Biopharmaceutical Drug Development

Biologics, or biopharmaceutical drugs, are promising treatments with low side effects for several diseases including cancer, immunological disorderand infectious disease. The high cost of biologics treatment causing the low drug accessibility and affordability. Each year Thailand imports approximately 500-1,000 million Baht of these products from many foreign sources. 

CRI’s Translational Research Unit (TRU) is focusing on translating fundamental scientific research to solve national and global health issues using multidisciplinary cutting-edge technology. Since the pandemic of bird flu in 2004 in Thailand, Her Royal Highness Princess Chulabhorn realized that Thailand was in an urgent need of national health security for self-reliance on therapeutics. Biologics or biological products consist of variety classes of bioactive agents including vaccines, blood products, tissue therapy, cell therapy, gene therapy, and recombinant proteins. TRU main focus is currently on development of recombinant proteins and biologics with potential to be therapeutics, vaccines, diagnostics, and research reagents. Current focus is primarily but not limited to monoclonal antibody, virus like particle, and recombinant peptide hormone.

To ensure the seamless transition and preparation of product pipeline, CRI has integrated all necessary steps required for biologics drug development, which are lead screening, lead identification, lead optimization, characterization assay establishment, efficacy demonstration, process development, and proof of concept study. With the lighting speed of technology shift nowadays, CRI has been invested in state-of-the-art technology for product development and quality assessment tools to ensure the forefront research quality. Due to the translation goal, the research’s key considerations are the compliance to latest regulatory guideline, the simple and scalable process, and the continuous improvement of both technology and human resources.

For product development, a variety of approaches have been implemented such as hybridoma technology, biosimilars and in silico product design. Series of recombinant protein production technique are applied including different molecular technique, variety of expression systems (bacterial, insect, and mammalian cell), and various purification techniques (normal flow filtration, tangential flow filtration, ultracentrifugation, and chromatography).

Upstream and downstream process development is starting once lead molecule has been selected and optimized. Cell line development is performed in accordance to international guideline to ensure the compliance for regulatory registration. Harnessing the advancement of high throughput technology coupling with design of experiment and robotic machine expedite top clone selection as well as more relevant upstream process optimization comparing to traditional shake flask optimization and process selection. Shaker flask system is, however, still important due to its cost effectiveness and ease of operation. As a result, both paths are complimented each other during process development.

Product quality is the determination of product safety and efficacy. Moreover, product quality is the result of production process. It is important to utilize the risk assessment holistic knowledge of different expertise to identify critical quality attribute as well as experimentally demonstrate the critical process parameter known as quality by design (QbD). Collectively, it is crucial that cell line and process development has been performed in an iterative feed-back event to be able to identify the best performing clone and the optimum process to move forward. Product quality assay developed at TRU including both lot release testing and deep characterization. The wide arrays of assays were developed to orthogonally cover different aspects of product such as identity, purity/impurity, physical properties, strength and efficacy. A variety of more than 100 characterization methods ranging from basic to sophisticated techniques are utilized such as cell-based assays, high throughput or high-resolution kinetic binding interaction assays, chromatographic-based techniques, diverse mass spectrometry techniques, spectrophotometry-based assays, and capillary electrophoresis-based assays, etc.

TRU also has a capability to do small scale process development for biologics. TRU has collaborated closely with the Center for Biologics Research and Development (CBRD). The successful biologics developed with small scale process will be transferred to CBRD for further process development at larger scale in a more controlled environment and regulatory compliance.