïve versus cycled resin, powered by the availability of decades' worth of accumulated industry data, clearance capability was not negatively impacted by resin cycling. This finding is consistent with publications showing that surrogates for viral clearance capabilities could be employed in lieu of testing of viral clearance of cycled resins for protein A and anion exchange chromatography. The rigorous analysis of the retrospective data supports the view that viral clearance studies for cycled protein A and anion exchange resins are not necessary, provided that appropriate cleaning methods are applied during repeated use of chromatography columns. In agreement with this paper, ICH Q5A(R2) acknowledges that used resin studies are not required for protein A. Used resin evaluation is still required for other chromatography steps; however, with appropriate justification, prior knowledge may be used in place of product-specific studies.</p>","PeriodicalId":19986,"journal":{"name":"PDA Journal of Pharmaceutical Science and Technology","volume":" ","pages":"320-336"},"PeriodicalIF":0.0,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144032813","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":"Settle plates with a diameter of 150 mm can be exposed to unidirectional airflow for up to 8 hours.","authors":"Martin Falke","doi":"10.5731/pdajpst.2024-003029.1","DOIUrl":"https://doi.org/10.5731/pdajpst.2024-003029.1","url":null,"abstract":"<p><p>Active and passive air monitoring is crucial for gaining knowledge about the microbial status of cleanroom environments for aseptic processing. Most agencies require active air monitoring of defined volumes in short time periods. However, active air monitoring methods may disrupt the unidirectional airflow of filtered air and are therefore difficult to use for continuous air monitoring. Hence, settle plates are additionally placed at areas of high risk during the whole filling process including set-up. While EU GMP Annex 1 9.30 defines a maximum duration of 4 hours for settle plates with a diameter of 90 mm and <USP 1116> defines a maximum of 4 to 5 hours respectively, there are no recommendations for settle plates with a diameter of 150 mm. Agencies expect validation studies including recovery rates as a basis to determine the exposure time. This study provides data showing that settle plates with a diameter of 150 mm can be placed under unidirectional airflow for up to 8 hours in a cleanroom with moderate humidity. No negative effect on the suitability of the media was observed. Moreover, it is shown that, settle plates with a diameter of 150 mm can be exposed to unidirectional airflow for up to 6 hours in a cleanroom with very low humidity as used for aseptic filling of lyophilized products. Increased exposure times of settle plates for up to 6 respectively 8 hours significantly reduce the exchange frequency of settle plates, which ultimately lowers the risk from microbial contamination during filling due to less interventions.</p>","PeriodicalId":19986,"journal":{"name":"PDA Journal of Pharmaceutical Science and Technology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144132759","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A biosafety toolbox for manufacturing with single-use systems.","authors":"Richard Denk, Reinhold Maeck, Dirk Motzkus, Carola Dreier, Bernhard Steidle, Andreas Seiffert, Stefan Woog, Harald Eriksson, Charlotte Hieke, Chris Williams, Susanne Konrad, Joachim Regel, Sven Verguts","doi":"10.5731/pdajpst.2025-000003.1","DOIUrl":"https://doi.org/10.5731/pdajpst.2025-000003.1","url":null,"abstract":"<p><p>As markets for recombinant biologicals constantly grow, risks related to the biohazardous materials used are not yet always understood and assessed systematically. Thus, there is a strong need to systematically assess technical solutions in GMP area and best practices for all steps in biotechnological production using biohazardous materials up to biological safety level 2. Especially Viral vectors, Virus based vaccines are more coming to market as novel therapies, asking for different safety requirements.As Single Use Solutions (SUS) are widely used in clinical- and production scale in Upstream and Downstream processing until Final fill operations, new practices must be developed with a different approach enabling production under BSL2.Production of biologics which are produced in BSL2 area regime using SU solutions must be reviewed under different aspects in terms of safety for the product + staff equally and probable contamination of the environment. SU Solutions for this new purpose must be differently handled with care from goods entry until final discard of products post usage. The production starting at fabricator of the SUS items itself might require modifications. The design of SUS items for the BSL2 purpose must be tested already in a different way in production, to fulfill the higher safety level regimes to protect the product and operators. In this paper we give examples for considerations how to unpack, store such SUS consumables and which conditions in the facility are favorable in combination with proper staff training Examples of suitable components and existing SUS equipment's for the Upstream- and Downstream processing of such products, to give operators, Suite- and plant managers, A+E with planers and people in regulatory departments the needed information, to enable the safe and regulatory aligned production of such biologic therapies.</p>","PeriodicalId":19986,"journal":{"name":"PDA Journal of Pharmaceutical Science and Technology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144132798","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}