Emerging Technologies

Session Chair:

• Jean Tom, Bristol-Myers Squibb
• Cliff Kowall, Lubrizol

Session Description:

New technologies or methodologies have the potential to Increase the efficiency and effectiveness of process development. In this session, we present topics in the emerging technology space with the potential to improve development of unit operations, process equipment, generation of data and data analysis to support process development. This session will cover the emergence of topics and may include talks on process analytical technologies, high-throughput automation, and process intensification.

Schedule:

High Throughput Automation, Data Analysis to Advance Process Development

This presentation describes statistical experimental design approaches for high throughput automated experimentation, and the resulting data analysis to guide process development of active pharmaceutical ingredients and intermediates. Laboratory automation drastically decreases the cost and effort associated with routine experimentation during process development. The experimental setup supports development and optimization of multiple unit operations, and includes automated charging, automated sampling, sufficient mixing, and temperature control. To fully realize the value of automated experiments, the experiments must be designed and analyzed in a way that balances speed and rigor, so that experimental findings can be rapidly incorporated into future experimentation. Experiments are designed using various statistically relevant strategies including factorial, screening, and optimal designs. The design helps to strategically allocate the experimental budget for a particular round of automated experiments, which are executed in parallel. Once the data is collected, it is rapidly analyzed by combining data visualization, statistical analysis, and modeling to transform the experimental results into usable process knowledge and guide further rounds of automated experimentation. Once the process design space has been thoroughly investigated, in-depth data analysis and modeling is used to guide experiments and pilot plant batches. A case study where this workflow was applied to an API reaction to guide scale up experimentation and plant condition selection is presented. The case study will discuss the practical implementation of the workflow, the challenges of using small scale models to guide larger scale experiments, and how the results were used to select robust, high yielding operating conditions.

The Impact of Process Analytical Technology (PAT) on Process Development

The development of process understanding using real time in-situ PAT tools during process development and optimization is becoming a more common practice in the Pharmaceutical industry. This has become increasingly more valuable to support quality by design and product filings with the FDA.

This presentation will highlight numerous PAT techniques that can be used to monitor and control unit operations that span the development steps from receipt of raw materials through final tablet content uniformity.

All the Buzz About Process Intensification and Energy Efficiency Through Dow Lens 

As the world’s population rises and new economies emerge, society requires novel solutions to meet its most basic needs, including energy, water, housing, food, health, and transportation. However, limited natural resources entail their efficient use while simultaneously enhancing the quality of life of current and future generations. In this respect, process intensification is becoming an immensely important tool to achieve overall sustainability of the chemical process industry and the reduction of our energy footprint through controlled plant size.

This talk will focus on two interesting examples pertaining efficient specialty polymer processing as well as efficient synthesis of specialty epoxy through appropriate reactor design. Specifically, single phase solution polymerization renders itself aptly for overall energy reduction by applying process intensification principles. In particular, energy intensive solvent recovery after polymerization results in high energy foot print. Selection of appropriate solvent to lower polymer solubility and form two phases i.e. polymer phase and solvent phase provides an energy efficient alternative. The heavier polymer phase can be separated using a decantation step after polymerization to remove up to 50% of the solvent leading to lower solvent separation costs. Criteria for solvent selection and its influence on process thermodynamics along with impact of processing conditions on important polymer properties will be discussed.

The second example will focus on development of a continuous process for specialty epoxies for lowering the energy footprint. In particular, batch processing of specialty epoxies, though beneficial in controlling temperature of exothermic reactions results in longer processing time and undesirable side products. Manipulating the reactor surface area to volume ratio results in tighter control of reactor temperature and enables safe continuous processing with up to ten-fold reduction in processing time. Development of continuous reactor designs for epoxy processing through modeling and experimental validation will be presented.