PDA Journal of Pharmaceutical Science and Technology最新文献

{"title":"Per- and Polyfluoroalkyl Substances (PFAS) in Primary Packaging and the Proposed Ban in the European Union.","authors":"Taras T Bredel, John Adamsen, Torben Helmer","doi":"10.5731/pdajpst.2025.25203","DOIUrl":"https://doi.org/10.5731/pdajpst.2025.25203","url":null,"abstract":"<p><p>In February 2023 a restriction proposal to the European Chemicals Agency (ECHA) was submitted by five member countries of the European Union proposing a substantial restriction under the Registration, Evaluation, Authorization and Restriction of Chemical substances (REACH) regulation Annex XV for the use of all PFAS variants, thereby potentialy listing all PFASs as Substances of Very High Concern (SVHC).</p>","PeriodicalId":19986,"journal":{"name":"PDA Journal of Pharmaceutical Science and Technology","volume":"79 2","pages":"240-241"},"PeriodicalIF":0.0,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144079540","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":"Quantitative and Qualitative Evaluation of Microorganism Profile Identified in Bioburden Analysis in a Biopharmaceutical Facility in Brazil: Criteria for Classification and Management of Results.","authors":"Josiane Machado Vieira Mattoso, Luciana Veloso da Costa, Bruna de Almeida do Vale, Cristhiane Falavina Dos Reis, Joyce Modesto de Andrade, Lygia Maria Paulo da Silva Braga, Greice Maria Silva da Conceição, Paulo Borges Mathias Costa, Igor Barbosa da Silva, Letícia de Alencar Pereira Rodrigues, Jeancarlo Pereira Dos Anjos, Marcelo Luiz Lima Brandão","doi":"10.5731/pdajpst.2023.012883","DOIUrl":"10.5731/pdajpst.2023.012883","url":null,"abstract":"<p><p>Microbiological contamination may cause microbial proliferation and consequently additional problems for pharmaceutical companies through production stoppage, product contamination, investigations of process deviations, out-of-specification results, and product disposal. This is one of the major concerns of the regulatory health agencies. Microbiological load (bioburden) may represent a potential risk for patients if the sterilization process is not effective and/or due to the production of toxins. Although bioburden can be eliminated by terminal sterilization or filtration processes, it is important to monitor the amount and determine the identity and characteristics of the microorganisms present prior to final processing. The application of microorganism identification systems is crucial for identifying the type of contamination, which can be extremely useful for investigating. The aim of this study was to evaluate the profiles of microorganisms identified in bioburden assays from solutions, culture media, and products (SCP) from a pharmaceutical industry facility. From 2018-2020, a total of 1078 samples from 857 different lots of SCP were analyzed and the isolated microorganisms were identified. A prefiltering step was included after March 2020 in order to reduce the bioburden before sterilizing filtration. Criteria for the definition and management of the microorganisms identified were evaluated after an integrative bibliographic review, and three groups were proposed (critical, objectionable, and nonobjectionable microorganisms). For the samples that did not include prefiltering (n = 636), 227 (35.7%) presented microbial growth. For those that included prefiltering, before prefiltering (n = 221), 60.6% presented microbial growth, and after prefiltering, this value was reduced to 4.1%. Microbial growth recovered after prefiltration is likely to be attributed to contamination during sample collection or filtration. From the samples that presented microbial growth, 678 microorganisms were identified as bacteria and 59 as molds and yeasts. A total of 120 microorganisms (56 and 27 Gram-positive and Gram-negative bacteria, respectively, 31 yeasts, and 6 filamentous molds) could not be identified, and the remaining microorganisms were classified as objectionable (n = 507; 82.2%), nonobjectionable (n = 103; 16.7%), and critical (n = 7; 1.1%). Most of the bioburden species (>80.0%) were considered objectionable microorganisms. A process for classification and management of bioburden analysis results based on a literature review of pathogenic and physiological characteristics of the microorganisms was proposed.</p>","PeriodicalId":19986,"journal":{"name":"PDA Journal of Pharmaceutical Science and Technology","volume":" ","pages":"125-156"},"PeriodicalIF":0.0,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141470064","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":"https://doi.org/10.5731/pdajpst.2024-003023.1","url":null,"abstract":"<p><p>Post-approval changes (PACs) are integral to pharmaceutical product lifecycle 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 obtaining approval from NRAs, impacting global supply chains, and ultimately jeopardizing timely access of essential medical products to patients. In 2021, the WHO 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 of medical products to populations who need them. This approach was tested in a CMC 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 demonstrates that regulatory reliance is feasible. Of the 21 Regulatory 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 company responses amongst 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":""},"PeriodicalIF":0.0,"publicationDate":"2025-04-29","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":"https://doi.org/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 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 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 pre-determined force and holding the displacement constant for a desired timeframe. The Constant Force method monitors the displacement signal obtained from applying a predetermined force and holding the force constant for a desired timeframe. Supplementing experimental data generated for both methods with 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 supports the viability of using the constant force mechanical container closure integrity test method for improving the in-process CCI testing strategy for solution products.</p>","PeriodicalId":19986,"journal":{"name":"PDA Journal of Pharmaceutical Science and Technology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-04-29","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":"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":"https://doi.org/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 (NS) in prefilled syringes (PFS). Upon piercing through elastomeric (i.e., synthetic rubber) components, the physical interaction between the needle and 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 non-linear 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":""},"PeriodicalIF":0.0,"publicationDate":"2025-04-29","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":"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":"https://doi.org/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 application and investigational new drug submissions, has been maintained by the Food and Drug Administration's Center for Drug Evaluation and Research for over fifteen years. Herein, an update is provided with regard to 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":""},"PeriodicalIF":0.0,"publicationDate":"2025-04-29","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":"https://doi.org/10.5731/pdajpst.2024-003021.1","url":null,"abstract":"<p><p>The antimicrobial effectiveness testing assesses the performance of preservatives and/or antimicrobial substances added to multi-use sterile or non-sterile dosage forms, protecting 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 NPH and REG 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 less than 7 days. The reductions in <i>Serratia marcescens</i> counts were the same at both incubation temperatures. This study indicated that for sterile multi-dose vials, performing the antimicrobial effectiveness testing at both room and refrigerated temperatures might give more accurate indication of antimicrobial preservative efficacy.</p>","PeriodicalId":19986,"journal":{"name":"PDA Journal of Pharmaceutical Science and Technology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-04-29","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":"https://doi.org/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":""},"PeriodicalIF":0.0,"publicationDate":"2025-04-29","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":"A proof-of-concept study on a universal standard kit to evaluate the risks of inspectors for their foundational ability of visual inspection of injectable drug products.","authors":"Hirohito Katayama, Manabu Tsuda, Yukari Koga, Nobuaki Habasaki, Kosuke Taniyama, Yuichi Minato, Akihiro Oda, Kouichi Nagata, Takashi Amagasa, Kimitaka Misawa","doi":"10.5731/pdajpst.2023.012911","DOIUrl":"https://doi.org/10.5731/pdajpst.2023.012911","url":null,"abstract":"<p><p>Visual inspectors' ability to detect foreign matter in injections must be qualified for each product type or bracketing group, as stated in the United States Pharmacopeia <1790>. The common defect criterion is ″visible″ However, this qualitative lower rejection limit is based on the premise that the nature of human inspection at one site is globally comparable to that at all other sites. If not, the ″visible″ foreign matter can vary among inspector groups for each product, leading to quality differences between sites. Inspectors are trained and qualified using ″visible″ foreign matter samples from their site; therefore, inspectors' ability to detect foreign matter can differ due to different standards. Japanese pharmaceutical companies import injections and perform secondary visual inspections because variations in ″visible″ ability arise due to individual differences among regions. Currently, there is no universal method for comparing ″visible″ rejection zones among manufacturing sites for different products because product-specific standard samples for qualifications cannot be universalized. Therefore, instead of comparing the product-specific ″visible″ standard sample, this study proposes a novel universal particle standard challenge kit to compare sites' or inspectors' inner ″visible″ detection ability. Our results suggest that the proposed kit could evaluate the comparability of ″visible″ at each site and for each inspector but not on sites' ″visible″ standard samples. The primary challenge in implementing a universal standard lies in the inherent bias of inspectors already acclimated to specific products. This study found that an inspectors' foundational ability can be evaluated by canceling the bias via rapid and effective training in cases of simple standard samples. Our results suggest that using a universal standard kit to assess an inspector's fundamental ability to detect ″visible″ foreign matter is feasible. The study does not aim to replace the inspectors' product qualifications but to compare their inner ability for risk assessment.</p>","PeriodicalId":19986,"journal":{"name":"PDA Journal of Pharmaceutical Science and Technology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143710749","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":"Phase-Incremental Decision Trees for Multi-Phase Feature Selection and Interaction in Biologics Manufacturing.","authors":"Nolan Gunter, Yang Tang, Jonathan Ritscher, Yiming Peng","doi":"10.5731/pdajpst.2024-003020","DOIUrl":"https://doi.org/10.5731/pdajpst.2024-003020","url":null,"abstract":"<p><p>Data from cell culture processes contain myriad parameters arriving sequentially in phases which may hold vital information for optimizing process runs and ameliorating manufacturing yield. This study analyzed temporal process data from 249 cell culture production batches of an active pharmaceutical ingredient at Roche's Location A manufacturing facility. The titer manufactured is utilized for Roche's Product X, a prescription drug that can treat adults with cancer. We aim to optimize the upstream production phase titer in Chinese hamster ovary cell manufacturing by identifying the most influential features. A phase-incremental (PI) decision tree method is proposed for feature selection and interaction exploration, being model and loss function agnostic while promoting early feature importance for prediction and process control. In this case study, the method is applied to Ensemble of Gradient Boosting Machines, using adjusted R-squared as the penalized loss function. The result leads to better process understanding and enables earlier control in the manufacturing.</p>","PeriodicalId":19986,"journal":{"name":"PDA Journal of Pharmaceutical Science and Technology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143710836","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}