Manufacturing technologies for the production of clinical grade viral vectors have been significantly improved in recent years. This is of utmost importance for gene therapy approaches used in the treatment of inherited or acquired diseases. This article briefly describes the general principles for the production of viral vectors. The specific sections are dedicated to more detailed descriptions of the production of adenoviral, AAV, γ-retroviral and lentiviral vectors. A subsequent article (the second part) will then deal with downstream processing (purification) of viral vectors.
{"title":"Manufacturing of viral vectors for gene therapy: part I. Upstream processing","authors":"O. Merten, M. Schweizer, P. Chahal, A. Kamen","doi":"10.4155/PBP.14.16","DOIUrl":"https://doi.org/10.4155/PBP.14.16","url":null,"abstract":"Manufacturing technologies for the production of clinical grade viral vectors have been significantly improved in recent years. This is of utmost importance for gene therapy approaches used in the treatment of inherited or acquired diseases. This article briefly describes the general principles for the production of viral vectors. The specific sections are dedicated to more detailed descriptions of the production of adenoviral, AAV, γ-retroviral and lentiviral vectors. A subsequent article (the second part) will then deal with downstream processing (purification) of viral vectors.","PeriodicalId":90285,"journal":{"name":"Pharmaceutical bioprocessing","volume":"2 1","pages":"183-203"},"PeriodicalIF":0.0,"publicationDate":"2014-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4155/PBP.14.16","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70346981","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":"Recombinant protein and mAb biopharmaceuticals to become a commodity","authors":"E. V. Corven","doi":"10.4155/PBP.14.11","DOIUrl":"https://doi.org/10.4155/PBP.14.11","url":null,"abstract":"","PeriodicalId":90285,"journal":{"name":"Pharmaceutical bioprocessing","volume":"2 1","pages":"107-109"},"PeriodicalIF":0.0,"publicationDate":"2014-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4155/PBP.14.11","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70346757","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}
Christian Lüder, P. Lindner, David Bulnes‐Abundis, Shaobin Lu, Tim H. Lücking, D. Solle, T. Scheper
Background: The use of modern sensors for online monitoring has become increasingly important in biotechnology. For bioprocess analysis the chemical and physical environment as well as the biological component itself must be monitored in detail and in real-time. Results: Modern non-invasive optical sensors allow reliable predictions of the current process status just in time. Two sensors, one for the biologic and one for monitoring the chemical system of a CHO cell cultivation process, are presented. With an in situ microscope, cell count and morphology are monitored, to assess the efficiency of the cell growth up to a cell concentration of 1.4·107 cells/ml. An infrared sensor was used to analyze glucose concentration profiles. Both sensors can be used as in situ non-invasive sensors. Conclusion: With both sensors, reliable online monitoring of CHO cell cultivation process is feasible that react immediately to changes in process conditions. Higher product quality and more efficient processes can be realized.
{"title":"In situ microscopy and MIR-spectroscopy as non-invasive optical sensors for cell cultivation process monitoring","authors":"Christian Lüder, P. Lindner, David Bulnes‐Abundis, Shaobin Lu, Tim H. Lücking, D. Solle, T. Scheper","doi":"10.4155/PBP.14.13","DOIUrl":"https://doi.org/10.4155/PBP.14.13","url":null,"abstract":"Background: The use of modern sensors for online monitoring has become increasingly important in biotechnology. For bioprocess analysis the chemical and physical environment as well as the biological component itself must be monitored in detail and in real-time. Results: Modern non-invasive optical sensors allow reliable predictions of the current process status just in time. Two sensors, one for the biologic and one for monitoring the chemical system of a CHO cell cultivation process, are presented. With an in situ microscope, cell count and morphology are monitored, to assess the efficiency of the cell growth up to a cell concentration of 1.4·107 cells/ml. An infrared sensor was used to analyze glucose concentration profiles. Both sensors can be used as in situ non-invasive sensors. Conclusion: With both sensors, reliable online monitoring of CHO cell cultivation process is feasible that react immediately to changes in process conditions. Higher product quality and more efficient processes can be realized.","PeriodicalId":90285,"journal":{"name":"Pharmaceutical bioprocessing","volume":"2 1","pages":"157-166"},"PeriodicalIF":0.0,"publicationDate":"2014-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4155/PBP.14.13","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70346954","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}
Present research has found that antifoams can have a broad range of effects upon bioprocesses, both on the culture environment and upon the cells themselves.
目前的研究发现，抗泡沫剂可以对生物过程产生广泛的影响，无论是对培养环境还是对细胞本身。
{"title":"Antifoams: the overlooked additive?","authors":"S. Routledge, D. Poyner, R. Bill","doi":"10.4155/PBP.14.5","DOIUrl":"https://doi.org/10.4155/PBP.14.5","url":null,"abstract":"Present research has found that antifoams can have a broad range of effects upon bioprocesses, both on the culture environment and upon the cells themselves.","PeriodicalId":90285,"journal":{"name":"Pharmaceutical bioprocessing","volume":"2 1","pages":"103-106"},"PeriodicalIF":0.0,"publicationDate":"2014-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4155/PBP.14.5","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70348596","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}
The role of microbiologists in pharmaceutical development and manufacturing has become more visible in recent years due to the QbD and risk-based approaches promoted by regulatory authorities and industry [1]. Microbiology, microbiological control and contamination control are indispensable in the manufacture of sterile and nonsterile products as well as biologic drug substances, as evidenced by multiple conference presentations and publications. Terms such as objectionable microorganisms, organisms of concern, alert and action limits, environmental monitoring and sterility are dominating our daily work. Lack of sterility assurance is the number one reason for recalls of sterile drug products, and presence of objectionable organisms is the number one reason for recalls of nonsterile products [2,3]. While no one disputes the role of microbiologists in the design and development of pharmaceutical manufacturing processes, microbiologists still appear ‘confined’ in the laboratory of the manufacturing facility long after a process has been established and approved. They are not visible as equal partners in the development process along with chemists and pharmacists. However, microbiology issues frequently arise and critical decisions must be made. The science of microbiology and its applications have a large impact on microbiological and contamination-control strategies for robust and consistent processes with infrequent failures and contaminations. End-product testing is no longer considered acceptable for assuring product quality. Back to the basics When expectations and practices seem to drift away from science and reach scientifically unjustifiable terrain, we need to go ‘back to the basics’ and the science of applied microbiology. This is even more necessary when regulatory expectations impose scientifically insupportable requirements and expectations. Training and mentoring microbiologists in the basic principles of microbiology is critical. Microorganisms do not visit facilities out of nowhere; there is a source associated with their origin and introduction into a facility and manufacturing process. Once introduced, favorable conditions are required for a microorganism’s growth. Such conditions must be evaluated to understand whether this microorganism could represent a hazard to the product and patient. Microbiological control centers primarily on preventing the introduction of microorganisms into a manufacturing process. If introduction cannot prevented, then control is achieved by destruction, removal, inhibition of microorganisms, or a combination of these approaches. Drug product sterility is based on destruction or removal of microorganisms and is indicated for products that bypass the human body’s natural defenses (e.g., parenteral administration). In the case of nonsterile products, APIs, excipients and biologic drug substances, small amounts of microorganisms are acceptable provided that they do not replicate in the final material duri
{"title":"The role of microbiology in the design and development of pharmaceutical manufacturing processes","authors":"A. Lolas","doi":"10.4155/PBP.14.6","DOIUrl":"https://doi.org/10.4155/PBP.14.6","url":null,"abstract":"The role of microbiologists in pharmaceutical development and manufacturing has become more visible in recent years due to the QbD and risk-based approaches promoted by regulatory authorities and industry [1]. Microbiology, microbiological control and contamination control are indispensable in the manufacture of sterile and nonsterile products as well as biologic drug substances, as evidenced by multiple conference presentations and publications. Terms such as objectionable microorganisms, organisms of concern, alert and action limits, environmental monitoring and sterility are dominating our daily work. Lack of sterility assurance is the number one reason for recalls of sterile drug products, and presence of objectionable organisms is the number one reason for recalls of nonsterile products [2,3]. While no one disputes the role of microbiologists in the design and development of pharmaceutical manufacturing processes, microbiologists still appear ‘confined’ in the laboratory of the manufacturing facility long after a process has been established and approved. They are not visible as equal partners in the development process along with chemists and pharmacists. However, microbiology issues frequently arise and critical decisions must be made. The science of microbiology and its applications have a large impact on microbiological and contamination-control strategies for robust and consistent processes with infrequent failures and contaminations. End-product testing is no longer considered acceptable for assuring product quality. Back to the basics When expectations and practices seem to drift away from science and reach scientifically unjustifiable terrain, we need to go ‘back to the basics’ and the science of applied microbiology. This is even more necessary when regulatory expectations impose scientifically insupportable requirements and expectations. Training and mentoring microbiologists in the basic principles of microbiology is critical. Microorganisms do not visit facilities out of nowhere; there is a source associated with their origin and introduction into a facility and manufacturing process. Once introduced, favorable conditions are required for a microorganism’s growth. Such conditions must be evaluated to understand whether this microorganism could represent a hazard to the product and patient. Microbiological control centers primarily on preventing the introduction of microorganisms into a manufacturing process. If introduction cannot prevented, then control is achieved by destruction, removal, inhibition of microorganisms, or a combination of these approaches. Drug product sterility is based on destruction or removal of microorganisms and is indicated for products that bypass the human body’s natural defenses (e.g., parenteral administration). In the case of nonsterile products, APIs, excipients and biologic drug substances, small amounts of microorganisms are acceptable provided that they do not replicate in the final material duri","PeriodicalId":90285,"journal":{"name":"Pharmaceutical bioprocessing","volume":"2 1","pages":"125-128"},"PeriodicalIF":0.0,"publicationDate":"2014-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4155/PBP.14.6","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70348577","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}
In the past few decades there has been an increasing demand of biopharmaceutical proteins in the market. Several types of cell factories are applied to produce different pharmaceutical proteins. However, manufacturers prefer to use a few favorable biological platforms to undertake the production tasks with low cost, high productivity and proper post-translational modifications. The yeast Saccharomyces cerevisiae is one of these preferred cell factories as it meets many of the requirements. There are several reports on improvement of recombinant protein production by S. cerevisiae through rational engineering of different stages of the protein secretion pathway. However, recent developments of new technologies like systems biology and synthetic biology open new doors to design S. cerevisiae as an ideal production platform.
{"title":"Biopharmaceutical protein production by Saccharomyces cerevisiae: current state and future prospects","authors":"Mingtao Huang, Jichen Bao, J. Nielsen","doi":"10.4155/PBP.14.8","DOIUrl":"https://doi.org/10.4155/PBP.14.8","url":null,"abstract":"In the past few decades there has been an increasing demand of biopharmaceutical proteins in the market. Several types of cell factories are applied to produce different pharmaceutical proteins. However, manufacturers prefer to use a few favorable biological platforms to undertake the production tasks with low cost, high productivity and proper post-translational modifications. The yeast Saccharomyces cerevisiae is one of these preferred cell factories as it meets many of the requirements. There are several reports on improvement of recombinant protein production by S. cerevisiae through rational engineering of different stages of the protein secretion pathway. However, recent developments of new technologies like systems biology and synthetic biology open new doors to design S. cerevisiae as an ideal production platform.","PeriodicalId":90285,"journal":{"name":"Pharmaceutical bioprocessing","volume":"64 1","pages":"167-182"},"PeriodicalIF":0.0,"publicationDate":"2014-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4155/PBP.14.8","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70349506","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}
Background: Analytical method qualification consists of a simplified evaluation of a subset of validation characteristics with a goal to demonstrate that an analytical method is scientifically sound and suitable for its intended use. In contrast to validation, analytical method qualification is performed without predefined acceptability criteria. Qualification may be performed as a prerequisite to method validation, or when an assay for product knowledge has not yet been established as a test for a critical product quality attribute. Methodology The focus of this study was the qualification of a differential scanning calorimetry method that is used to examine thermal stability and tertiary structure of protein vaccine antigens and monoclonal antibody products. The analytical parameter evaluated was precision, through assessment of the characteristics of repeatability and intermediate precision. Conclusion: The results demonstrated that the assay met the desired performance characteristics, and is suitable...
{"title":"Qualification of a differential scanning calorimetry method for biophysical characterization of monoclonal antibodies and protein vaccine antigens","authors":"M. Kirkitadze, Jian Hu, Mei Tang, B. Carpick","doi":"10.4155/PBP.14.27","DOIUrl":"https://doi.org/10.4155/PBP.14.27","url":null,"abstract":"Background: Analytical method qualification consists of a simplified evaluation of a subset of validation characteristics with a goal to demonstrate that an analytical method is scientifically sound and suitable for its intended use. In contrast to validation, analytical method qualification is performed without predefined acceptability criteria. Qualification may be performed as a prerequisite to method validation, or when an assay for product knowledge has not yet been established as a test for a critical product quality attribute. Methodology The focus of this study was the qualification of a differential scanning calorimetry method that is used to examine thermal stability and tertiary structure of protein vaccine antigens and monoclonal antibody products. The analytical parameter evaluated was precision, through assessment of the characteristics of repeatability and intermediate precision. Conclusion: The results demonstrated that the assay met the desired performance characteristics, and is suitable...","PeriodicalId":90285,"journal":{"name":"Pharmaceutical bioprocessing","volume":"2 1","pages":"491-498"},"PeriodicalIF":0.0,"publicationDate":"2014-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4155/PBP.14.27","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70347787","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}
Approximately 50 years after the good manufacturing practice (GMP) regulations were first issued, regulatory inspections of firms operating under GMP are still uncovering cases of non-compliance with the rules concerning written operating procedures and the need to follow them. These rules are fundamental to GMP and are simple to understand. Future changes to GMP will emphasize risk management and the need to have an effective quality culture in the firm. SOPs will still form an essential part of the quality system. This article examines the principal problem areas in standard operating procedure management and provides recommendations for correcting them.
{"title":"Standard operating procedures revisited: a 2014 perspective","authors":"A. Kanarek","doi":"10.4155/pbp.14.1","DOIUrl":"https://doi.org/10.4155/pbp.14.1","url":null,"abstract":"Approximately 50 years after the good manufacturing practice (GMP) regulations were first issued, regulatory inspections of firms operating under GMP are still uncovering cases of non-compliance with the rules concerning written operating procedures and the need to follow them. These rules are fundamental to GMP and are simple to understand. Future changes to GMP will emphasize risk management and the need to have an effective quality culture in the firm. SOPs will still form an essential part of the quality system. This article examines the principal problem areas in standard operating procedure management and provides recommendations for correcting them.","PeriodicalId":90285,"journal":{"name":"Pharmaceutical bioprocessing","volume":"2 1","pages":"41-47"},"PeriodicalIF":0.0,"publicationDate":"2014-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4155/pbp.14.1","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70346596","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}
Tim Sandle is Head of Microbiology at Bio Products Laboratory (Hertfordshire, UK). In addition, he is a visiting tutor with the School of Pharmacy and Pharmaceutical Sciences, University of Manchester (Manchester, UK) where he teaches the University’s pharmaceutical microbiology MSc course. Sandle serves on several national and international committees including the microbiology society Pharmig (Hertfordshire, UK). Sandle has written almost three hundred book chapters, peer-reviewed papers and technical articles relating to microbiology, as well as being the author or co-editor of eight books. Sandle runs a microbiology discussion site, Pharmaceutical Microbiology. Sandle spoke to Pharmaceutical Bioprocessing for the first in a series of interviews on pharmaceutical microbiology. Interview conducted by Jessica Thorne, Assistant Commissioning Editor.
Tim Sandle是生物制品实验室(英国赫特福德郡)微生物学负责人。此外，他还是曼彻斯特大学(Manchester, UK)药学院的客座导师，教授该大学的药物微生物学硕士课程。桑德尔服务于几个国家和国际委员会，包括微生物学会药学(赫特福德郡，英国)。Sandle撰写了近300篇与微生物学相关的书籍章节、同行评议的论文和技术文章，同时还是八本书的作者或共同编辑。桑德尔经营着一个微生物学讨论网站——药物微生物学。桑德尔在一系列关于药物微生物学的采访中首次向制药生物加工公司发表了讲话。采访由杰西卡·索恩，助理委托编辑。
{"title":"Interview: Pharmaceutical microbiology","authors":"Tim Sandle","doi":"10.4155/PBP.13.64","DOIUrl":"https://doi.org/10.4155/PBP.13.64","url":null,"abstract":"Tim Sandle is Head of Microbiology at Bio Products Laboratory (Hertfordshire, UK). In addition, he is a visiting tutor with the School of Pharmacy and Pharmaceutical Sciences, University of Manchester (Manchester, UK) where he teaches the University’s pharmaceutical microbiology MSc course. Sandle serves on several national and international committees including the microbiology society Pharmig (Hertfordshire, UK). Sandle has written almost three hundred book chapters, peer-reviewed papers and technical articles relating to microbiology, as well as being the author or co-editor of eight books. Sandle runs a microbiology discussion site, Pharmaceutical Microbiology. Sandle spoke to Pharmaceutical Bioprocessing for the first in a series of interviews on pharmaceutical microbiology. Interview conducted by Jessica Thorne, Assistant Commissioning Editor.","PeriodicalId":90285,"journal":{"name":"Pharmaceutical bioprocessing","volume":"2 1","pages":"17-21"},"PeriodicalIF":0.0,"publicationDate":"2014-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4155/PBP.13.64","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70346081","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":"Are automated disposable small-scale reactors set to dominate the future of pharmaceutical bioprocess development?","authors":"D. Pollard","doi":"10.4155/PBP.13.62","DOIUrl":"https://doi.org/10.4155/PBP.13.62","url":null,"abstract":"","PeriodicalId":90285,"journal":{"name":"Pharmaceutical bioprocessing","volume":"2 1","pages":"9-12"},"PeriodicalIF":0.0,"publicationDate":"2014-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4155/PBP.13.62","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70346432","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}
京公网安备 11010802042870号
京ICP备2023020795号-1
扫码关注我们
求助内容：
应助结果提醒方式：