Approximately 30% of all currently licensed, recombinantly expressed biotherapeutic products are produced in Escherichia coli, among which a significant proportion are exported to the periplasm by the general Secretory ‘Sec’ pathway. However, this pathway cannot handle many target proteins and the Tat pathway is emerging as a powerful alternative means of export. The Tat system exports fully folded proteins, moreover it preferentially exports correctly folded proteins and has been shown to export a range of biotherapeutics. This review will discuss our current understanding of the Tat pathway and its potential application for the industrial-scale production of biotherapeutics.
{"title":"The Tat pathway as a biotechnological tool for the expression and export of heterologous proteins in Escherichia coli","authors":"Kelly L. Walker, Alexander S. Jones, C. Robinson","doi":"10.4155/PBP.15.21","DOIUrl":"https://doi.org/10.4155/PBP.15.21","url":null,"abstract":"Approximately 30% of all currently licensed, recombinantly expressed biotherapeutic products are produced in Escherichia coli, among which a significant proportion are exported to the periplasm by the general Secretory ‘Sec’ pathway. However, this pathway cannot handle many target proteins and the Tat pathway is emerging as a powerful alternative means of export. The Tat system exports fully folded proteins, moreover it preferentially exports correctly folded proteins and has been shown to export a range of biotherapeutics. This review will discuss our current understanding of the Tat pathway and its potential application for the industrial-scale production of biotherapeutics.","PeriodicalId":90285,"journal":{"name":"Pharmaceutical bioprocessing","volume":"3 1","pages":"387-396"},"PeriodicalIF":0.0,"publicationDate":"2015-10-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4155/PBP.15.21","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70352122","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}
Conventional pharmaceutical manufacturing, whose outdated processes are fraught with significant operational and logistical issues, fails to address the ‘on demand’ needs of today’s military and civilian patient populations. Recent advances within the DARPA Battlefield Medicine program suggest that innovative and flexible platforms for producing pharmaceuticals and biologics can be developed that minimize waste, improve capacity to handle wide-ranging operational conditions, and manufacture multiple types of therapeutics – all within short time frames. A distributed ‘on demand’ therapeutics manufacturing system obviates the need for individual drug stockpiling, cold storage requirements and complex logistics, while enabling costeffective production of small quantities of medications, such as orphan drugs, and permits the flexibility and responsiveness required in manufacturing to adequately meet the general supply chain needs.
{"title":"Battlefield medicine: disrupting (bio) pharmaceutical production","authors":"Eugene J. Choi, J. Lewin, Geoffrey S. F. Ling","doi":"10.4155/PBP.15.17","DOIUrl":"https://doi.org/10.4155/PBP.15.17","url":null,"abstract":"Conventional pharmaceutical manufacturing, whose outdated processes are fraught with significant operational and logistical issues, fails to address the ‘on demand’ needs of today’s military and civilian patient populations. Recent advances within the DARPA Battlefield Medicine program suggest that innovative and flexible platforms for producing pharmaceuticals and biologics can be developed that minimize waste, improve capacity to handle wide-ranging operational conditions, and manufacture multiple types of therapeutics – all within short time frames. A distributed ‘on demand’ therapeutics manufacturing system obviates the need for individual drug stockpiling, cold storage requirements and complex logistics, while enabling costeffective production of small quantities of medications, such as orphan drugs, and permits the flexibility and responsiveness required in manufacturing to adequately meet the general supply chain needs.","PeriodicalId":90285,"journal":{"name":"Pharmaceutical bioprocessing","volume":"3 1","pages":"361-369"},"PeriodicalIF":0.0,"publicationDate":"2015-10-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4155/PBP.15.17","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70352294","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}
Monoclonal antibodies are currently the most successful class of therapeutic agents. However, the conventional immunoglobulin (Ig) format is not always optimally suited to meet clinical demands. First, immunological effector functions mediated by the Fc region can evoke undesired side effects. Second, poor tissue penetration due to the large molecular size hampers successful treatment of solid tumors. Also, the long circulation in blood resulting from both the large size and FcRn-mediated endosomal recycling is unfavorable both for therapies that require flexible adjustment of dosing and for in vivo imaging applications. Finally, due to their complex biomolecular architecture, including four polypeptide chains with around 1500 amino acids and at least two glycosylation sites, the production of full size antibodies is costly and requires mammalian expression systems. As a consequence, during the last two decades more than 50 alternative types of binding proteins have been proposed with the intention to overcome some of the inherent limitations of antibodies. However, only a minority of these ‘alternative scaffolds’ have reached the clinic so far, which can be seen as the ultimate success in pharmaceutical biotechnology. According to recent reviews, ten drug candidates based on seven different protein scaffolds have been tested in clinical trials while one biological received market approval (the engineered Kunitz domain/protease inhibitor ecallantide) [1,2]. At present, the biopharmaceutical development is dominated by the following protein scaffolds: • Affibodies based on the Z-domain of Staphylococcal protein A [3];
{"title":"‘Engineered protein scaffolds: have they lived up to expectations?’","authors":"A. Skerra, S. Schmidt","doi":"10.4155/PBP.15.20","DOIUrl":"https://doi.org/10.4155/PBP.15.20","url":null,"abstract":"Monoclonal antibodies are currently the most successful class of therapeutic agents. However, the conventional immunoglobulin (Ig) format is not always optimally suited to meet clinical demands. First, immunological effector functions mediated by the Fc region can evoke undesired side effects. Second, poor tissue penetration due to the large molecular size hampers successful treatment of solid tumors. Also, the long circulation in blood resulting from both the large size and FcRn-mediated endosomal recycling is unfavorable both for therapies that require flexible adjustment of dosing and for in vivo imaging applications. Finally, due to their complex biomolecular architecture, including four polypeptide chains with around 1500 amino acids and at least two glycosylation sites, the production of full size antibodies is costly and requires mammalian expression systems. As a consequence, during the last two decades more than 50 alternative types of binding proteins have been proposed with the intention to overcome some of the inherent limitations of antibodies. However, only a minority of these ‘alternative scaffolds’ have reached the clinic so far, which can be seen as the ultimate success in pharmaceutical biotechnology. According to recent reviews, ten drug candidates based on seven different protein scaffolds have been tested in clinical trials while one biological received market approval (the engineered Kunitz domain/protease inhibitor ecallantide) [1,2]. At present, the biopharmaceutical development is dominated by the following protein scaffolds: • Affibodies based on the Z-domain of Staphylococcal protein A [3];","PeriodicalId":90285,"journal":{"name":"Pharmaceutical bioprocessing","volume":"3 1","pages":"383-386"},"PeriodicalIF":0.0,"publicationDate":"2015-10-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4155/PBP.15.20","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70352425","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}
P. Desai, Griet Van Vaerenbergh, J. Holman, C. Liew, P. Heng
The highly conservative pharmaceutical industry is now approaching an era of renewal, transforming from batch manufacturing to continuous manufacturing, to convert seamlessly in fast continuous sequence, raw materials into high-quality final products [1,2]. This transformation is significant, to meet demands on solid dosage forms manufacture through cost savings by simplifying processes, reduced space and energy footprints, reduce product failures and yet, provide even better quality products for patients [3,4]. Full automation allows for consistent product quality produced under 24 h production capabilities [5]. However, high initial investment cost, vagueness on the long-term capability of the manufacturing system and the uncertainty of regulatory requirements for continuously manufactured products are some initial hurdles creating reluctance to adopt this highly required transformation. Currently, the most common pharmaceutical solid dosage form, tablets are manufactured by batch manufacturing. First, active pharmaceutical ingredients (APIs) are manufactured in upstream steps which mainly involve chemical synthesis, reaction engineering, crystallization, separation and purification. Almost 70% of the upstream reaction steps are in batch mode [6]. Many companies are now trying to change these batch reactions with flow reactions to generate API with minimal losses. In the next stage, isolated APIs are further treated by different downstream steps to formulate the dosage form, tablets. In a perfect future world, fully end to end continuous manufacturing, which is also coined as homogeneous processing, will take root and terms such as upstream and downstream processing may not exist anymore [7]. Homogeneous processing requires the incorporation or development of new technologies. However, before the dream of homogeneous processing becomes a reality, a transformative transitional phase, in which heterogeneous continuous processing involving the streamlining of upstream processing and downstream processing as continuous phases, has to be initiated. GEA Pharma Systems is a leading group of companies involved in developing these continuous processing systems, particularly for downstream processing and some of their systems are discussed here to provide recent updates in this emerging area. The downstream steps for batch manufacturing of tablets involve one of the three common methods: wet granulation, dry granulation and direct compression [7]. Blending and milling are also the parts of the downstream processes and are carried out as according to the requirements. In this aspect, recently developed downstream processing methods such as melt extrusion, thin film casting and electrospinning can be considered as continuous processing with less powder handling [8]. Major limitation to prepare tablets via batch manufacturing is the requirement of very good flowing feed materials. Wet granulation is the popular method to convert free particles into aggregat
{"title":"Continuous manufacturing: the future in pharmaceutical solid dosage form manufacturing","authors":"P. Desai, Griet Van Vaerenbergh, J. Holman, C. Liew, P. Heng","doi":"10.4155/PBP.15.19","DOIUrl":"https://doi.org/10.4155/PBP.15.19","url":null,"abstract":"The highly conservative pharmaceutical industry is now approaching an era of renewal, transforming from batch manufacturing to continuous manufacturing, to convert seamlessly in fast continuous sequence, raw materials into high-quality final products [1,2]. This transformation is significant, to meet demands on solid dosage forms manufacture through cost savings by simplifying processes, reduced space and energy footprints, reduce product failures and yet, provide even better quality products for patients [3,4]. Full automation allows for consistent product quality produced under 24 h production capabilities [5]. However, high initial investment cost, vagueness on the long-term capability of the manufacturing system and the uncertainty of regulatory requirements for continuously manufactured products are some initial hurdles creating reluctance to adopt this highly required transformation. Currently, the most common pharmaceutical solid dosage form, tablets are manufactured by batch manufacturing. First, active pharmaceutical ingredients (APIs) are manufactured in upstream steps which mainly involve chemical synthesis, reaction engineering, crystallization, separation and purification. Almost 70% of the upstream reaction steps are in batch mode [6]. Many companies are now trying to change these batch reactions with flow reactions to generate API with minimal losses. In the next stage, isolated APIs are further treated by different downstream steps to formulate the dosage form, tablets. In a perfect future world, fully end to end continuous manufacturing, which is also coined as homogeneous processing, will take root and terms such as upstream and downstream processing may not exist anymore [7]. Homogeneous processing requires the incorporation or development of new technologies. However, before the dream of homogeneous processing becomes a reality, a transformative transitional phase, in which heterogeneous continuous processing involving the streamlining of upstream processing and downstream processing as continuous phases, has to be initiated. GEA Pharma Systems is a leading group of companies involved in developing these continuous processing systems, particularly for downstream processing and some of their systems are discussed here to provide recent updates in this emerging area. The downstream steps for batch manufacturing of tablets involve one of the three common methods: wet granulation, dry granulation and direct compression [7]. Blending and milling are also the parts of the downstream processes and are carried out as according to the requirements. In this aspect, recently developed downstream processing methods such as melt extrusion, thin film casting and electrospinning can be considered as continuous processing with less powder handling [8]. Major limitation to prepare tablets via batch manufacturing is the requirement of very good flowing feed materials. Wet granulation is the popular method to convert free particles into aggregat","PeriodicalId":90285,"journal":{"name":"Pharmaceutical bioprocessing","volume":"7 1","pages":"357-360"},"PeriodicalIF":0.0,"publicationDate":"2015-10-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4155/PBP.15.19","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70352356","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}
Intense efforts in bioprocessing development have been made to improve the production of Chinese Hamster Ovary-based biopharmaceuticals. However, lacking an efficient host cell has hampered therapeutic protein production. This article reviews means by which biopharmaceutical production can be improved via cell engineering. We first discuss the traditional and recently developed strategies to improve protein productivity through regulating cell growth and facilitating cell line construction, increase protein quality by upregulating the post-translational modifications and enhance production stability through targeting integration and chromatin remodeling. New cell engineering technologies, such as miRNA, CRISPR/Cas and synthetic promoter, are then reviewed. The application of advanced ‘omics to reinforce a fundamental understanding of cellular metabolism and physiology is also described. Finally, rational cell engineering facilitated with ‘omics technologies is presented.
{"title":"Achievements and perspectives in Chinese hamster ovary host cell engineering","authors":"N. Xu, Chao Ma, W. Sun, Youling Wu, X. M. Liu","doi":"10.4155/PBP.15.16","DOIUrl":"https://doi.org/10.4155/PBP.15.16","url":null,"abstract":"Intense efforts in bioprocessing development have been made to improve the production of Chinese Hamster Ovary-based biopharmaceuticals. However, lacking an efficient host cell has hampered therapeutic protein production. This article reviews means by which biopharmaceutical production can be improved via cell engineering. We first discuss the traditional and recently developed strategies to improve protein productivity through regulating cell growth and facilitating cell line construction, increase protein quality by upregulating the post-translational modifications and enhance production stability through targeting integration and chromatin remodeling. New cell engineering technologies, such as miRNA, CRISPR/Cas and synthetic promoter, are then reviewed. The application of advanced ‘omics to reinforce a fundamental understanding of cellular metabolism and physiology is also described. Finally, rational cell engineering facilitated with ‘omics technologies is presented.","PeriodicalId":90285,"journal":{"name":"Pharmaceutical bioprocessing","volume":"3 1","pages":"285-292"},"PeriodicalIF":0.0,"publicationDate":"2015-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4155/PBP.15.16","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70352283","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}
Y. Lyubarskaya, Kazumi Kobayashi, Patrick G. Swann
Development and implementation of process analytical technology and real-time release testing (here defined as advanced process controls) requires an approach to product development that emphasizes product and process understanding and process control, based on sound science and quality risk management (i.e., quality by design). Mathematical models can enhance the scientific understanding of a process and can also be explored for their predictive capability. Utilizing advanced process controls and mathematical models for biopharmaceutical products can be challenging given product/process complexity. Recent publications and preliminary work from our group are reviewed to show how the analytical capabilities of mass spectrometry can be leveraged to address these challenges.
{"title":"Application of mass spectrometry to facilitate advanced process controls of biopharmaceutical manufacture","authors":"Y. Lyubarskaya, Kazumi Kobayashi, Patrick G. Swann","doi":"10.4155/PBP.15.10","DOIUrl":"https://doi.org/10.4155/PBP.15.10","url":null,"abstract":"Development and implementation of process analytical technology and real-time release testing (here defined as advanced process controls) requires an approach to product development that emphasizes product and process understanding and process control, based on sound science and quality risk management (i.e., quality by design). Mathematical models can enhance the scientific understanding of a process and can also be explored for their predictive capability. Utilizing advanced process controls and mathematical models for biopharmaceutical products can be challenging given product/process complexity. Recent publications and preliminary work from our group are reviewed to show how the analytical capabilities of mass spectrometry can be leveraged to address these challenges.","PeriodicalId":90285,"journal":{"name":"Pharmaceutical bioprocessing","volume":"3 1","pages":"313-321"},"PeriodicalIF":0.0,"publicationDate":"2015-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4155/PBP.15.10","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70350383","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 growth in stratified medicine and the economic pressures to reduce capital investment, cost of development and cost of goods are forcing a change in how biopharmaceutical manufacturing plants are designed, built and operated. It is likely that future manufacturing facilities will be built on the principle of flexibility and make even greater use of single use technology, continuous manufacturing and alternative expression systems. Large scale production will in many cases be achieved by the ‘scale out’ of multiple smaller facilities rather than the ‘scale up’ to large capacity plants. Some of the core technology required to achieve this vision is already available though further development is required in many areas.
{"title":"Biopharmaceutical factory of the future","authors":"R. Alldread, Jonathan Robinson","doi":"10.4155/PBP.15.11","DOIUrl":"https://doi.org/10.4155/PBP.15.11","url":null,"abstract":"The growth in stratified medicine and the economic pressures to reduce capital investment, cost of development and cost of goods are forcing a change in how biopharmaceutical manufacturing plants are designed, built and operated. It is likely that future manufacturing facilities will be built on the principle of flexibility and make even greater use of single use technology, continuous manufacturing and alternative expression systems. Large scale production will in many cases be achieved by the ‘scale out’ of multiple smaller facilities rather than the ‘scale up’ to large capacity plants. Some of the core technology required to achieve this vision is already available though further development is required in many areas.","PeriodicalId":90285,"journal":{"name":"Pharmaceutical bioprocessing","volume":"3 1","pages":"293-304"},"PeriodicalIF":0.0,"publicationDate":"2015-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4155/PBP.15.11","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70351425","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 recent years, it has become increasingly clear that glycosylation of key pathogen glycoprotein antigens can significantly affect antigenic properties. For example, pathogens, such as human immunodeficiency virus and influenza, can develop a ‘glycoshield’ over key antigens as they passage through host populations. In addition to shielding of antigenic sites key changes in glycosylation have been shown to modify host innate immune responses and both of these phenomena can potentially impact vaccine performance. A better understanding of glycosylation properties of vaccine antigens may better guide development of these products and management of their production processes. Due to the complexity of oligosaccharides, the analysis of these glycosylation states has been difficult and time consuming. With the advent of cutting edge mass spectrometry based techniques many of the barriers to glycan and glycoprotein analysis have been lowered. Combined with traditional techniques such as high field NMR, GC/MS, CE...
{"title":"Monitoring vaccine protein glycosylation: analytics and recent developments","authors":"J. Cipollo","doi":"10.4155/PBP.15.13","DOIUrl":"https://doi.org/10.4155/PBP.15.13","url":null,"abstract":"In recent years, it has become increasingly clear that glycosylation of key pathogen glycoprotein antigens can significantly affect antigenic properties. For example, pathogens, such as human immunodeficiency virus and influenza, can develop a ‘glycoshield’ over key antigens as they passage through host populations. In addition to shielding of antigenic sites key changes in glycosylation have been shown to modify host innate immune responses and both of these phenomena can potentially impact vaccine performance. A better understanding of glycosylation properties of vaccine antigens may better guide development of these products and management of their production processes. Due to the complexity of oligosaccharides, the analysis of these glycosylation states has been difficult and time consuming. With the advent of cutting edge mass spectrometry based techniques many of the barriers to glycan and glycoprotein analysis have been lowered. Combined with traditional techniques such as high field NMR, GC/MS, CE...","PeriodicalId":90285,"journal":{"name":"Pharmaceutical bioprocessing","volume":"59 1","pages":"323-340"},"PeriodicalIF":0.0,"publicationDate":"2015-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4155/PBP.15.13","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70352148","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 presence of aggregates in biopharmaceutical products has long been considered a concern to product safety and product quality. Specifications for acceptable levels of aggregates for a novel therapeutic protein are typically set based on manufacturing capability and clinical qualification. While these parameters are still relevant for biosimilars, additional strategy must also be applied to ensure that the aggregate profile is acceptable in comparison to the originator product, both in terms of number and types of aggregates present. This article discusses regulatory strategy that may be employed in the development of analytical methods and specifications for a biosimilar product.
{"title":"Regulatory strategy for the development of analytical methods for the routine determination of aggregate profiles for a biosimilar product","authors":"C. Vessely","doi":"10.4155/PBP.15.15","DOIUrl":"https://doi.org/10.4155/PBP.15.15","url":null,"abstract":"The presence of aggregates in biopharmaceutical products has long been considered a concern to product safety and product quality. Specifications for acceptable levels of aggregates for a novel therapeutic protein are typically set based on manufacturing capability and clinical qualification. While these parameters are still relevant for biosimilars, additional strategy must also be applied to ensure that the aggregate profile is acceptable in comparison to the originator product, both in terms of number and types of aggregates present. This article discusses regulatory strategy that may be employed in the development of analytical methods and specifications for a biosimilar product.","PeriodicalId":90285,"journal":{"name":"Pharmaceutical bioprocessing","volume":"3 1","pages":"305-312"},"PeriodicalIF":0.0,"publicationDate":"2015-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4155/PBP.15.15","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70352271","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":"Limitless starting materials for large-scale manufacture of MSCs – what does the future hold?","authors":"K. Kelly","doi":"10.4155/PBP.15.14","DOIUrl":"https://doi.org/10.4155/PBP.15.14","url":null,"abstract":"","PeriodicalId":90285,"journal":{"name":"Pharmaceutical bioprocessing","volume":"3 1","pages":"281-283"},"PeriodicalIF":0.0,"publicationDate":"2015-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4155/PBP.15.14","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70352225","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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