Process Development

Celltrion provides feasibility and optimization studies for media development, cell culture conditions and purification of biopharmaceutical products grown in mammalian-cell culture.

Cell Culture & Harvesting

Celltrion maintains a strong team of molecular and cell biologists, protein biochemists, fermentation technologists and chemical engineers, all of who are trained and experienced in the development of production processes for mammalian-cell-protein therapeutics. All processes and development activities are performed with the strictest adherence to cGMP standards. Celltrion's facilities will support seed, master, and working cell-banking services with all appropriate monitoring and documentation to meet U.S. and E.U. regulatory requirements. Celltrion will also work with our clients to maintain and protect alternative sites of master and working cell banks. The manufacturing facility in Incheon will include four independent trains of bioreactors, each consisting of 20L, 100L, 500L and 2,500L inoculum seed bioreactors, and a 12,500L production bioreactor. For smaller volume clinical or commercial production, the 2,500L bioreactors can be harvested directly. Each bioreactor system will be provided with fully automated Clean-in-Place (CIP) and Sterilization-in-Place (SIP) capabilities. Two independent inoculum preparation suites will be available, and the bioreactor trains have been designed to allow production of more than one cell culture product at a time. The facility and bioreactor systems have been arranged to maximize gravity flow and achieve high inoculation success rates. The bioreactors are principally designed , to enable fed-batch production, but may be modified to accommodate perfusion culture technologies.

● Media and Buffer Preparation Areas A designated GMP material dispensing area will be immediately adjacent to the materials warehouse, where individual media and buffer "kits" can be prepared. Separate media and buffer preparation areas have been incorporated into the design, each supported by separate access airlocks and CIP systems. Water for Injection (WFI) will be used to prepare all media and buffer solutions, as well as all CIP cycle final rinses. Buffer solutions will be sterile-filtered and stored until use in sterile buffer hold tanks, or they may be filtered and used directly. Media will be sterile-filtered directly into the appropriate bioreactors, or sterile media hold tanks for smaller solutions.

● Harvest Area Cell separation can be carried out using centrifugation (Westfalia) and depth filtration, either alone or in combination. Tangential Flow Filtration (TFF) cell separation has not been designed into the facility, but may be accommodated if needed. A 15,000-liter sterile harvest vessel will be available to hold cell culture fluid at refrigerated or ambient temperatures.

Purification and Downstream Processing

Celltrion's facility is designed to offer standard and customized processes for protein product purification, including a range of chromatography column options, viral inactivation steps, and techniques for host cell protein, contaminant and adventitious agent removal. We are committed to collaborating with our partners to develop recovery techniques for each unique product to generate maximum recovery yield and cost effectiveness. Separate purification areas will be provided for initial purification (pre-viral inactivation), final purification (post-viral inactivation), and bulk drug substance filtration. The pre- and post-viral inactivation areas will be serviced by separate access airlocks, equipment cleaning areas and CIP systems. Each area is designed to accommodate a wide range of purification procedures, including affinity, ion exchange, hydrophobic interaction and gel chromatography, ultrafiltration/diafiltration (UF/DF), and viral inactivation procedures. Sterile product pool tanks have been provided to ensure bioburden control and enable holding and/or combination of product pools at refrigerated or ambient temperatures. Sterile bulk drug substance will be held refrigerated or frozen in controlled, designated areas of the cGMP warehouse.

Quality Assurance/Quality Control and Product Characterization

Celltrion will be equipped to perform all analytical methods to support environmental monitoring: raw material, in-process and Bulk Drug Substance (BDS) release testing; product characterization; and BDS stability testing (both real time and accelerated). The quality control testing laboratories, as well as Process and Analytical development areas, are adjacent to manufacturing areas. Celltrion's analytical team is qualified and highly trained on the battery of techniques required to ensure accurate testing and characterization of our clients' protein therapeutics. These include assays to detect contamination; sequencing, mapping, spectrometry and amino acid analysis for protein characterization; and genetic analysis of recombinant cell lines. We value the importance of properly evaluating product stability, purity and consistency and will work closely with our partners and clients to ensure that our quality control laboratories develop and carry out the appropriate assays. The quality assurance department of Celltrion will work within a strict cGMP environment, as it recognizes the critical role of regulatory compliance and documentation in our clients' success. Our clients will benefit from the uncompromising attitudes Celltrion holds toward Good Manufacturing Practices, whether that has to do with raw materials, manufacturing procedures, facility environment, computer systems, or document control.

Formulation and Finish

Celltrion's facilities are designed to manufacture biotherapeutics through bulk drug substances. Although we do not offer fill and finish services, we will be able to support our clients' efforts to secure such capabilities in Asia or elsewhere.

Celltrion as a Manufacturing Partner

Celltrion is designed to support the manufacture of a wide variety of protein-based therapeutics, including monoclonal antibodies. Celltrion's model of capacity utilization is flexible, providing an advantage that clients may not find elsewhere. Celltrion's flexible facility design and ability to rapidly expand capacity provides a variety of options and opportunities to address the manufacturing needs of our clients.