Process Commercialization

Session Chairs:

• Anne E. Mohan, Merck & Co., Inc.
• Anna Opella, The Dow Chemical Company

Session Description:

Process development challenges encountered on the path to commercial success 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 products/projects across various industries, and review the key factors which have contributed to their successes.

*All session and speaker information is subject to change pending finalization

Schedule:

Abstracts:

API Process Development and Scale-up challenges en route to Validation

Francisco Guzman, Merck & Co., Inc.

Process development has been underway for a late stage small molecule drug substance (Active Pharmaceutical Ingredient (API)) program, not only to improve overall efficiency and yield but also to identify potential process risks such as mixing sensitivities, solid settling, and reaction stability at scale.  In preparation for the program’s first commercial scale campaign, efforts to mitigate risk through process modeling and experimentation were carried out.  True to form, unforeseen challenges arose during batch execution.  For example, one issue was that heat transfer expectations from modeling did not agree with observed batch performance as processing parameters were outside of any stressed conditions tested, which threatened the batch purity.  As the program moves toward validation, the technology transfer process to the commercialization site has introduced its own set of challenges that required further development to address differences in site environmental requirements and operating procedures.

Enabling the Best Science for an API Commercial Route via Cross-functional Collaboration

Anne E. Mohan, Merck & Co., Inc.

The final chemical transformation and isolation in the synthesis of an Active Pharmaceutical Ingredient (API), referred to as the Pure Step, is often chemically simple but scientifically, operationally and strategically the most challenging. Pure step development is critical because it is used to determine and support the critical quality attributes (CQAs) for the API, which will have lasting impacts on the process.  This presentation will detail specific challenges for an API that is isolated as a citrate salt, crystallized out of methanol and isopropanol.  This citrate salt is then formulated via direct compression to make the deliverable for the patient.  The salt crystallization is particularly challenging due to: (1) the propensity of the citrate salt crystal to form solvates, (2) the particle size control requirements, and (3) the variability in starting material purity.  The team has had to execute targeted, rapid process development in order to support pilot plant API batches which will supply clinical trials, and simultaneously tech transfer the process to the manufacturing site overseas.  This work has required not just the technical capabilities of the team, but has also required streamlined collaboration and flawless communication across both drug substance and drug product space.  This presentation will detail the comprehensive and hefty process development work which was executed to support this pure step, focusing on the drug substance crystallization, and the impacts on the drug product space.

Process Commercialization Learnings from a Specialty Chemical Business in an Era of Sustainability

Andrew Millward, The Dow Chemical Company

In a specialty chemical business, the main purpose of commercialization is to transition a new product from R&D through manufacturing to provide value to the end users.  Quality, safety and cost play the traditional major roles in successful implementation of a new offering.  Product life-cycle and sustainability are trending as a new aspect to guide process design in adding value for the customer.  We have found some common elements while investigating the hand-off from development to manufacturing, which can provide engineers a clearer understanding of what is needed to implement their process designs and improvements in a sustainable manner.  The audience will be presented with several narratives which illustrate these learnings.