Accelerating attribute-focused process and product development through the development and deployment of autonomous process analytical technology platform system.

Enabling real-time monitoring and control of the biomanufacturing processes through product quality insights continues to be an area of focus in the biopharmaceutical industry. The goal is to manufacture products with the desired quality attributes. To realize this rigorous attribute-focused Quality by Design approach, it is critical to support the development of processes that consistently deliver high-quality products and facilitate product commercialization. Time delays associated with offline analytical testing can limit the speed of process development. Thus, developing and deploying analytical technology is necessary to accelerate process development. In this study, we have developed the micro sequential injection process analyzer and the automatic assay preparation platform system. These innovations address the unmet need for an automatic, online, real-time sample acquisition and preparation platform system for in-process monitoring, control, and release of biopharmaceuticals. These systems can also be deployed in laboratory areas as an offline analytical system and on the manufacturing floor to enable rapid testing and release of products manufactured in a good manufacturing practice environment.

Micro sequential injection system as the interfacing device for process analytical applications.

It is an important and desirable capability to be able to control the quality and quantity of biological product by maintaining and adjusting bioreactor performance throughout its production duration. Amino acids are the building blocks of proteins. Scientists will need to ensure sufficient supply of amino acids as the substrates in the bioreactors as well as to control the excess level of undesirable free amino acid byproducts to maintain an optimum growth environment for cell culture. We have developed a compact and robust sample preparation platform capable of interfacing with analytical instruments to achieve bioreactor amino acids monitoring. We demonstrated the feasibility of this concept by incorporating an automatic amino acid sample preparation protocol to a micro sequential injection (µSI) system connected to an ultra-performance liquid chromatography system for real-time, at-line amino acid separation, and quantitation. The µSI system was configured into a "platform-like" sample preparation system that is able to accommodate future wet chemistry-type sample preparations. Its real-time amino acid results can be readily available to bioprocess scientists for quick decision making and design of their next experiment. Potential automatic feedback control mechanisms can be established through trigger events based on predetermined analytical signal thresholds so the system can communicate with facility infrastructure to control bioreactors in near real-time fashion. The proposed µSI system described in this paper can be widely used as an automatic sample preparation system connected to the front-end of analytical instruments to enable process analytical technology applications.