Factory of the Future Trends in Continuous Manufacturing Mark A. Butler Sr. Vice President IPS - Integrated Project Services
Velocity of Change Human Genome Project Cost $2.7B 13 years Sequencing is forcasted to cost $100-1 hour $5M vs. $400 Cost of a super computer in 1975
Disruptive Technologies
Back to the Future November 1620 20 1032 November 1 620 15 1 0 32 November 162050 1032
Facility of the Future Team Jim Breen J&J Gert Molgaard NNE Simon Shelley GSK Mark Butler IPS Nandita Kamdar J&J
ISPE Factory of the Future 2015 Facility of Future Programs: - USA Carolina March 2015 - India April 2015 - EMEA Germany May 2015 - USA NJ / DV September 2015 - China November 2015 - North Carolina March 2016 - Baltimore, MD April 2016 - Continuous Manufacturing - EMEA Germany April 2016 - Boston, MA June 2016
What is the Plant of the Future?
What will the Future of Pharma Manufacturing Look Like? Smaller footprints / modular facilities w/standardized layouts. Integration ti of SU (disposable) upstream and downstream processes. Closed systems w/facilities moving towards non-classified environments. Continuous Manufacturing more automation and PAT. Increasing complexity of global supply / value chains. Flexible, agile and adaptable plants to deliver on demand products. Distributed manufacturing. Multi-function / multi-product processing suites: intensification in smaller footprint, scalable, modular. Global rationalization of duplicated plants / supply chains moving towards global centers of manufacturing excellence and local supply chains.
Continuous Manufacturing Promoting Continuous Manufacturing in the Pharmaceutical Sector The Brookings Institution Washington, DC October 19, 2015 Under a cooperative agreement with FDA, the Center for Health Policy at Brookings held a workshop for industry, academia, and government partners to identify the major barriers to the adoption of continuous manufacturing, discuss regulatory policies and strategies that could help to address those barriers, and explore approaches to improving public and private sector alignment and collaboration to promote the adoption of continuous manufacturing. I don t know why it s not more widely used this is the future. Janet Woodcock, M.D., Director, Center for Drug Evaluation and Research (CDER), Food and Drug Administration (FDA)
OSD Continuous Manufacturing Compelling advantages can no longer be overlooked Barriers to implementation are softening Equipment and system suppliers are leading the way Collaborations among Academia, Business, vendors, non-profits and regulatory agencies are driving implementation www.fda.gov
Continuous OSD - Advantages Higher quality, more consistent product (integral PAT) Built on QbD Methodology (rapid Design Space development leads to streamlined filing) Development on commercial scale equipment Long-term cost savings Smaller footprint (40-90%)* Reduced capital investment (25-60%)* Reduced operating costs (25-60%)* Lower raw material and WIP inventories * Novartis Pharma AG/MIT Estimates
Traditional OSD Batch Processing Weigh/Dispense Wet Granulation, Blending Compression Coating Drying, Milling Unit operations typically performed in separate rooms on separate days WIP staging between unit operations consumes significant floor space Off-line quality tests/holds after unit operations create bottlenecks Commercial batch sizes up to 1500kg
Continuous OSD Manufacturing All unit operations close coupled in one suite, with no WIP between major unit ops Gravimetric feeders replace conventional weigh/dispense function Integral PAT ensures that coated tablets discharged from end of train meet specifications Manufacturing cycle time reduced from weeks to hours; complete batch manufactured in < one day
CM ENGINEERING SERVICES SCALE
Continuous OSD Technology Vendors Function Vendors Comment Material Characterization Feeding and Blending Wet Granulation and Drying Dry Granulation Compression Coating PAT Freeman Technology K-Tron, Gericke, Schenck, GEA ConsiGma GEA ConsiGma, Lödige, Glatt, LB Bohle, Thermo Fisher (Wet Granulation) Gerteis, Fitzpatrick, LB Bohle GEA Courtoy, Fette, KORSCH GEA ConsiGma, O Hara, Thomas, LB Bohle GEA, Bruker, JDSU, Innopharma Labs, Siemens, ABB, Optimal, Emerson FT4 Powder Rheometer facilitates characterization of flow properties for establishment of Design Space Gravimetric hygienic twin screw or auger feeders; compact design; stackable to utilize gravity and incorporate premixes; Gericke GCM continuous mixers utilize axial and radial dispersion Wet granulation: primarily twin screw extruders; Lödige offers alternatives (Ploughshare, CoriMix (CM)) Drying: GEA utilizes conventional fluid bed with segmented chamber; Glatt MODCOS rotary chamber insert allows conversion of batch machines; Lödige dryer is horizontal with integral screw conveyor Conventional roller compactors are essentially continuous processing machines Conventional tablet presses are essentially continuous processing machines GEA ConsiGma coater very high speed drum (90-100 rpm); O Hara and Thomas employ tunnel configuration Blend Uniformity, Moisture Content, Particle Size, Tablet Properties, Data Management, SCADA
Continuous OSD Collaboration Models Academia providing scientific knowledge, platforms for collaboration, and development facilities to foster advancement of CM devices, controls and processes Regulatory agencies advocating CM as the best opportunity for manufacturers to improve drug safety and accelerate the development and approval of affordable new therapies Industry Pharmaceutical manufacturers interested in leveraging QbD to streamline product and process development, ensure compliance and minimize COG Vendors developing eloping equipment, instrumentation and controls solutions and positioning themselves to satisfy anticipated demand
Publicized Collaborations Continuus Pharmaceuticals (Novartis-MIT) Rutgers University and Janssen Pfizer / G-CON / GEA GSK / GEA / Siemens VERTEX / Cystic Fibrosis Foundation C-SOPS Center for Structured Organic Particulate Systems CMAC Centre for Innovative Manufacturing in Continuous Manufacturing and Crystallization
Spin-out company of $65MM MIT/Novartis collaboration Developing breakthrough integrated continuous pharmaceutical manufacturing, from API synthesis through final dosage formation Novartis has initiated the technology transfer to its novel Technikum Plant in Basel, Switzerland Awarded Phase I SBIR grant from National Science Foundation to further development of ICM technology Opened new facility in Woburn, MA in April, 2015
Janssen has been partnered with Rutgers Engineering Research Center for Structured Organic Particulate Systems (C-SOPS) for over 9 years. Recently Janssen provided $6MM to support pharmaceutical continuous manufacturing research. Rutgers Engineers built a continuous direct compression tableting line, located at the campus in Piscataway and have expanded it to also include wet and dry granulated products.
Vertex Vertex successfully collaborated with Cystic Fibrosis Foundation Therapeutics, Inc. (CFFT) to develop KALYDECO using QbD methodology on GEA ConsiGma- 25 continuous manufacturing platform FDA approval of KALYDECO announced in March, 2015
Pfizer /GEA /G-CON Collaboration Portable Continuous Miniature Modular (PCMM) Rapidly deployable continuous processing system consisting of GEA ConsiGma-25 installed in G- CON modular POD INTERPHEX 2015 Best Technology Innovation Award Courtesy of Pfizer
Continuous Mixing & Direct Compression ConsiGma TM WG GEA web site
CONTINUOUS OSD MANUFACTURING All unit operations close coupled in one suite, with no WIP between major unit ops Gravimetric feeders replace conventional weigh/dispense function Integral PAT ensures that tablets discharged from end of train meet specifications Manufacturing cycle time reduced from weeks to hours; complete batch manufactured in < one day Courtesy of Gebrüder Lödige Maschinenbau GmbH
Business Case for CM Same continuous process for PD, Clinical & Commercial Production Eliminates scale-up, reduces tech transfer Production-on-Demand lowers inventory Modular Portable Construction reduces investment and provides recoverable assets PAT provides robust, adaptable process control and CPV Additional unit operations can be added (dry granulation, coating, encapsulation, packaging, etc.) to scale out operations 25
CM ENGINEERING SERVICES SCALE
Summary CM will continue to advance in market acceptance Modular and standardized solutions are readily available today Stick built custom solutions are more complex and require more industry knowledge Continuing Education and Training is required for Owners and Engineers alike to understand the new technologies.
Thank You! Mark A. Butler Sr. Vice President IPS Integrated Project Services mbutler@ipsdb.com Based on our history of predicting the Future we will likely Based on our history of predicting the Future we will likely over estimate the amount of change in the next two years and underestimate the amount of change in the next ten