Innovation in biomanufacturing: the only way forward

Innovations in the biomanufacturing industry are predominantly incremental in nature, but there are occasional major technological shifts that occur as existing technologies reach their limits and as additional constraints are imposed by market forces or regulatory bodies. These disruptive innovations tend to have a seismic effect, forcing companies to adopt novel strategies and business models in order to remain competitive. In this article, we discuss how technological innovation can address some of the current challenges in biopharmaceutical manufacturing by anticipating shifts in market dynamics and cost structures. We consider bioprocessing standards, unit operations, best practices, enabling technologies and look at potential entry points for innovation where technologies are likely to evolve incrementally and where more disruptive, radical changes may flourish, including quality by design and process analytical technology. We conclude that the biomanufacturing industry can only thrive in the changi...

[1]  Duncan Low,et al.  Future of antibody purification. , 2007, Journal of chromatography. B, Analytical technologies in the biomedical and life sciences.

[2]  S. Milstein,et al.  Evaluation of exogenous siRNA addition as a metabolic engineering tool for modifying biopharmaceuticals , 2013, Biotechnology progress.

[3]  Anurag S Rathore,et al.  Follow-on protein products: scientific issues, developments and challenges. , 2009, Trends in biotechnology.

[4]  B. Mattiasson,et al.  Macroporous monolithic gels, cryogels, with immobilized phages from phage-display library as a new platform for fast development of affinity adsorbent capable of target capture from crude feeds. , 2007, Journal of biotechnology.

[5]  P. Gagnon Technology trends in antibody purification. , 2012, Journal of chromatography. A.

[6]  Uwe Gottschalk,et al.  Bioseparation in Antibody Manufacturing: The Good, The Bad and The Ugly , 2008, Biotechnology progress.

[7]  A S Rathore,et al.  Process analytical technology (PAT) for biopharmaceutical products: Part I. concepts and applications , 2010, Biotechnology and bioengineering.

[8]  Kurt A Brorson,et al.  Advances in clone selection using high‐throughput bioreactors , 2010, Biotechnology progress.

[9]  Gary P. Pisano,et al.  The Development Factory: Unlocking the Potential of Process Innovation , 1996 .

[10]  Uwe Gottschalk,et al.  Process chromatography : Five decades of innovation , 2007 .

[11]  Uwe Gottschalk,et al.  New Q membrane scale-down model for process-scale antibody purification. , 2006, Journal of chromatography. A.

[12]  M. Butler,et al.  DNA spike studies for demonstrating improved clearance on chromatographic media. , 2009, Journal of chromatography. A.

[13]  Gary Walsh,et al.  Biopharmaceutical benchmarks 2010 , 2010, Nature Biotechnology.

[14]  Steven Kozlowski,et al.  Current and future issues in the manufacturing and development of monoclonal antibodies. , 2006, Advanced drug delivery reviews.

[15]  Jörg Thömmes,et al.  Alternatives to Chromatographic Separations , 2007, Biotechnology progress.

[16]  Begoña Calvo,et al.  Therapeutic monoclonal antibodies: strategies and challenges for biosimilars development. , 2012, Current medicinal chemistry.

[17]  Cristiana Boi,et al.  Membrane adsorbers as purification tools for monoclonal antibody purification. , 2007, Journal of chromatography. B, Analytical technologies in the biomedical and life sciences.

[18]  Gary W. Loveman,et al.  Starting over: Poland after communism , 1995 .

[19]  R. Twyman,et al.  Commercial aspects of pharmaceutical protein production in plants. , 2013, Current pharmaceutical design.

[20]  Jeff Davis,et al.  Use of Process Data To Assess Chromatographic Performance in Production‐Scale Protein Purification Columns , 2003, Biotechnology progress.

[21]  Abhinav A Shukla,et al.  Recent advances in large-scale production of monoclonal antibodies and related proteins. , 2010, Trends in biotechnology.

[22]  Rainer Fischer,et al.  Molecular farming of pharmaceutical proteins using plant suspension cell and tissue cultures. , 2013, Current pharmaceutical design.

[23]  Vijay P. Singh,et al.  Disposable bioreactor for cell culture using wave-induced agitation , 1999, Cytotechnology.

[24]  Raja Ghosh,et al.  Protein separation using membrane chromatography: opportunities and challenges. , 2002, Journal of chromatography. A.

[25]  P. Alves,et al.  Rational design and optimization of downstream processes of virus particles for biopharmaceutical applications: current advances. , 2011, Biotechnology advances.

[26]  A. Rathore,et al.  Quality by design for biopharmaceuticals , 2009, Nature Biotechnology.

[27]  R. Deshpande,et al.  Serum-free suspensin large-scale transient transfection of CHO cells in WAVE bioreactors , 2006, Molecular biotechnology.

[28]  Sanchayita Ghose,et al.  Defining process design space for a hydrophobic interaction chromatography (HIC) purification step: Application of quality by design (QbD) principles , 2010, Biotechnology and bioengineering.

[29]  Vijay Govindarajan,et al.  The Other Side of Innovation: Solving the Execution Challenge , 2010 .

[30]  Thanmaya Peram,et al.  Using precipitation by polyamines as an alternative to chromatographic separation in antibody purification processes. , 2010, Journal of chromatography. B, Analytical technologies in the biomedical and life sciences.

[31]  Kurt Brorson,et al.  The need for innovation in biomanufacturing , 2012, Nature Biotechnology.

[32]  Clayton M. Christensen,et al.  Disruptive Technologies: Catching the Wave , 1995 .

[33]  Paul J. Mcdonald,et al.  Selective antibody precipitation using polyelectrolytes: A novel approach to the purification of monoclonal antibodies , 2009, Biotechnology and bioengineering.

[34]  M. S. Levy,et al.  Framework for the Rapid Optimization of Soluble Protein Expression in Escherichia coli Combining Microscale Experiments and Statistical Experimental Design , 2007, Biotechnology progress.

[35]  B. Rehm,et al.  In vivo production of scFv-displaying biopolymer beads using a self-assembly-promoting fusion partner. , 2008, Bioconjugate chemistry.

[36]  Judy Glynn,et al.  Process-Scale Precipitation of Impurities in Mammalian Cell Culture Broth : If certain engineering challenges can be addressed, precipitation may prove to be a valuable tool for antibody purification , 2008 .

[37]  T Etcheverry,et al.  Performance of small-scale CHO perfusion cultures using an acoustic cell filtration device for cell retention: characterization of separation efficiency and impact of perfusion on product quality. , 2000, Biotechnology and bioengineering.

[38]  Yuri Gleba,et al.  Immunoabsorbent nanoparticles based on a tobamovirus displaying protein A , 2006, Proceedings of the National Academy of Sciences.

[39]  Jörg Peters,et al.  Implementation of a crystallization step into the purification process of a recombinant protein. , 2005, Protein expression and purification.

[40]  M. Odabaşı,et al.  A novel adsorbent for protein chromatography: supermacroporous monolithic cryogel embedded with Cu2+-attached sporopollenin particles. , 2011, Journal of chromatography. A.

[41]  F Meuwly,et al.  Potential of cell retention techniques for large‐scale high‐density perfusion culture of suspended mammalian cells , 2003, Biotechnology and bioengineering.

[42]  C. Sheridan Fresh from the biologic pipeline—2009 , 2010, Nature Biotechnology.

[43]  Michael Rubacha,et al.  Demonstration of Robust Host Cell Protein Clearance in Biopharmaceutical Downstream Processes , 2008, Biotechnology progress.

[44]  Marcel Ottens,et al.  Phase behavior of an intact monoclonal antibody. , 2007, Biophysical journal.

[45]  Ron Sanchez,et al.  Preparing for an Uncertain Future: Managing Organizations for Strategic Flexibility , 1997 .

[46]  Steven M Cramer,et al.  Improved process analytical technology for protein a chromatography using predictive principal component analysis tools , 2011, Biotechnology and bioengineering.

[47]  Uwe Gottschalk,et al.  Single-use disposable technologies for biopharmaceutical manufacturing. , 2013, Trends in biotechnology.

[48]  Ken G. Smith,et al.  The interplay between exploration and exploitation. , 2006 .

[49]  J W Larrick,et al.  Antibody engineering at the millennium. , 2000, BioTechniques.

[50]  John Hickey,et al.  Profiling of host cell proteins by two‐dimensional difference gel electrophoresis (2D‐DIGE): Implications for downstream process development , 2010, Biotechnology and bioengineering.

[51]  U. Gottschalk Disposables in downstream processing. , 2009, Advances in biochemical engineering/biotechnology.

[52]  Clayton M. Christensen The Innovator's Dilemma: When New Technologies Cause Great Firms to Fail , 2013 .

[53]  J. Birkinshaw,et al.  Building Ambidexterity Into an Organization , 2004 .

[54]  F. Wurm,et al.  25 years of recombinant proteins from reactor-grown cells - where do we go from here? , 2009, Biotechnology advances.

[55]  Heinrich Arnold,et al.  Creating Growth with Externalization of R&D Results - The Spin-Along Approach , 2009 .

[56]  M. Kamarck,et al.  Building biomanufacturing capacity—the chapter and verse , 2006, Nature Biotechnology.

[57]  Jörg Thömmes,et al.  Membrane Chromatography—An Integrative Concept in the Downstream Processing of Proteins , 1995 .

[58]  Lynn Conley,et al.  Using partition designs to enhance purification process understanding , 2010, Biotechnology and bioengineering.

[59]  J.D. Sterman,et al.  Nobody Ever Gets Credit for Fixing Problems That Never Happened: Creating and Sustaining Process Improvement , 2001, IEEE Engineering Management Review.

[60]  Daniel Cummings,et al.  Integrated continuous production of recombinant therapeutic proteins , 2012, Biotechnology and bioengineering.

[61]  Ana M Azevedo,et al.  Chromatography-free recovery of biopharmaceuticals through aqueous two-phase processing. , 2009, Trends in biotechnology.

[62]  R. Florida,et al.  Gaining from Green Management: Environmental Management Systems inside and outside the Factory , 2001 .

[63]  W. Abernathy,et al.  The Productivity Dilemma: Roadblock t o Znnovation in the Automobile Industry , 1978 .

[64]  J. Barney Resource-based theories of competitive advantage: A ten-year retrospective on the resource-based view , 2001 .

[65]  J. Curling,et al.  The Development of Antibody Purification Technologies , 2008 .

[66]  Paul J. Mcdonald,et al.  Fragments of protein A eluted during protein A affinity chromatography. , 2007, Journal of chromatography. A.

[67]  M. Porter TECHNOLOGY AND COMPETITIVE ADVANTAGE , 1985 .

[68]  Joe X. Zhou,et al.  Basic Concepts in Q Membrane Chromatography for Large‐Scale Antibody Production , 2006, Biotechnology progress.

[69]  Brian Hubbard,et al.  Downstream processing of monoclonal antibodies--application of platform approaches. , 2007, Journal of chromatography. B, Analytical technologies in the biomedical and life sciences.

[70]  John Thrift,et al.  The "push-to-low" approach for optimization of high-density perfusion cultures of animal cells. , 2006, Advances in biochemical engineering/biotechnology.

[71]  Patrick Thompson,et al.  Defining process design space for monoclonal antibody cell culture , 2010, Biotechnology and bioengineering.

[72]  M. Kula,et al.  Isolation and Purification of Biotechnological Products , 2007 .

[73]  Rui Gan,et al.  Cell-free protein synthesis: applications come of age. , 2012, Biotechnology advances.

[74]  Clayton M. Christensen,et al.  The Innovator's Prescription: A Disruptive Solution for Health Care , 2008 .

[75]  F. Sanger,et al.  The disulphide bonds of insulin. , 1955, The Biochemical journal.

[76]  Arnold Picot,et al.  Managing strategic ambidexterity: the spin-along approach , 2013, Int. J. Technol. Manag..

[77]  Brian Kelley,et al.  Industrialization of mAb production technology: The bioprocessing industry at a crossroads , 2009, mAbs.

[78]  Eugene Russo Special Report: The birth of biotechnology , 2003, Nature.

[79]  Brian Kelley,et al.  Very Large Scale Monoclonal Antibody Purification: The Case for Conventional Unit Operations , 2007, Biotechnology progress.

[80]  Nuala Moran,et al.  Biotech innovators jump on biosimilars bandwagon , 2012, Nature Biotechnology.

[81]  Suzanne S. Farid PhD Senior,et al.  Chapter 12. Process Economic Drivers in Industrial Monoclonal Antibody Manufacture , 2008 .

[82]  F. Regnier,et al.  Flow-through particles for the high-performance liquid chromatographic separation of biomolecules: perfusion chromatography. , 1990, Journal of chromatography.