8:50 am Chair’s Opening Remarks

Achieving Commercial Scale Continuous Flow

9:00 am cGMP Manufacturing Aspects of API Continuous Cooling and Antisolvent Crystallization for Kinetic Impurity Rejection

Synopsis

• Plant throughput kg/h was 200X larger than development scale. Run time in the
plant was 7X longer than in development. There was no startup transition waste
for the continuous evaporation, crystallization, and semi-continuous filtration
sections. Stop/restart was done 17 times with no diverting to waste
• Surge drums decoupled the upstream chemistry CM sections from the continuous
crystallization, which served to allow one section of the flow train to keep
running while the other section was down
• Broad RTD dampened out disturbances, and this fact was used in the divert
decisions. RTD numerical modeling was used, and necessary, for calculating lot
genealogy for all batches
• Cleaning frequency was adjustable. In this campaign, it was left to the judgment
of the cGMP operations and technical staff to decide when it was time to stop for a
cleanout, rather than specifying a fixed time duration – In general, it is best to keep
cleaning frequency adjustable rather than specify and validate a specific time

9:30 am Flow Chemistry as an Enabler to Speed up the Process Performance Qualification for Challenging Processes

  • Hongwei Yang Executive Director, Head of Flow Chemistry Technology, WuXi STA

Synopsis

• The potential of flow chemistry in accelerating clinical supply and PPQ of active
pharmaceutical ingredients
• The role of an experienced CDMO in promoting the implementation of flow chemistry
in pharmaceutical industry
• Cases sharing on the quick completion of PPQ for challenging processes applying flow
chemistry

10:00 am Continuous Flow in Med Chem: Helping Enable and Scale Challenging Chemistry in Early, Rapidly-Evolving Projects

Synopsis

• Medicinal chemistry programs move quickly and need to prepare molecules of
interest on scale rapidly to make key decisions
• Flow chemistry has become a highly useful tool for rapidly scaling technically
challenging chemistries
• We will discuss recent work from our team rapidly scaling and delivering key
intermediates in flow via photoredox catalysis and fast, mixing sensitive reactions

10:30 am Development of a Continuous Flow Regioselective DIBAL-H Reduction

Synopsis

• Strategy and criteria for rapidly developing a flow process
• Reactor design for increasing scale
• Execution of GMP manufacturing batch and troubleshooting needed along the way

11:00 am

Structured Networking & Morning Break

Synopsis

The perfect opportunity for face-to-face time with the key opinion leaders in
continuous chemistry.
Establish meaningful business relationships to build upon for the rest of the
conference and gain individual insight into the pioneering work ongoing.

11:45 am Development and Application of Electrochemical Capabilities in Flow

Synopsis

• Strategy for scaling electrochemistry to the kilogram scale
• Discussing key scaling parameters needed
• Understanding reaction mechanics for informed electrode selection and safety
control throughout an increase in scale

12:15 pm Enabling Atroposelective Syntheses via Simultaneous Processing of Antagonistic Chemical Events (SPACE)

Synopsis

• Optical resolution is a reliable method for separation of atropisomers but it is
plagued by a maximum-yield of 50%
• Axes of chirality can be thermally epimerized but this conflicts with conditions
required for crystallization (cooling)
• Continuous flow can be applied to resolve these competing needs, resulting in
high-yielding synthesis of atropisomers which in turn reduces consumption of
solvent and valuable chemical intermediates

12:45 pm Panel Discussion: Commercialization for Flow Chemistry – Where Are We Now & Where Are We Heading?

Synopsis

• What has worked best for you so far?
• What has not worked?
• How do you approach outsourced vs internal development? How do you prioritize?
• How can companies open source their research while still protecting their company’s IP and competitive edge
• Have the drivers for flow chemistry changed as the industry evolves? Which are most applicable today?
• What are the biggest hurdles/remaining gaps which pose difficulties for the development of flow processes?
• What is the end goal of flow chemistry? Individual unit operations or integrated continuous manufacturing (ICM)?
• How can the learnings from small molecule drug substance and drug product be applied to other modalities?
• As the need for specialized equipment grows, which industries can biopharma, API & fine chemical companies
turn to for flexibility & experience

1:30 pm

Networking Lunch

Tightened PAT for Premium Product Quality

2:30 pm Scalable Continuous Photochemical and Electrochemical Reactions: Reactors and PAT challenges and Current Gaps and Future Opportunities

Synopsis

• Presentation details to be confirmed shortly

3:00 pm Digitalization for Process Optimization and Control in Continuous Flow API Synthesis

  • Peter Sagmeister Senior Scientist, Research Center Pharmaceutical Engineering GmbH

Synopsis

• Introduction to autonomous continuous flow chemistry platform and advanced
data processing techniques
• Process Analytics and Control Technology for multi-step transformation
• Case studies on data-rich experimentation at an early development stage for
enhanced process understanding

3:30 pm Pharmaceutical Process Automation in the Design of the Factory of the Future

  • Thomas Roper Professor, Director, Department of Chemical and Life Science Engineering, Virginia Commonwealth University

Synopsis

• Challenges with traditional PAT on multi-step transformations
• Opportunities to use multi-faceted modeling to enhance product quality
• Approaches to continuous reaction automation

4:00 pm Chair’s Closing Remarks