91成人短视频

Session Chairs

• Anne Mohan, Merck
• Kevin Joback, Molecular Knowlege Systems

Session Description

The process development challenges encountered on the path to commercial are often complex, daunting, and span both the technical and managerial realms.  The time required to overcome these challenges and deliver a robust, scalable, and efficient process can often be the determining factor for whether a product is launched.  Companies and investors depend on individuals, teams, and business processes that can consistently deliver an optimal process on schedule.  For these reasons, process development, optimization, and efficiency play key roles in the lifecycle and viability of a product.  In this session, we will discuss and provide case studies of the obstacles overcome for various products/projects across various industries, and review the key factors which have contributed to their successes.

Schedule:

Abstracts:

Bonsai Process Development

Ron Leng,The Dow 91成人短视频 Company

Increasing speed to market is a key to maximizing profitability in launching new technology and products.  The Process Development team tasked with developing the new process technology has the challenge of managing the triple constraint; that being time, scope, and resources.  There is an ever increasing drive to go faster with fewer resources.  So that leaves the team with how to manage the scope of developing the new process technology.  Process Development is all about making decisions.  The method I will discuss I call 鈥淏onsai Process Development鈥�.  The Bonsai Tree gardener carefully prunes the branches of the Bonsai tree in order to train the tree in the direction they desire.  Here the analogy is that the 鈥渢runk鈥� represents the exact commercial process, while the 鈥渂ranches鈥� are nodes where two or more options are considered.  Only one of these alternatives will become part of the final process.  It is at these nodes where time and effort can be either expended or conserved by how we approach decision making.  In the strictest sense any work or time spent on an alternate branch represents waste.  Realistically, some work needs to be done on the alternatives to make the right choice.  However, delaying decision making and working on the alternate branch too long is wasteful and can cause delays to the project, so the process developer needs to learn to prune these branches. The better we can frame up the problem statement or objective of the process step, define success and what is necessary for success, including rate limiting activities, the quicker we can get to the final commercial process.  Approaches and examples will be used to illustrate the Bonsai Process Development principles.

Scale-down to Scale-up More Efficiently

Mike Schultz, PTI Global Solutions

The time and cost required to scale-up a new technology has been well documented.  We can reduce the time and cost for scale-up by looking at the commercial design during the early stages of process development.  This forms a basis to then 'scale-down', prioritizing the key variables and unit operations required to optimize the design and reduce technical risk throughout scale up.   In addition, commercially proven unit operations can often be identified which can be adapted for the new process.  Real world examples will be used to illustrate the advantages of this approach. 

Enabling Rapid Process Development for the Endgame Steps of an API

Anne Mohan*, Azzeddine Lekhal, Russell Hensley, David Lamberto, Ivan Lee, Shane Grosser, Alexei Kalinin, Jingjun Yin, Tetsuji Itoh, Bangping Xiang, Margaret Figus, Yu He, Liam Corcoran, Eamonn Joyce, Thorsten Konekamp, Mick Lucey, Nick Rogus, Ruth Rosenthal, Khateeta Emerson, Glenn Spencer, Laura Artino, and Rich Varsolona 

Merck & Co.

The 2 endgame steps of an API synthesis involves a double Suzuki coupling reaction, the product of which is isolated by a mandelate salt formation, followed by a salt break and precipitation of the neutral API.  The Suzuki reaction of the penultimate step is particularly challenging both to execute and to understand due to the oxygen sensitivity of the catalyst and starting material, and to the sheer amount of impurities which can be formed during the reaction, respectively. The high number of impurities formed during the reaction makes the mandelate salt formation used to isolate the Suzuki product equally challenging, since impurity rejection is critical.  In parallel with the process development for the Suzuki, the Pure step has faced several fluctuations over the last 2 years.  The changing landscape of the product market has significantly impacted the Pure step specifically in the last ~6 months due to variations in both API demand and drug product formulation.  The potential shift from spray drying to conventional formulation has significantly impacted the process development and desired physical attributes of the API.  This poster will detail the comprehensive and hefty process development work which was executed to support the endgame steps, and their respective impacts on the broader program.