PDA Journal of Pharmaceutical Science and Technology最新文献

{"title":"Establishment of a Single Temperature Incubation Approach for Environmental Monitoring Samples with Focus on Mold Recoveries.","authors":"Alana Poloni, Janete GonÇalves, MÓnica Pereira, Alexander Stoll","doi":"10.5731/pdajpst.2022.012769","DOIUrl":"10.5731/pdajpst.2022.012769","url":null,"abstract":"<p><p>A robust environmental monitoring program is essential to properly estimate and identify microorganisms in cleanrooms, ensuring that microbial contamination remains acceptably low and that a good state of control is maintained in the manufacturing areas. The incubation conditions are important to support optimal microbial recoveries, considering that there is no single culture medium, temperature, and incubation time that can recover all microorganisms. In particular, molds are quite sensitive microorganisms, and some species may have very specific nutritional and environmental needs. In this study, a two-phase approach was used to identify a single incubation-temperature approach that could recover most of the cleanroom microbial flora, with a focus on molds. Phase 1 included a growth promotion study performed in the laboratory using pharmacopeial and in-house strains, comparing different media (Sabouraud Dextrose Agar [SDA] and Tryptone Soy Agar [TSA]) at single or dual incubation-temperature approaches for 5 or 6 days. Phase 2 was based on an in-situ study in which sampling was performed in different areas of a pharmaceutical facility and the recoveries at different incubation conditions were compared. In addition, extension studies of Phase 1 and Phase 2 were performed to get a better understanding of growth requirements for in-house molds. The results showed that an incubation on TSA at 25°C-30°C for 3-4 days was able to recover most tested microorganisms in Phase 1 and a large variety of microorganisms in Phase 2, indicating that the single incubation-temperature is an optimal approach for the recovery of microorganisms in cleanrooms. Exceptions were noted for one strain of the species <i>Cutibacterium acnes,</i> a microaerophilic bacterium for which anaerobiosis and higher temperatures were needed, and two mold strains (<i>Sistotrema brinkmannii</i> and <i>Stereum hirsutum</i>), indicating that those molds required a specific media (SDA) for their proliferation. The results showed that TSA incubated at the single or dual incubation-temperature approach cannot compensate for the absence of SDA for some environmental molds that may be atypical in cleanrooms. Therefore, in addition to TSA, certain monitoring with SDA at, for example, cleanroom entrance points may be beneficial to recover molds with very specific nutritional requirements.</p>","PeriodicalId":19986,"journal":{"name":"PDA Journal of Pharmaceutical Science and Technology","volume":" ","pages":"312-330"},"PeriodicalIF":0.0,"publicationDate":"2024-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41237604","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 Method to Investigate Sterilization Processes and the Bacterial Inactivation Resolved in Time and Space.","authors":"Manuel Feurhuber, Thomas Taupitz, Frank Mueller, Carsten Frank, Christoph Hochenauer, Valentin Schwarz","doi":"10.5731/pdajpst.2022.012771","DOIUrl":"10.5731/pdajpst.2022.012771","url":null,"abstract":"<p><p>In this study, a computational fluid dynamics (CFD) model was developed to predict all relevant phenomena occurring during a moist heat sterilization process at a high level of temporal and spatial resolution. The developed CFD model was used to simulate the distribution of, for example, pressure, temperature, and residual air within a large-scale industrial steam autoclave (multiphase flow models), which was not published until now. Moreover, the thermodynamic behavior and distribution of fluids and temperatures inside the sterilization load were simulated and were verified with measurements. Based on the obtained sterilization temperature profiles in connection with the sterilization environment (e.g., non-condensable gases, natural convection), bacterial inactivation could be simulated. A complete moist heat sterilization process was simulated, including all relevant phenomena inside an autoclave chamber and a Peritoneal Dialysis Bag System (PDBS), which represents a complex sterilization item. To verify the simulation results, simulated pressures and temperatures were compared with measurement data for both the autoclave chamber and the PDBS. The results show that the simulated and measured values were in excellent accordance. By using the novel CFD model, the distribution of steam and residual air inside the autoclave chamber, as well as the natural convection inside the sterilization load, could be precisely predicted. To predict the inactivation of <i>Geobacillus stearothermophilus</i> inside different moist heat environments, the CFD model was extended with bacterial inactivation kinetics based on measurement data. The simulation results clearly indicate that our developed CFD model can be used to predict the inactivation kinetics of bacteria, depending on the sterilization temperature profile of the sterilization process as well as the moist heat sterilization environment, and to resolve the kinetics in time and space. Therefore, the developed CFD model represents a powerful tool that might be used in the future to predict, for example, \"worst case\" locations for any given autoclave and sterilization load or any other relevant process parameter, enabling the operator to develop an effective sterilization process.</p>","PeriodicalId":19986,"journal":{"name":"PDA Journal of Pharmaceutical Science and Technology","volume":" ","pages":"331-347"},"PeriodicalIF":0.0,"publicationDate":"2024-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136398655","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":"Artificial Intelligence: Boon or Curse?","authors":"","doi":"10.5731/pdajpst.2024.001834","DOIUrl":"10.5731/pdajpst.2024.001834","url":null,"abstract":"","PeriodicalId":19986,"journal":{"name":"PDA Journal of Pharmaceutical Science and Technology","volume":"78 3","pages":"212-213"},"PeriodicalIF":0.0,"publicationDate":"2024-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141470065","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":"Accurate or Protective: What Is the Goal of Non-Targeted Extractables and Leachables Quantitation and Identification?","authors":"Dennis Jenke","doi":"10.5731/pdajpst.2023.012868","DOIUrl":"10.5731/pdajpst.2023.012868","url":null,"abstract":"<p><p>Leachables are quantified and identified to enable their quantitative toxicological safety risk assessment (qTSRA). The leachable's reported concentration and identity must meet certain quality expectations to be suitable for qTSRA. In this Correspondence, the author considers accuracy and protectiveness as competing key quality attributes and suggests that protectiveness is the proper quality attribute for qTSRA, as qTSRA is based on the foundation that a leachable's potential adverse effect on patient health and safety must not be underestimated. Considering this conclusion, means of making concentration estimates and proposed identities protective are discussed.</p>","PeriodicalId":19986,"journal":{"name":"PDA Journal of Pharmaceutical Science and Technology","volume":" ","pages":"358-366"},"PeriodicalIF":0.0,"publicationDate":"2024-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136398656","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":"Comparison of Binary Alcohol/Water Solvent Systems to Blood for Extractions of Blood-Contacting Medical Devices","authors":"M. Jordi, Taryn Meade, Kevin Rowland, Chi-hu Ho, Jordan Tocher, Weixi Liu","doi":"10.5731/pdajpst.2023.012892","DOIUrl":"https://doi.org/10.5731/pdajpst.2023.012892","url":null,"abstract":"","PeriodicalId":19986,"journal":{"name":"PDA Journal of Pharmaceutical Science and Technology","volume":"32 12","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140657571","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":"Applying Knowledge to Manage Risk - A Case Study in Application of the Risk Knowledge Infinity (RKI) Cycle","authors":"Peer Schmidt, M. Lipa, Jace Fogle, Owen Baker, Timothy Pawlak, Sean McEwen, Kevin O'Donnell","doi":"10.5731/pdajpst.2023.012931","DOIUrl":"https://doi.org/10.5731/pdajpst.2023.012931","url":null,"abstract":"","PeriodicalId":19986,"journal":{"name":"PDA Journal of Pharmaceutical Science and Technology","volume":"56 15","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140656714","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":"Proceedings of the 2023 Viral Clearance Symposium: 2023 VCS Summary, Pending Questions, and Next Steps.","authors":"David Roush, Glen Bolton","doi":"10.5731/pdajpst.2024.002240","DOIUrl":"https://doi.org/10.5731/pdajpst.2024.002240","url":null,"abstract":"<p><p>The 2023 Viral Clearance Symposium (VCS) was hosted by Takeda on 24 and 25 May 2023 in Vienna, Austria. The present conference extended the structure of the previous biennial symposia held between 2009 and 2019. As recapitulated in the introductory session, the genesis of the VCS, as described in the Proceedings of the 2009 VCS was \"the worldwide regulatory and industry recognition that challenges, gaps, and opportunities exist, that it formally addressed could benefit the field as whole.\" This report provides a synopsis of the progress achieved at the conference resulting from detailed technical discussions and the pending questions that still require attention to address. The 2023 VCS was composed of nine individual sessions of short presentations followed by in-depth panel discussions from the presenters. Sessions included Regulatory Updates (with a focus on ICH Q5A(R2) efforts), including a summary of lessons learned from the 2019 VCS, and progress on these key areas mapped into 2023 VCS topics: Viral Clearance Strategy and Case Studies, New Modalities in Chromatography and Adsorptive Filters, Continuous Processing, Viral Clearance Strategy and Process Understanding, Virus Inactivation, Upstream and Downstream Virus Retentive Filtration and Cell Banks, and Advanced Technologies (advanced therapy medicinal products, next-generation sequencing).</p>","PeriodicalId":19986,"journal":{"name":"PDA Journal of Pharmaceutical Science and Technology","volume":"78 2","pages":"141-143"},"PeriodicalIF":0.0,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140868933","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":"Proceedings of the 2023 Viral Clearance Symposium, Session 3: 2023 VCS New Modalities in Chromatography and Adsorptive Filters.","authors":"David Roush, Glen Bolton","doi":"10.5731/pdajpst.2024.002243","DOIUrl":"https://doi.org/10.5731/pdajpst.2024.002243","url":null,"abstract":"<p><p>The session provided an update on the application and mechanistic understanding of intensified unit operations (e.g., mixed mode depth filters, mixed mode AEX) since the last conference in 2019. One of the key gaps identified in the 2019 Viral Clearance Symposium session on the topic was for more investigation required to achieve a clear understanding of the molecular mechanisms of virus removal and the relevance of different moleculés interactions including resin, virus, and product. Further investigation into worst-case conditions for these unit operations is also warranted. One of the key outcomes from that 2019 discussion was also that multimodal anion exchangers can have robust and effective virus removal, depending on process and impurities-an observation that was recapitulated with more specific case studies and evidenced by broader application of these chromatographic resins in late-stage regulatory filings.</p>","PeriodicalId":19986,"journal":{"name":"PDA Journal of Pharmaceutical Science and Technology","volume":"78 2","pages":"157-168"},"PeriodicalIF":0.0,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140850843","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":"Proceedings of the 2023 Viral Clearance Symposium, Session 2: Viral Clearance Strategy and Case Studies.","authors":"Frank Kohne, Astrid Schwantes","doi":"10.5731/pdajpst.2024.002242","DOIUrl":"https://doi.org/10.5731/pdajpst.2024.002242","url":null,"abstract":"<p><p>This session deals with the rational design of viral clearance studies for biopharmaceuticals including recombinant proteins such as monoclonal antibodies and, as new in scope of the symposium, also viral clearance for adeno-associated viral (AAV) vectors. For recombinant proteins, large datasets were accumulated over the last decades and are intended to be used for accelerated product process development and streamlining of viral clearance studies. How to utilize prior knowledge in viral clearance validation and how it can be used in a risk assessment tool to decide whether additional virus clearance studies are necessary during product development is being addressed by three of the presentations of this session. This also includes an a priori intended design and generation of validation data for a new kind of detergent such as CG-110, to build up a platform dataset to be used as prior knowledge in future marketing application. Another presentation investigates the virus removal mechanism of a newly developed hydrophobic interaction chromatography (HIC) resin and demonstrates for highly hydrophobic antibodies appropriate reduction for a retrovirus and impurities in a defined process range in contrast to the moderate to poor virus reduction of recent HIC resins. The last two presentations deal with virus clearance approaches for AAV, which will become mandatory with approval of the ICH Q5A revision. Appropriate virus removal and virus inactivation procedures can be implemented into the manufacturing processes of AAV vectors including viral filtration, viral inactivation (e.g., heat inactivation), affinity chromatography, and anion-exchange chromatography with which it seems possible to achieve a good clearance for helper and also adventitious viruses. The heat treatment step can be even a robust step for adenovirus helper inactivation for AAV products when product characteristics and process conditions are understood.</p>","PeriodicalId":19986,"journal":{"name":"PDA Journal of Pharmaceutical Science and Technology","volume":"78 2","pages":"147-156"},"PeriodicalIF":0.0,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140868609","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":"Proceedings of the 2023 Viral Clearance Symposium, Session 5: Viral Clearance Strategy and Process Understanding.","authors":"Kurt Brorson, Sean O'Donnell","doi":"10.5731/pdajpst.2024.002245","DOIUrl":"https://doi.org/10.5731/pdajpst.2024.002245","url":null,"abstract":"<p><p>Session 5 of the 2023 Viral Clearance Symposium reviewed the strategy and process understanding of viral clearance testing. Topics included learnings from the past, leveraging surrogate-based methodologies, cleaning agents that inactivate enveloped baculoviruses, segregation, and retrovirus-like particles both in continuous process and in-use as spiking viruses. Overall, there were discussions over a wide array of viral clearance determinants.</p>","PeriodicalId":19986,"journal":{"name":"PDA Journal of Pharmaceutical Science and Technology","volume":"78 2","pages":"176-186"},"PeriodicalIF":0.0,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140867357","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}