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Cell line development platform for SMEs to reduce the length and cost of biologic drug development

Periodic Reporting for period 1 - IcoCell (Cell line development platform for SMEs to reduce the length and cost of biologic drug development)

Reporting period: 2016-05-01 to 2017-04-30

Due to high development and production costs, biologic drugs are expensive for patients and reimbursement agencies ($45 per day vs. $2 per day in case of chemical drugs, on average), limiting the access to these therapies and burdening healthcare systems. To a great extent, this is because traditionally flexible and creative biotech SMEs currently lack rational engineering tools for mammalian cell line development, meaning that large initial investment in terms of capital and time is required to engineer a production cell line.
Icosagen Cell Factory (ICF) develops a platform for more rational, efficient and cost-effective development of mammalian cell lines for high-yield protein production. This platform utilizes cell lines with predefined integration sites at the most transcriptionally active genomic loci. By predefining the integration sites, more than 10x less clones have to be analysed to find cell line with high levels of recombinant protein production compared to the current random screening. In addition, initialization of the specific recombination-dependent integration of the expression unit and amplification of the recombinant DNA reduce additionally the need for the screening of large number of clones. The platform reduces the need for robotic systems and high-throughput screening facilities, while reducing also the time required for cell line development from 6-12 months to less than 3 months.
Advances in cell line development technologies are crucial to support the rapid development of biologics, where improvements in the timeline and the ease of generating high producing cell lines can contribute to the faster development of biosimilars and innovator products alike. Market introduction of the IcoCell technology results in better health outcomes through better availability of biologics, and cost reduction for healthcare systems.
The objective of the IcoCell project is to optimize and validate the IcoCell technology for market introduction. Successful implementation of the project would allow ICF to significantly increase the coverage of the needs of the customers who are developing therapeutic proteins. In addition to assisting them in pre-clinical phase, ICF would be able to help the customers to enter into the clinical phase of the drug development, and start serving more attractive and profitable client segments interested in GMP (Good Manufacturing Practice) grade biological therapeutics.
The project has been implemented according to the initial work plan. All deliverables were achieved and reported to the European Commission on time.
The Work Package 1 aimed to generate necessary tools and know-how for cell line development in later stages of the project. WP1 has been completed with the following results:
(1) The landing-pad cassettes (used for generation of IcoCell platform cell lines) were generated and the reporter gene expression was confirmed.
(2) The process of cloning CHO (Chinese Hamster Ovary) cells for generation of monoclonal cell lines was optimized – CHO-S cell clone highly efficient for cloning (effectively grows at low cell densities) was generated.
(3) The functionality of the recombination sites in the landing-pad was confirmed.
The development work resulted in the method for IcoCell cell line generation.
The major goal for Work Package 2 was to generate sufficient number of IcoCell cell lines using the methods and know-how obtained during the WP1. The IcoCell cell lines have been generated and tested, and the process of obtaining necessary regulatory documents is ongoing:
(1) The method for IcoCell cell line development (validated during the WP1) was used to generate more than 10 suitable IcoCell cell lines.
(2) Standard Operating Procedures (SOPs) useful for description of IcoCell cell lines have been developed, and validated by using these to test the cell lines.
(3) Optimized semi-automated method for cloning and high-throughput screening of CHO cell clones was generated.
The semi-automated method was used to generate IcoCell cell lines, and will be used for validation of the IcoCell cell lines for the development of producer cell lines of therapeutic proteins in WP3.
The overall objective of Work Package 3 is validation of the developed modified cell lines and preparation of the SOPs for production of different types of therapeutic proteins. Most of the activities of WP3 are planned for the second year of the project. However, different configurations of expression vectors for single and double subunit proteins have been already generated. Additionally, the generation of protein producer cell lines has been initiated, as well as the process testing different cell culture media form several suppliers.
In Work Package 4, ICF’s existing business plan was updated. The IcoCell project is ahead of the planned schedule in terms of business development: many new customer prospects have been directly contacted in international events and major conferences, current and potentially new customers have been approached with a proposals for cell line development, and the project and its interim results have been disseminated from a public interest perspective.
Compared to the current state-of-the-art, cell line development with IcoCell will be up to 50% less expensive and requires lower investment but still provides an improved combination of benefits in terms of speed, quality, quantity and usability. IcoCell technology will support the introduction of new biosimilars and lower manufacturing costs, providing an ever-increasing opportunity for biologics to penetrate more cost-sensitive indications, markets and target groups. This translates into better population health: quicker recovery times, fewer additional treatments, and improved quality of life.
According to our best knowledge, a few biotechnology companies have started developing technologies to address the same market gap, indicating the relevancy of the challenge and existence of the business opportunity. However, all these alternative technologies are still in a very early stage of development, meaning that market introduction of the IcoCell technology in the near future as planned has still the same socio-economic impacts as expected. So far, the main societal implication of the project is the increase of awareness about the IcoCell technology and the addressed challenge among relevant stakeholders and the general public. The expected socio-economic impacts of the IcoCell technology will start arising after the technology is introduced to the market in 2018.
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