Cambridge Healthtech Institute’s 3rd Annual
Continuous Processing in Biopharmaceutical Manufacturing
Integration and Implementation
Part of CHI's Ninth Annual The Bioprocessing Summit

August 21 - 22, 2017 | Westin Copley Place | Boston, MA

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Continuous processing is now being accepted as a novel approach to efficiently and cost-effectively produce biological products. Companies are aware of the potential benefits of this approach, which can not only lead to smaller facilities, lower capital and materials, but also enable increased productivity, higher product quality and consistency. However, all is not a bed of roses. Continuous processing still has many roadblocks to overcome before it can reach mainstream adoption. CHI’s 3rd Annual Continuous Processing in Biopharmaceutical Manufacturing has moved from “why” to “how” – exploring challenges in implementation, both within up-stream, down-stream, and end-to-end integration from up- to down-stream.

Final Agenda

Monday, August 21

8:00 am Short Course Registration Open

9:0011:30 Recommended
Morning Short Courses*

SC3: Advanced Process Control, Intensified DoE and Hybrid Modeling for Process Optimization and Characterization

* Separate registration required

11:30 Main Conference Registration Open

KEYNOTE PRESENTATIONS

1:00 pm Chairperson’s Opening Remarks

Richard D. Braatz, Ph.D., Edwin R. Gilliland Professor of Chemical Engineering, Massachusetts Institute of Technology

1:10 Model-Based Multivariate Monitoring and Control of QbD-Compliant Quasi-Continuous Integrated Pharmaceutical Production

Reiner_Hans_LuttmannReiner Hans Luttmann, Ph.D., Professor, Bioprocess Automation, Bioprocess Engineering, Hamburg University of Applied Sciences

This presentation includes the description of advanced data processing in a fully automated integrated production plant, consisting of a two step upstream followed by a four-step downstream line with cell clarification, removal of particles with micro-filtration as well as product concentration and purification with ultra-filtration and chromatography. Recursive production strategies are developed where a cell breeding, the protein production and the whole downstream line is operated both in series and in parallel. However, each main operation is shifted by one day. As a demonstration process, the production of potential Malaria vaccines with Pichia pastoris is intensively investigated. The production process is global observable and QbD compliant developed. This includes also process optimization with fully automated DoE-plants and the establishment of design spaces and control spaces.

2:15 Continuous Manufacturing for National Preparedness & Response

Kimberly Sciarretta, Ph.D., Health Scientist, Division of CBRN Countermeasures, Biomedical Advanced Research & Development Authority [BARDA], Office of the Assistant Secretary for Preparedness & Response [ASPR], U.S. Department of Health & Human Services

Sau (Larry) Lee, Ph.D., Deputy Director (Acting), Office of Testing & Research [OTR], Office of Pharmaceutical Quality [OPQ], Center for Drug Evaluation & Research [CDER], U.S. Food & Drug Administration [FDA]

Within the U.S. Department of Health & Human Services, the Food & Drug Administration (FDA) and the Biomedical Advanced Research & Development Authority (BARDA) have a collaboration around exploiting innovations in continuous manufacturing for the rapid response to chemical, biological, radiological & nuclear threats and/or reduce the costs with cGMP production of clinical scale batches.

2:45 Refreshment Break

DRIVERS AND TECHNOLOGIES ENABLING CONTINUOUS BIOMANUFACTURING

3:15 Continuous Bioprocessing: Enabling Technologies and Technology Needs

Karol Lacki, Ph.D., Chief Consultant, Karol Lacki Consulting AB

A continuous process for manufacture of a biological product will rely on successful conversions of established batch operations into continuous operations and on implementation of new technologies specifically developed with continuous bioprocessing in mind. However, it will require a higher level of process understanding and process control. To reach this level of understanding and operational robustness, many technological and operational challenges will need to be addressed. This talk will discuss these challenges.

3:45 How to Engage with Regulatory Agencies on Continuous Manufacturing

Stephanie_KrogmeierStephanie Krogmeier, Ph.D., Senior Director, Global Regulatory Affairs, Vertex Pharmaceuticals

The interest in continuous manufacturing in the pharmaceutically industry has grown significantly due to multiple advantages including improvements in flexibility, reliability and quality. However, concerns over technical, operational, and regulatory issues still remain. A critical component of successfully implementing continuous manufacturing is engagement with regulatory agencies. This session will discuss key approaches to successful health authority engagement as well as key learnings and examples from recent FDA and EMA interactions.

4:15 Session break

4:30 Breakout Discussions

This session provides the opportunity to discuss a focused topic with peers from around the world in an open, collegial setting. Select from the list of topics available and join the moderated discussion to share ideas, gain insights, establish collaborations or commiserate about persistent challenges. Then continue the discussion as you head into the lively exhibit hall for information about the latest technologies.

Topic: Continuous Biomanufacturing - An Implementation Consideration

Robert Dream, Ph.D., Managing Director, HDR Company LLC. 

  • Will continuous bioprocessing be applicable to my process and operation?
  • What type of equipment/system/control should I implement?
  • Do I need any training for existing operation, QC, QA, Maintenance, Engineering, etc. personnel/departments?
  • How do I perform my process validation? 
  • How do I define my batch? What defines my batch records?
  • As continuous Manufacturing requires continuous control of the process… what and how much of the data generated should I save for future reference?

 

Topic: Engaging with Regulatory Agencies on Continuous Manufacturing

Stephanie Krogmeier, Ph.D., Senior Director, Global Regulatory Affairs, Vertex Pharmaceuticals 

  • What have you found to be the most successful approach to engaging regulatory agencies or alternatively, can you provide an example of a mistake or misstep with respect to engaging Agencies?
  • What approaches have you tried to align across regulatory agencies?
  • What is the biggest challenge we face across the industry in our attempts to engage with Regulatory Agencies on Continuous Manufacturing?


Topic: Advanced Process Monitoring and Hybrid modeling - a basis for QbD/PAT implementation in  Mammalian Cell Culture Bioprocesses?

Gerald Striedner, Ph.D., Associate Professor, Biotechnology (BOKU), Principal Investigator, Austrian Center of Industrial Biotechnology (ACIB) 

  • Advanced on- and offline monitoring strategies
  • Implementation of hybrid modeling approaches in mAB production processes
  • Transferability of hybrid models along scales from shaker to laboratory and pilot scale
  • Towards Model Predictive Control (MPC) in bioprocesses

 

 

5:30 Grand Opening Reception in the Exhibit Hall with Poster Viewing

7:00 Close of Day

Tuesday, August 22

7:30 am Registration Open and Morning Coffee

PAT, PROCESS MODELING AND REAL-TIME, ONLINE MONITORING

7:55 Chairperson’s Remarks

Karol Lacki, Ph.D., Chief Consultant, Karol Lacki Consulting AB

8:00 FEATURED PRESENTATION: Process Modeling and Real-Time Control for On-Demand, Continuous Biomanufacturing

Richard_BraatzRichard D. Braatz, Ph.D., Edwin R. Gilliland Professor of Chemical Engineering, Massachusetts Institute of Technology

This presentation describes the construction of process models and their application to the real-time control of biologic drug production in a small-footprint biomanufacturing platform. An opportunity is the use of a “virtual” plant for the dynamic operations of the entire end-to-end biomanufacturing process. The virtual plant can guide the selection of a control strategy for each critical quality attribute (CQA), design of startup and shutdown operations, and control systems design.

8:30 Enabling Continuous Manufacturing through Data Science, Modelling and Advanced PAT Tools

Christoph_HerwigChristoph Herwig, Ph.D., Head of Research Area Biochemical Engineering, Institute of Chemical Engineering, TU Wien, Vienna, Austria

Continuous manufacturing (CM) is more than the continuous operation of individual process steps. CM needs strategies to link the process steps and to account for variations of the preceding step by the establishment to robust control strategies. This contribution provides structured approaches for gathering process understanding for integrated processing, providing this knowledge in the form of target oriented minimum models as well as real time solutions to enable model predictive control.

9:00 Process Controls, Predictive Models and Right-Time Release in Biologics Drug Substance Manufacturing

Steven_DoaresSteven H. Doares, Ph.D., Vice President, Global Manufacturing Sciences, Biogen

Biogen is implementing an end-to-end process control strategy for new biologics drug substance manufacturing, with a goal to significantly reduce process variability and potential batch failures. Under this control strategy, raw material impact is well understood through process characterization studies, and RMs for manufacturing are well understood through characterization testing and linked genealogies. Biogen also uses rapid analytical technologies to assess PQAs at the earliest possible intermediate steps (“right-time” testing).

9:30 Sponsored Presentation (Opportunity Available)  

9:45 Coffee Break in the Exhibit Hall with Poster Viewing

10:30 Continuous Online Monitoring and Feedback Control Using PAT Tool, Raman Spectroscopy for mAb Perfusion Process

Nikhil_RamsubramaniamNikhil Ramsubramaniam, Ph.D., Senior Scientist, Bioprocess Technology & Expression, Merck & Co.

Application of Raman spectroscopy as a process analytical technology tool for glucose monitoring and feedback control in an antibody perfusion process will be presented. An interval Partial Least Squares Regression model for glucose was developed wherein perfusion process parameters were changed in a stepwise manner. Implication of glucose feedback control at < 0.5 g/l in the bioreactor on cell culture, achieved by real-time Raman glucose prediction, will be discussed.

11:00 Micro/Nanofluidic Approaches for Continuous Processing and Monitoring of Biologics

Jongyoon_HanJongyoon Han, Ph.D., Professor, Department of Electrical Engineering and Computer Science and the Department of Biological Engineering, MIT

Ideas from microfluidics can be employed in all these aspects of biomanufacturing to significantly enhance the overall productivity, as well as the efficacy and safety of the final products. In this talk, I will showcase several examples, including microfluidic cell sorting utilized for advanced cell retention system for perfusion bioreactors, as well as nanofluidic system for continuous-flow multi-variate protein analysis for real time critical quality assessments.

11:30 Validating a Commercial Manufacturing Process Control System Supporting PAT and RTRT

Michelle_BaileyMichelle Bailey, Associate Director, GMP Operations, Continuous Manufacturing & Automation Validation, Vertex Pharmaceuticals, Inc.

The pharmaceutical industry is adopting continuous manufacturing models to drive efficiency and higher quality. These new technologies require effective approaches for validation. This presentation discusses challenges encountered and approaches taken to validate PAT for in-process control and real time release testing with an emphasis on determining a validation strategy and taking validation from the lab to the plant.

12:00 pm Continuous Chromatography and Its Role in Process Intensification

Liselotte MolanderLiselotte Molander, Senior Global Product Manager, GE Healthcare Life Sciences

Focus on process intensification and increased process control continues in the biopharmaceutical industry. One key driver is reducing production costs while maintaining product quality and throughput. Approaches such as continuous chromatography has potential to increase chromatography resin capacity utilization, reduce equipment footprint and resource consumption. This presentation will cover periodic counter current chromatography in and beyond affinity chromatography mAb capture applications. We will also review a process economy tool to assess impact/cost as well.

12:30 Luncheon Presentation (Sponsorship Opportunity Available) or Enjoy Lunch on Your Own

1:15 Dessert Refreshment Break in the Exhibit Hall with Poster Viewing

IMPLEMENTING CONTINUOUS PROCESSES

1:55 Chairperson’s Remarks

Steven H. Doares, Ph.D., Vice President, Global Manufacturing Sciences, Biogen

2:00 Intensification of a Multi-Product Perfusion Platform through Medium and Process Development

Andrew_ChangAndrew Chang, MSc, Principal Research Engineer, CMSC, Biopharmaceutical Development, Sanofi

The talk will detail perfusion case studies on pushing to high productivity and low perfusion rate, the application of a standardized approach to different biologics, and engineering and economic considerations for commercial scale.

2:30 Design Considerations for Implementation of a Continuous Chromatography Step into a Platform Purification Scheme

Rebecca Chmielowski-Wright, Associate Principal Scientist, Protein Purification, Merck & Co.

In this presentation, we evaluated a three versus four column periodic counter-current chromatography (3C-PCC versus 4C-PCC) to replace the Protein A affinity batch mode purification step. Metrics included ≥ 85% step yield, productivity increase of ≥ 2-fold, resin cost reduction by ≥ 25%, and comparable product quality to the batch mode process. The challenges and differences in scale and operation between 3C-PCC versus 4C-PCC will also be presented.

3:00 Integrated Continuous Manufacturing Progress and the Life Sciences Industry “Fad or Reality”

Robert_DreamRobert Dream, Ph.D., Managing Director, HDR Company LLC

Over the past decade, there have been significant advancements in science and engineering to support the implementation of continuous biopharmaceutical manufacturing. These investments along with the adoption of the QbD paradigm for biopharmaceutical development and the advancement of PAT for designing, analyzing, and controlling manufacturing have progressed the scientific and regulatory readiness for continuous manufacturing. The regulatory supports the implementation of continuous manufacturing using science- and risk-based approaches.

3:30 Refreshment Break in the Exhibit Hall with Poster Viewing

SCALING UP OF CONTINUOUS PURIFICATION PROCESS

4:15 3D Structure of Protein Precipitates and Fractal Dimension for Scale-Up of Continuous Precipitation

Alois_JungbauerAlois Jungbauer, Ph.D., Professor, Department of Biotechnology, University of Natural Resources and Life Sciences, Austrian Centre of Industrial Biotechnology (ACIB), Austria

The 3D structure of protein precipitates is still widely unknown, especially the implications of different precipitate structures on possible downstream applications for purification. We use wide field microscopy and cryo-TEM to visualize the structure of PEG precipitates. Lab and pilot scale precipitation have concluded that in continuous precipitation with reactors with narrow residence time distribution such as tubular reactors, it is not necessary to operate at steady state as confirmed by the fractal dimension of the precipitate flocs.

4:45 Development of a Continuous Purification Process for mAb and Scale-Up Exercise

Xavier_LeSaoutXavier Le Saout, Associate Manager, Biotech Process Sciences Technology & Innovation, Global Manufacturing & Supply, Merck Serono SA

To fulfil future bioprocess manufacturing requirements, innovation is key. A lot of intensifying DSP tools are in development and sometimes close to implementation as multi columns system, SPTFF or continuous operations. This presentation will cover most of these tools, highlighting their main advantages, limitations and their potentials for manufacturing implementation. Finally, cases studies using integrated DSP platform and platform scale-up will be discussed.

5:15 Close of Conference

6:008:30 Recommended
Dinner Short Course*

SC6: Integrated Continuous Biomanufacturing - An Implementation Approach: Planning, Technology, Regulatory, and Manufacturing Advantages to Present Robust Optimized Batch Manufacturing

* Separate registration required

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