Cambridge Healthtech Institute’s 5th Annual

Continuous Processing in Biopharm Manufacturing

Improving Process Integration and Control

August 12-13, 2019

 

Whether you are implementing the full end-to-end Integrated Continuous Biomanufacturing, or a hybrid version of the technology, and or are considering it in one way or another, continuous bioprocessing has become a household word among biopharma companies. Continuous manufacturing has the potential to increase the efficiency, flexibility, agility and robustness of manufacturing by reducing the number of steps and holds, utilizing smaller equipment and facilities, improving product quality and enabling real-time release.

CHI’s 5th Annual Continuous Processing in Biopharm Manufacturing invites researchers to share their latest endeavors in developing up- and down-stream continuous processes from lab to GMP, and in exploring strategies and technology enablers for continuous bioprocessing of novel products, process intensification and advanced process controls.

 

 

Final Agenda

 

Monday, August 12

7:30 am Short Course Registration Open and Morning Coffee


8:30-11:00 Recommended Short Course*

SC5: Saving Time in Process Development with Next-Generation Methods: PAT, Hybrid Modeling, Process Simulation, mDoe and iDoE

Instructors: Gerald Striedner, PhD, Associate Professor, Biotechnology, University of Natural Resources and Life Sciences, Vienna (BOKU)

Mark Dürkop, PhD, Project Leader, Biotechnology, University of Natural Resources and Life Sciences, Vienna (BOKU)

Moritz von Stosch, PhD, Senior Manager, Drug Substance, Technical R&D, GSK Vaccines

In this short course, we show how a more accurate design space can be defined that provides increased flexibility for process operation based on the iDoE-hybrid modeling strategy. We also show how advanced monitoring strategies support the tracking of the deviations and how these methods can readily be developed from the iDoE data. It will be illustrated how the combination of the hybrid model with monitoring can directly be exploited for process control, thus naturally evolving the last step of the QbD roadmap.

11:00 Main Conference Registration Open

PROCESS INTENSIFICATION AND CONTROL

12:30 pm Chairperson’s Opening Remarks

Robert Dream, Managing Director, HDR Company LLC

12:40 KEYNOTE PRESENTATION: Transformation to a New Intensified Process Platform

Souquet_JonathanJonathan Souquet, PhD, Head, Global Development and Launch, Technology & Innovation, Merck KGaA

This presentation will illustrate the evolution of Merck’s drug substance manufacturing platform from traditional to intensified process solutions. Technology development, control strategies, business case and implementation tactics will all be summarized to provide an end to end view of this transformation.

1:10 Upstream Process Intensification and Implication for Downstream Processing

Kreye_SteffenSteffen Kreye, PhD, Lab Head Upstream Development, Bayer AG

Upstream Process Intensification holds great promise to increase space-time-yield, maximize and adapt plant utilization and reduce cost of goods. Several attractive options for intensifying upstream processes have emerged in the last years. Depending on projects’ requirements each upstream mode has its pros and cons. Different hand-shake scenarios between upstream and downstream operational modes to handle high titers and / or high harvest volumes are presented.

1:40 Application of Automated Sampling towards Development of an Intensified Perfusion Platform

Franklin_JaredJared Franklin, MSc, Senior Research Engineer, Continuous Manufacturing Skill center, Sanofi

In order to better develop an intensified perfusion platform, our team implemented an automated sampling device to acquire more data. Using the device to collect harvest samples around the clock, we were able to greatly increase our sampling cadence. The increased volume of data we have been able to acquire has enabled the advancement and validation of new PAT, while lessening our team’s workload with regards to bioreactor sampling.

2:10 Refreshment Break

2:30 Advance in Real Time Monitoring and High Throughput Analytics for Biopharmaceutical Manufacturing

Aich_UdayanathUdayanath Aich, PhD, Associate Director, Analytical Science and Technology, Bristol-Myers Squibb

With the increase of emerging next-generation manufacturing processes (to reduce cost, increase speed and improve quality), regulatory expectation and life cycle management of Bio-therapeutic create a demand for novel analytics. This presentation will focus on the advance in state-of-art technologies for real-time monitoring and high throughput technologies for the analysis of product attributes and process parameters.

3:00 Developing a Fully Automated and Integrated Continuous Downstream Process

Taylor_LouiseLouise Taylor, BSc., Downstream Scientist, Biologics, Centre for Process Innovation

This presentation will describe the steps taken by a UK-based consortium of biopharmaceutical manufacturers to develop a fully automated and integrated continuous downstream platform. The overarching process control strategy allows a single operator to start up, run and shut down an entire downstream process consisting of up to nine unit operations from capture chromatography through to final formulation. Furthermore, the use of automated in-process sampling and at-line analytics enables the use of this platform in a GMP environment.

Pall_Biotech3:30 Process Characterization for Continuous Bioprocessing of Monoclonal Antibodies – Path Towards Bioprocessing 4.0

Dana Pentia, PhD, Senior Manager, Research and Development, Pall Biotech
Julie Grace, Manager, Bioprocess Specialist Team, Scientific Laboratory Services, Pall Biotech

An integrated continuous process is expected to run autonomously. This requires development of control strategies for variations which can occur in the process. Here we present developing a fully integrated automated lab scale continuous bioprocessing for monoclonal antibodies. QbD and MVDA, developing automation strategies, open the gates to Bioprocessing 4.0.

3:45 Session Break


3:55 Plenary Keynote Session View details

5:00 Grand Opening Reception in the Exhibit Hall with Poster Viewing (Sponsorship Opportunity Available)

6:30 End of Day

 

Tuesday, August 13

7:30 am Registration Open and Morning Coffee

INTEGRATED CONTINUOUS PROCESSING – CHALLENGES AND LESSONS LEARNED

7:55 Chairperson’s Remarks

Daniel F. Milano, PhD, Senior Development Engineer, Conjugation Process Development, ImmunoGen, Inc.

8:00 CQAs Challenges and Impact on End-to-End Integrated Continuous Biomanufacturing

Dream_RobertRobert Dream, Managing Director, HDR Company LLC

Continuous manufacturing has the potential to increase the efficiency, flexibility, agility and robustness of manufacturing by reducing the number of steps and holds, utilizing smaller equipment and facilities, improving product quality and enabling real-time release. In this presentation, we will examine the impact of the parameters that appears to change the outcome of the final product, such as:

  • What might go wrong (attribute)?
  • What are the consequences (severity)?
  • What is the likelihood it will go wrong (probability)?

8:30 KEYNOTE PRESENTATION II: An Integrated BioProcess for Continuous Processing at FIH, Late Stage, and Commercial

Ping Y. Huang, PhD, Director and Head, BioProcess Development, AbbVie at Redwood City

The concept of Integrated Harvest & Purification (IRP) is proposed and demonstrated that all unit operations from harvest to purified bulk can be integrated into one unit and processed in six hours. An IRP block that significantly reduces processing time, buffers, and manufacturing footprint, is being constructed for continuous processing at pilot and FIH stage.

9:00 Taking Lessons from Small Molecule Continuous GMP Manufacturing

Roberts_JeffreyJeffrey Roberts, PhD, Senior Research Scientist, Small Molecule Design and Development, Eli Lilly and Company

The use of continuous manufacturing has been highlighted as an important element in the modernization of the pharmaceutical industry. Eli Lilly and Company has developed considerable experience leveraging continuous manufacturing to enable development of small molecule drug substances and drug processes, and implementation of these processes in GMP facilities. This presentation will provide an overview of the continuous processing technologies and strategies that have been recently applied to projects in Lilly's portfolio.

9:30 Advances in Fed-Batch Process Intensification: High Productivity Harvest Using XCell™ ATF

Bonham-Carter_JohnJohn Bonham Carter, Director, Cell Culture & Clarification Business, Sales, Repligen

How can I gain from process intensification with the least effort? Should I retrofit my facility to become continuous or not? Is it possible to introduce intensification changes in late clinical or post commercial phases?


9:45 Coffee Break in the Exhibit Hall with Poster Viewing (Sponsorship Opportunity Available)

CONTINUOUS DOWNSTREAM PROCESSING

10:30 Selection of the Best Multi-Column Chromatography System for Continuous Downstream Processing

Yu_ChimingChiming Yu, PhD, Associate Director, Downstream Process Development, Boston Institute of Biotechnology

This study establishes a detailed comparison and selection guidance between four MCC systems (BioSC, AKTA pcc, BioSMB, Octave). All four systems use different technologies, configurations and control strategies, and all can perform continuous purification automatically with proper software settings. Using MCC, when compared with batch processing, the total volume of the resin can be reduced by 60-80%, with 50% reduction in process time and 25% reduction in buffer consumption, translating into potentially significant cost savings.

11:00 Viral Clearance Validation across Continuous Capture Chromatography

Srinivas Chollangi, PhD, Downstream Manager, MS&T, Bristol-Myers Squibb

We have compared several multi-column formats (2-, 4- and 6-column) and the impact of process parameters such as resin type, feed titer, feed flow rates, % breakthrough and process duration on optimal performance during continuous capture. We show that cGLP viral validation studies can be successfully executed using continuous chromatography and a scale-down model can be generated using standard chromatographic skids. Further insights will be shared on viral clearance across start-up, steady state and shut-down phases as well as effective cleaning strategies.

11:30 Continuous Solvent/Detergent Virus Inactivation Using a Packed-Bed Reactor

Martins_DuarteDuarte L. Martins, MSc, PhD Student, Lab of Protein Technology & Downstream Processing, University of Natural Resources & Life Sciences

Continuous virus inactivation has been overlooked while the biopharma industry moves towards continuous integrated processing. A novel continuous virus inactivation setup, which has several advantages over other approaches, is presented. In a case study solvent/detergent treatment was used to completely inactivate two industry-standard virus models (X-MuLV and BVDV) in a truly continuous mode. Control experiments confirmed that the continuous setup is as effective as the batch incubation.

Millipore_Sigma_purple 12:00 pm Finding Hidden Opportunities for Facility and Process Intensification Beyond Perfusion Production and Continuous Capture

Ryan_ShannonShannon Ryan, PhD, Associate Director, Downstream Process Integration, BioContinuum™ Platform, MilliporeSigma

Advances in intensified processes have primarily focused on perfusion production and continuous capture and significant strides have occurred in these unit operations. With these successes, focus on supporting processes and additional unit operations will become increasingly important to drive cost, risk reduction and efficiency benefits. We will present several opportunities for intensification across upstream, downstream and facility considerations with quantification of benefits and holistic value derived from these intensification efforts. 

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

CONTINUOUS PROCESSING OF NOVEL PRODUCTS

1:55 Chairperson’s Remarks

Srinivas Chollangi, PhD, Downstream Manager, MS&T, Bristol-Myers Squibb

2:00 Challenges in Continuous Manufacturing of Exosomes

Grube_AndrewAndrew Grube, Principal Assoc Scientist, Codiak Biosciences

2:30 Advancing Our Understanding of Continuous Antibody-Drug Conjugate (ADC) Processing

Milano_DanDaniel F. Milano, PhD, Senior Development Engineer, Conjugation Process Development, ImmunoGen, Inc.

Scale-up of ADC manufacturing brings the same engineering challenges of biopharmaceutical manufacturing. Additional considerations for handling and containing highly potent cytotoxic agents during scale-up is paramount. One way to address the challenges of scaling ADC manufacturing processes is using continuous processing. Here, we describe our work investigating continuous conjugation reaction chemistry using principles adapted from the field of flow chemistry and implementation of novel technologies to enable continuous purification of ADCs following conjugation.

3:00 Low-Cost, Highly Intensified Viral Vaccine Manufacturing

Luitjens_AlfredAlfred Luitjens, PhD, Director, Cell Technology, Batavia Biosciences

A consortium of Batavia Biosciences and Univercells, funded by grants from the Bill & Melinda Gates foundation, have developed a vaccine manufacturing platform that applies the latest process intensification technologies. Based on a high cell density fixed-bed bioreactor combined with high efficiency purification membranes and state-of-the-art process intensification know-how, we can increase process output by a factor of up to 80-fold. We will present the technologies and data obtained from the first target vaccine, a Sabin inactivated polio vaccine (sIPV), developed on this platform.

3:30 Continuous Manufacturing in Microbials: Drawbacks and Possibilities

Slouka_ChristophChristoph Slouka, PhD, PostDoc, Institute of Chemical, Environmental and Bioscience Engineering, TU Wien

Continuous processes using E. coli with different model proteins reach maximum in productivity after 30 hours upon induction on a mixed feed system with lactose. A subsequent drop in productivity leads to a complete non-producing culture after 4 days of cultivation. Online and at-line flow cytometry using PI as dye reveal, that two subpopulations during the cultivation. Total amount of the respective populations affects the net productivity during the induction.

4:00 Refreshment Break in the Exhibit Hall with Poster Viewing (Sponsorship Opportunity Available)

4:45 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.

Comparison and Selection Guidance for MCC System in Continuous Downstream Processing

Moderator: Chi-Ming Yu, PhD, Assoc Director, Downstream Purification, Boston Institute of Biotechnology, LLC

  • The differences: max columns, max flow rate, price, software, hardware, brand name
  • The applications: clinic/commercial, quantity, stability, upstream process
  • The one: why, when, how
  • The future: the ideal MCC system
  •  

What You Need to Know About End-to-End Continuous Bioprocessing

Moderator: Robert Dream, Managing Director, HDR Company LLC.

  • Challenges and opportunities
  • Need-based analysis
  • Continuous biomanufacturing implementation now and in the future
  • Is continuous manufacturing the best solution for your biotech facility?
  • Continuous manufacturing as a tool for process intensification

 

5:45 End of Conference


6:00-8:30 Recommended Dinner Short Course*

SC6: Integrated Continuous Biomanufacturing – An Implementation Approach

Instructor:

Robert Dream, Managing Director, HDR Company Ltd.

The importance and value of continuous processing’s economic and sustainability advantages due to the modular nature of continuous processes means that the industry is able to adapt more rapidly to changing market demands. Factors other than scientific ones, are the barriers to change from batch to continuous production. The (bio)pharmaceutical industry has reached a stage that requires a change in the production paradigm. Continuous manufacturing is as productive and has a much smaller footprint of the manufacturing plant, avoiding multiple non-value added unit operations. This course will cover strategies to transition from batch to continuous, areas to implement continuous manufacturing (from upstream to fill-finish), step-wise approach to implementation, new technologies and impact of big data, and more.