Safety in Process Development | AIChE

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With the ever-increasing need for companies to deliver value quickly, there is perhaps a tension that implies a need to trade safety for speed as new technologies are introduced. Such a trade is not only unacceptable, it is also unnecessary. This session will provide examples to answer the question: How can new processes be implemented rapidly and successfully without compromising on safety?

Session Chairs:

  • David Couling, Corteva
  • Pranav Karanjkar, Dow

Schedule:

TIME (EDT) PRESENTATION SPEAKER
11:00 AM Enablement of Highly Hazardous Processes using Continuous Flow Technology Kevin Nagy, Snapdragon Chemistry
11:30 AM Plant be Nimble. Balancing Safety and Speed at the Pilot Plant Scale Jon Van Regenmorter, Corteva Agriscience
12:00 PM Small changes, Big impact - How to embed safety into rapid development and scale-up of processes Megan Roth, Merck

Abstracts:

Enablement of Highly Hazardous Processes using Continuous Flow Technology

Kevin Nagy, Snapdragon Chemistry

The use of continuous flow technology offers several processing advantages in the manufacture of fine and pharmaceutical products, including the ability to carry out highly energetic and reactive chemistries while minimizing the process hazard.  These processes are enabled by several factors associated with the flow platform, including rapid heat transfer, low hold up volumes, economically achievable high-pressure reactors, and precise control over mixing rates.  One important, but less discussed benefit of flow reactors is the high reactor phi value, which imparts an innate reduction in the potential for hazardous conditions to arise due to unexpected loss of cooling.  

In this presentation, I will discuss Snapdragon’s approach to assessing and carrying out hazardous processes in the context of continuous flow reactions with two case studies.  The first example will cover Snapdragon’s approach towards carrying out extremely fast and energetic SnAr lithiation processes where we allow the reaction to achieve its adiabatic temperature rise.  The second example involves an ultra-high temperature (>300 °C) super-heated reaction that had a decomposition event well within the characteristic 50 °C limitation generally ascribed to in batch reactions.  In both cases, thermal characterization studies, process hazard assessments, detailed understanding of reaction kinetics and heat transfer performance, and incorporation of appropriate relief devices enabled successful operations.

 

Plant be Nimble. Balancing Safety and Speed at the Pilot Plant Scale

Jon Van Regenmorter, Corteva Agriscience

How do you balance need for speed with the requirements of process safety? What techniques and process can be employed to help balance these two important factors? These questions are relevant on a daily basis at the pilot plant scale where chemistry changes frequently and the target always seems to be moving. We’ll be looking a few different strategies to stay nimble without compromising safety or quality. These strategies include base case envelopes, roll-up procedures and work flow design. Join as we look at the challenges, strategies and a few examples.

Small changes, Big impact - How to embed safety into rapid development and scale-up of processes

Megan Roth, Merck

The Environmental & Process Safety Engineering (EPSE) group at Merck & Co., Inc., Kenilworth, NJ, USA has the responsibility to characterize the desired and undesired process chemistry for synthesis of pharmaceutical candidates in order to mitigate low/moderate risks and avoid high risk processes.  

An established staged approach is utilized for safety testing and evaluation of processes scaled-up to the kilo lab and pilot plant. However, as the pace of process development increases, in order to support safe scale-up of the best process it has become critical to embed safety into process development and adapt approaches to support timelines. This was done starting with early engagement of EPSE in advance of process scale-up, selectively pre-investing in process safety testing to flag significant safety concerns and influence the process chemistry.   To aid in flexibility as scale-up approaches and during scale-up, continuous communication is driven across the process development team, EPSE, and the scale-up facility, which is critical to ensuring safe scale-up as small changes during development can have a big impact on safety.   In addition, process development teams are proactively informed about the types of future process changes that may require safety re-evaluation and/or a facility set-up modification, which drives well-informed development decisions that support timelines while ensuring a safe scale-up.



Several examples will be provided that demonstrate the potential impact that small development changes can have on safety, emphasizing the importance of management of change during development and scale-up.