The contribution of regulatory agencies to the continuous improvement of the equipment maintenance processes management Pharmaceutical companies have followed the internal development process that regulatory agencies like US FDA, EMA or ANVISA, for example, have passed through on the last years. If, some time ago, their auditors were focusing more on product quality itself when auditing production sites, nowadays they want to see the quality mindset embedded in other areas of support like maintenance, logistics or human resources. Also, their professionals currently have a skills set broader than they used to have in terms of out-of-the-pharmaceutical-box knowledge. It means that many of them know what to look for when auditing, for example, the quality of a maintenance plan, the skills matrix of a technician or even the root cause analysis of an equipment breakdown. In this aspect, it is reasonable to say that the audits of these regulatory agencies are currently much more constructive because they focus not on finding issues, but on how the issues are systematically treated in order to avoid reoccurrence. Then, when auditing maintenance departments, it’s not a surprise that they want to see how the maintenance processes are managed, what established flows for normal activities are in place and what treatment is given when deviations on these flows occur. This ‘push’ is highly contributing to the development of a quality mindset inside maintenance departments and forcing pharmaceutical companies to see maintenance not only as the needed evil, but also as a strong contributor to make sure that the products will have the minimum quality standards. The challenge is to deliver the activities needed by the maintenance processes in a way that the overall production costs will not be ‘overloaded’ by the quality needs.
{"title":"The impact of a company's equipment maintenance strategy on its competitiveness","authors":"Frederico F Giunchetti","doi":"10.4155/pbp.14.52","DOIUrl":"https://doi.org/10.4155/pbp.14.52","url":null,"abstract":"The contribution of regulatory agencies to the continuous improvement of the equipment maintenance processes management Pharmaceutical companies have followed the internal development process that regulatory agencies like US FDA, EMA or ANVISA, for example, have passed through on the last years. If, some time ago, their auditors were focusing more on product quality itself when auditing production sites, nowadays they want to see the quality mindset embedded in other areas of support like maintenance, logistics or human resources. Also, their professionals currently have a skills set broader than they used to have in terms of out-of-the-pharmaceutical-box knowledge. It means that many of them know what to look for when auditing, for example, the quality of a maintenance plan, the skills matrix of a technician or even the root cause analysis of an equipment breakdown. In this aspect, it is reasonable to say that the audits of these regulatory agencies are currently much more constructive because they focus not on finding issues, but on how the issues are systematically treated in order to avoid reoccurrence. Then, when auditing maintenance departments, it’s not a surprise that they want to see how the maintenance processes are managed, what established flows for normal activities are in place and what treatment is given when deviations on these flows occur. This ‘push’ is highly contributing to the development of a quality mindset inside maintenance departments and forcing pharmaceutical companies to see maintenance not only as the needed evil, but also as a strong contributor to make sure that the products will have the minimum quality standards. The challenge is to deliver the activities needed by the maintenance processes in a way that the overall production costs will not be ‘overloaded’ by the quality needs.","PeriodicalId":90285,"journal":{"name":"Pharmaceutical bioprocessing","volume":"3 1","pages":"9-11"},"PeriodicalIF":0.0,"publicationDate":"2015-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4155/pbp.14.52","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70348869","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}
Pluripotent stem cell-related products represent a new product category from the pharmaceutical and biotechnology industry. The increased demand in disease research, drug screening and toxicity testing motivates the activities for large-scale production of stem cells or their derivatives through scale out and scale up approaches. This article highlights recent advances and the challenges in scale out and scale up of pluripotent stem cell derived products. While most current processes use scale out approaches, emerging technologies are being explored to fulfill the potential of scale up culture systems with the emphasis on the design of bioinspired process for large-scale biomanufacturing of stem cells.
{"title":"Toward biomanufacturing of pluripotent stem cell derived products: scale out and scale up","authors":"Yuanwei Yan, Liqing Song, Yan Li","doi":"10.4155/PBP.14.59","DOIUrl":"https://doi.org/10.4155/PBP.14.59","url":null,"abstract":"Pluripotent stem cell-related products represent a new product category from the pharmaceutical and biotechnology industry. The increased demand in disease research, drug screening and toxicity testing motivates the activities for large-scale production of stem cells or their derivatives through scale out and scale up approaches. This article highlights recent advances and the challenges in scale out and scale up of pluripotent stem cell derived products. While most current processes use scale out approaches, emerging technologies are being explored to fulfill the potential of scale up culture systems with the emphasis on the design of bioinspired process for large-scale biomanufacturing of stem cells.","PeriodicalId":90285,"journal":{"name":"Pharmaceutical bioprocessing","volume":"3 1","pages":"25-33"},"PeriodicalIF":0.0,"publicationDate":"2015-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4155/PBP.14.59","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70348970","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}
M. Leiss, Monika M. Meier, Oxana Pester, M. Aschner, F. Wedekind, M. Wiedmann, Harald Wegele
Aim: Host cell proteins represent a major process-related impurity in recombinant biotherapeutics. Present work reports about a fully automated platform based on a cobas instrument (Roche Diagnostic GmbH, Mannheim, Germany) allowing high-throughput determination of host cell proteins. Materials & methods: The instrument combines automated sample preparation with electrochemiluminescence-based detection technology, facilitating highly sensitive and accurate detection. Results: Our data shows that the assay performs readily comparable to conventional ELISAs, but outperforms in speed, sample throughput and by its superior linear range. Comparison of ELISA and electrochemiluminescence immunoassay validation results from more than ten independent validations of clinical product testing methods supports our comparability claim. Conclusion: The electrochemiluminescence immunoassay represents a milestone for bioprocess impurity testing and abolishes the sample throughput limitations posed by conventional ELISA.
{"title":"Getting CHO host cell protein analysis up to speed","authors":"M. Leiss, Monika M. Meier, Oxana Pester, M. Aschner, F. Wedekind, M. Wiedmann, Harald Wegele","doi":"10.4155/PBP.14.55","DOIUrl":"https://doi.org/10.4155/PBP.14.55","url":null,"abstract":"Aim: Host cell proteins represent a major process-related impurity in recombinant biotherapeutics. Present work reports about a fully automated platform based on a cobas instrument (Roche Diagnostic GmbH, Mannheim, Germany) allowing high-throughput determination of host cell proteins. Materials & methods: The instrument combines automated sample preparation with electrochemiluminescence-based detection technology, facilitating highly sensitive and accurate detection. Results: Our data shows that the assay performs readily comparable to conventional ELISAs, but outperforms in speed, sample throughput and by its superior linear range. Comparison of ELISA and electrochemiluminescence immunoassay validation results from more than ten independent validations of clinical product testing methods supports our comparability claim. Conclusion: The electrochemiluminescence immunoassay represents a milestone for bioprocess impurity testing and abolishes the sample throughput limitations posed by conventional ELISA.","PeriodicalId":90285,"journal":{"name":"Pharmaceutical bioprocessing","volume":"3 1","pages":"13-23"},"PeriodicalIF":0.0,"publicationDate":"2015-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4155/PBP.14.55","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70348735","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":"Productivity: a minor consideration when looking at mammalian cell culture performance from the systems perspective","authors":"Sohye Kang, P. Bondarenko, R. Deshpande","doi":"10.4155/PBP.14.56","DOIUrl":"https://doi.org/10.4155/PBP.14.56","url":null,"abstract":"","PeriodicalId":90285,"journal":{"name":"Pharmaceutical bioprocessing","volume":"3 1","pages":"5-8"},"PeriodicalIF":0.0,"publicationDate":"2015-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4155/PBP.14.56","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70348800","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":"What can cell culture flocculation offer for antibody purification processes","authors":"Y. Kang, D. Ludwig, P. Balderes","doi":"10.4155/PBP.14.33","DOIUrl":"https://doi.org/10.4155/PBP.14.33","url":null,"abstract":"","PeriodicalId":90285,"journal":{"name":"Pharmaceutical bioprocessing","volume":"2 1","pages":"483-485"},"PeriodicalIF":0.0,"publicationDate":"2014-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4155/PBP.14.33","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70347762","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}
Critical to the biopharmaceutical industrial objectives are robust, reproducible processes which result in consistent product quality and yields. These parameters support the product safety and efficacy as well as control over the process and supply chain. To have a consistent cell culture process, process inputs must be reliable. Historically cell culture media have been a source of variability through the inclusion of complex components such as hydrolysates and sera. Industry has shifted to chemically defined basal and feed media and seen reduced variability but chemically defined media have not eliminated process variability. This review will consequently focus on media variability, the subsequent outputs of lactate and ammonia production and product quality, and the possible routes to eliminate process inconsistency.
{"title":"Identifying and eliminating cell culture process variability","authors":"Alan Gilbert, Yao-ming Huang, T. Ryll","doi":"10.4155/PBP.14.35","DOIUrl":"https://doi.org/10.4155/PBP.14.35","url":null,"abstract":"Critical to the biopharmaceutical industrial objectives are robust, reproducible processes which result in consistent product quality and yields. These parameters support the product safety and efficacy as well as control over the process and supply chain. To have a consistent cell culture process, process inputs must be reliable. Historically cell culture media have been a source of variability through the inclusion of complex components such as hydrolysates and sera. Industry has shifted to chemically defined basal and feed media and seen reduced variability but chemically defined media have not eliminated process variability. This review will consequently focus on media variability, the subsequent outputs of lactate and ammonia production and product quality, and the possible routes to eliminate process inconsistency.","PeriodicalId":90285,"journal":{"name":"Pharmaceutical bioprocessing","volume":"2 1","pages":"519-534"},"PeriodicalIF":0.0,"publicationDate":"2014-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4155/PBP.14.35","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70347853","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":"Electrical stimuli in stem cell production and differentiation: an important factor?","authors":"M. Prat, D. Colangelo","doi":"10.4155/PBP.14.31","DOIUrl":"https://doi.org/10.4155/PBP.14.31","url":null,"abstract":"","PeriodicalId":90285,"journal":{"name":"Pharmaceutical bioprocessing","volume":"2 1","pages":"487-489"},"PeriodicalIF":0.0,"publicationDate":"2014-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4155/PBP.14.31","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70347659","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}
Plant cell culture is emerging as an alternative bioproduction system for recombinant pharmaceuticals. Growing plant cells in vitro under controlled environmental conditions allows for precise control over cell growth and protein production, batch-to-batch product consistency and a production process aligned with current good manufacturing practices. With the recent US FDA approval and commercialization of the world's first plant cell-based recombinant pharmaceutical for human use, β-glucocerebrosidase for treatment of Gaucher's disease, a new era has come in which plant cell culture shows high potential to displace some established platform technologies in niche markets. This review updates the progress in plant cell culture processing technology, highlights recent commercial successes and discusses the challenges that must be overcome to make this platform commercially viable.
{"title":"On the way to commercializing plant cell culture platform for biopharmaceuticals: present status and prospect.","authors":"Jianfeng Xu, Ningning Zhang","doi":"10.4155/pbp.14.32","DOIUrl":"https://doi.org/10.4155/pbp.14.32","url":null,"abstract":"<p><p>Plant cell culture is emerging as an alternative bioproduction system for recombinant pharmaceuticals. Growing plant cells <i>in vitro</i> under controlled environmental conditions allows for precise control over cell growth and protein production, batch-to-batch product consistency and a production process aligned with current good manufacturing practices. With the recent US FDA approval and commercialization of the world's first plant cell-based recombinant pharmaceutical for human use, β-glucocerebrosidase for treatment of Gaucher's disease, a new era has come in which plant cell culture shows high potential to displace some established platform technologies in niche markets. This review updates the progress in plant cell culture processing technology, highlights recent commercial successes and discusses the challenges that must be overcome to make this platform commercially viable.</p>","PeriodicalId":90285,"journal":{"name":"Pharmaceutical bioprocessing","volume":"2 6","pages":"499-518"},"PeriodicalIF":0.0,"publicationDate":"2014-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4155/pbp.14.32","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33327877","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Zhiwei Song Author for correspondence: Bioprocessing Technology Institute, Agency for Science, Technology & Research (A*STAR), 20 Biopolis Way, #06–01 Centros, Singapore 138668, Singapore Tel.: +65 64078844 Fax: +65 64789561 song_zhiwei@bti.a-star.edu.sg “Chinese hamster ovary-gmt4 cells represent an attractive cell line to produce highly sialylated recombinant therapeutics.” Pharmaceutical Editorial
{"title":"Improving sialylation of recombinant biologics for enhanced therapeutic efficacy","authors":"Kah Fai Chan, John S. Y. Goh, Zhiwei Song","doi":"10.4155/PBP.14.44","DOIUrl":"https://doi.org/10.4155/PBP.14.44","url":null,"abstract":"Zhiwei Song Author for correspondence: Bioprocessing Technology Institute, Agency for Science, Technology & Research (A*STAR), 20 Biopolis Way, #06–01 Centros, Singapore 138668, Singapore Tel.: +65 64078844 Fax: +65 64789561 song_zhiwei@bti.a-star.edu.sg “Chinese hamster ovary-gmt4 cells represent an attractive cell line to produce highly sialylated recombinant therapeutics.” Pharmaceutical Editorial","PeriodicalId":90285,"journal":{"name":"Pharmaceutical bioprocessing","volume":"2 1","pages":"363-366"},"PeriodicalIF":0.0,"publicationDate":"2014-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4155/PBP.14.44","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70348129","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}
Optimizing productivity from recombinant Chinese hamster ovary cells requires understanding of the transcriptional and translational regulatory processes. Several ‘omics approaches have been utilized to characterize these processes. Still, many questions remain unanswered as to the mechanisms underlying transgene expression. As a result, bioprocess development still remains highly variable, and the cell selection process must be repeated for every new product synthesized. It has become clear that epigenetic processes play a role in recombinant protein expression and that gaining a better understanding of these processes will aid in process development and cell-line selection. In this perspective, we highlight our current knowledge of the influence of various epigenetic factors that control recombinant protein expression.
{"title":"Role of epigenetics in expression of recombinant proteins from mammalian cells","authors":"Hussain Dahodwala, S. Sharfstein","doi":"10.4155/PBP.14.47","DOIUrl":"https://doi.org/10.4155/PBP.14.47","url":null,"abstract":"Optimizing productivity from recombinant Chinese hamster ovary cells requires understanding of the transcriptional and translational regulatory processes. Several ‘omics approaches have been utilized to characterize these processes. Still, many questions remain unanswered as to the mechanisms underlying transgene expression. As a result, bioprocess development still remains highly variable, and the cell selection process must be repeated for every new product synthesized. It has become clear that epigenetic processes play a role in recombinant protein expression and that gaining a better understanding of these processes will aid in process development and cell-line selection. In this perspective, we highlight our current knowledge of the influence of various epigenetic factors that control recombinant protein expression.","PeriodicalId":90285,"journal":{"name":"Pharmaceutical bioprocessing","volume":"2 1","pages":"403-419"},"PeriodicalIF":0.0,"publicationDate":"2014-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4155/PBP.14.47","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70348351","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}
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