CMC capability and GMP manufacturing capacity in line with international standards

Our CMC team has extensive international experience in CMC and plays a critical role in our drug development and production. As part of CMC function, we have established our process development and industrialization platform with competitive advantages through functions such as high-expression cell line construction, serum-free chemical defined media and cell culture process, protein purification, quality control for biologics production and concentrated fed-batch process. We have applied such platform in multiple clinical stages of various monoclonal antibody development projects and achieved rapid mass-production of drug products while ensuring product quality and safety.

We have established high-expression stable cell line construction and screening platform, which enables the generation of high-expression cell lines in a shorter timeframe. The platform is based on CHO cells and adopts the GS expression system. This involves a cell system with a chemical composition of medium suspension and domestication with a high-throughput screening system and a high-efficiency and high-expression screening method. With this platform, we are able to construct stable high-expression cell lines in a short time period, effectively shortening the time-frame needed from DNA to IND. Our in-house developed chemically-defined cell culture medium provides significant cost advantage and better quality control.

Our protein purification and formulation process adheres to QbD concept and DOE screening approach and develops monoclonal antibody and multi-specific antibody in a way to ensure high recovery yields, high-quality and high-purity of antibody products. In addition to our conventional fed-batch cell culture process, we also developed intensify upstream processes using Alternating Tangential Flow (ATF) technology which includes concentrated fed-batch and perfusion. Through this technology, cell culture density and productivity are greatly increased and the production scale can be miniaturized. It allows us to produce a large amount of antibody drugs in a small bioreactor. This capability is very important for building biological reserves in responding for emergencies.

We have established a quality control technology platform for covering raw materials, antibody manufacturing process, drug substance and drug product release test, which consists of a protein physicochemical analysis and structural characterization platform, a biological analysis and functional characterization platform, and QC laboratories which conduct testing of raw materials, water, air, environmental pathogens and particles to support GMP manufacturing processes, stability and release testing of drug substances and drug products to support clinical studies. With the quality control technology platform, we are able to conduct research and development activities and antibody production in compliance with the registration requirements of regulatory authorities, such as NMPA, FDA and EMA.

Our manufacturing activities are currently carried out at our facility in Beijing. The facility is designed and operated in compliance with GMP standards. Our quality control system has been validated/audited by regulators for multiple times and meets rigorous and comprehensive requirements under Chinese standards. We have built two 1,000L stainless steel bioreactor production lines, two 200L single-use bioreactor production lines, and a high capacity fill-and-finish injectable production line.As of the Latest Practicable Date, we were in the process of applying for a Pharmaceutical Manufacturing_世界杯预选赛中国队赛程 Permit for our existing manufacturing facilities and expect to receive the permit in the second half of 2021. In addition, we are developing a manufacturing facility featuring an 18,000m2 space for R&D, office and manufacturing functions and three 2,000L production lines.