BioPharm International - November 2022

BioPharm International - November 2022

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32 BioPharm International ® Manufacturing and Facilities 2022 eBook www.biopharminternational.com OutsOurcing Four components for a successful cell line development project Host cell line. Cell line development begins with choosing the right host cell line. Unsuitable cells can produce low titers or a low-qua lit y product, ultimately causing delays and inefficiencies. CHO cell lines are most frequently used as hosts because they have an established, decades-long track record, are easy to grow in suspension at large scales (2000+ L), and possess the cellular machinery required to carr y out appropriate post-translationa l modif i- cations, which can be critical to the function and quality profile of the protein. Biopharmaceutical developers should look for a vendor whose starting cell lines employ a metabolic selection system (2) rather than a system that involves toxic selection agents, such as methotrexate (MTX) and antibiotics. Such metabolic selection-based sys- tems allow for improved robustness in cell growth and viability properties, reduced risk of genetic instability, and ability to enable high titer production. Expression vector. After choosing the appropriate host cell line, a good vendor should provide an opti- mized expression vector capable of expressing high product titers after transfection. Developers need op- timized expression vectors to ensure stable expression with minimal secondary effects on the otherwise op- timized host cells. Ideally, a single expression vector should show utility for any type of molecule: mAbs, bispecifics, and biosimilars, among others. Media. A cell line development partner should be able to provide cell culture media and feed that is highly compatible with the host cell line. A secure sup- ply of that same media and feed supplements should be readily commercially available to purchase and use for any further process optimization and development and for good manufacturing practice (GMP) require- ments. It is also important to consider the future avail- ability of the cell culture media because assurance of supply is critical as production is scaled up. Process design. The facility and operations must be configured to enable efficient and easy scale-up of the new production cell line. Streamlined process design involves implementing intelligent, scalable technologies and software to monitor, control, and analyze critical process parameters and product qual- ity attributes. End-to-end solutions with integrated sensors and analytical software can reveal new pro- cess insights that can be used to gather information about host cell performance and optimize the cell line development process. Flexibility and control Living organisms, fluctuating supply chains, and shift- ing consumer markets all add variability to the produc- tion of biologics. As a result, maintaining flexibility is even more critical to biopharmaceutical experts than to manufacturers in other industries. In-house manufacturing gives the highest amount of control and oversight for end-to-end bioprocesses, but some vendors offer options that allow for significant freedom while still providing technical assistance. For example, developers often have the flexibility to choose which CMO to work with for production after complet- ing cell line development and optimization and further GMP cell banking (for master and working cell bank production). Some vendors also present multiple op- tions for how each project can be accomplished, which adds transparency and gives developers more control over which strategies and technologies are applied. Selected vendors also offer technology licensing options to create a middle ground between outsourc- ing and in-house processes. Through technology li- censing, biopharmaceutical organizations can access expert-designed protocols, advanced technology plat- forms, and optimized materials from a vendor for use within their own facilities with their own team. It is important to note that some vendors charge licensing fees or milestone payments for using their cell-line development technology. These fees are often based on the molecule's success as it progresses through the various clinical phases. Other licensing agreements may include royalty fees in which the vendor receives a percentage of the molecule's annual revenues. Biophar- maceutical developers should consider reliable vendors that operate on a simple fee-for-service model to max- imize cost efficiency and retain complete control and ownership of their molecule. Better cell lines for better therapies Optimizing bioprocesses at every step, including cell line development, is key to delivering life-saving med- icines to patients with maximum speed and quality at an accessible cost. Biopharmaceutical companies should answer questions about their bioprocess devel- opment plans as early as possible, including how they will generate their new production cell lines, rather than devising sub-optimal strategies to solve problems that will undoubtedly arise as a result of poor plan- ning. By dedicating time to taking stock of their own internal capabilities, exploring options for outsourc- ing, and weighing the right priorities, biopharmaceu- tical developers can give their therapeutic molecules the best chance of remaining viable through every phase of development process, manufacturing stages, regulatory approval, and commercialization. References 1. R . M . L u , e t a l ., J o u r n al o f B i o m e d i c al S c i e n ce 7, 1–30 (2020). 2. B. Tihanyi and L. Nyitray, Drug Discover y Today: Technologies 38, 25–34 (2020). ■

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