Creating cell lines with future manufacturability, cost of goods and speed in mind is of critical importance in today’s biopharmaceutical development. By working with our cell culture teams in our Slough (UK), Visp (CH), and Tuas (SG) sites, you will benefit from a recognized and stable cell line using our GS Xceed® Gene Expression System. The combination of host cell line, vector and stringency of selection enables us to provide our customers with high producing cell lines suited to fit a commercially relevant platform process.
Percentage of cell lines above different titer levels
Your cell line will be developed using procedures based on achieving high product titers and the desired product characteristics. Selection experiments carried out in miniature bioreactors with an abridged version of our platform manufacturing process will help to reduce risks at later stages and allow a seamless transition from development into cGMP manufacturing. Close interaction with regulatory authorities worldwide eases regulatory hurdles since these cell lines will be constructed, cloned and characterized according to current regulatory guidelines. Use of electronic notebooks enables real time data entry, reduces human error and offers full traceability.
Options for cell line development
At Lonza, you can benefit from a flexible approach to cell line construction that matches your priorities in terms of timelines, yield optimization and risk. Our team will discuss options in detail to determine the best scope to fit your project requirements. We are able to offer customized combinations for the following services:
Full Scope CLC is suitable for customers targeting higher titers. For example, products targeting the neurodegenerative disease market will require large quantity of product. We will screen more clones to find the highest titer clone. This program is also suitable for complex proteins that can be difficult to express. Our Full Scope CLC service
includes comprehensive clone generation and selection with supporting analytics to ensure high yielding cell lines that fit with the GS Xceed® Platform manufacturing process. Lead cell line candidates can be selected at 16 weeks from transfection.
Lightpath™ CLC is designed around
speed, which is achieved in part by screening fewer clones. This option is applicable for standard format
antibodies and Fc-fusion proteins that have a low risk manufacturability
profile. Manufacturability assessment is performed with a rapid in silico evaluation to ensure the
molecule is appropriate for this offering. Lightpath™ CLC
is designed to rapidly and cost effectively progress your candidates to a
stable, commercially viable cell line. Lead cell line candidates can be
selected at 12 weeks from transfection.
Multiplex CLC is designed to progress multiple candidates or variants to the Research Cell Bank (RCB) stage. This offering progresses multiple candidate cell lines simultaneously so that the most suitable can be selected for the final lead. More data on variants/candidates can be generated and analyzed with Multiplex CLC to support your decision-making process for the best candidate. Lead candidate cell lines for up to four candidates/variants can be selected at 12 weeks from transfection. Multiplex CLC can save 4 months on an overall development program compared to a traditional biologics development approach.
Ibex™ Design is our offering for your preclinical and IND needs through to clinical phase I. It includes a pioneering gene-to-vial package, delivering GMP drug product for your clinical phase 1 trials within 12 months, with an option to supply tox drug product in 9 months. To ensure speed to your milestones, Lonza guarantees the timelines of product supplied*.To further increase predictability for you, we will keep a manufacturing slot reserved for your clinical resupply. Benefit from our proven GS Gene Expression System® bioprocess platform and a holistic development strategy with the endpoint in mind.
*For antibodies and antibody like molecules. From receipt of the gene sequence. Subject to terms and conditions.
Mammalian Cell Banking
A dedicated cGMP unit within our licensed UK manufacturing facility is used to create master and working cell banks for subsequent manufacturing use. The cell banks are characterized in accordance with FDA and European regulatory agency requirements. For safety and security considerations, dual-site storage of all cell banks are maintained between our US and UK facilities.
Protein Sequence Variant Analysis
A protein sequence variant is an unintended amino acid sequence change within a region of a product. Any biological expression system is prone to generation of these variants, which may affect (inter alia) product efficacy and immunogenicity. Traditionally, detailed analysis of product variants is performed during Phase II/III of development once cell line and manufacturing process has been fully defined. This is usually performed as part of the reference standard characterization studies which are required for regulatory submissions. However this traditional, reactive approach provides no effective options should an issue be identified – either the process must be redeveloped or a different cell line taken forward. These options carry significant unforeseen costs and timeline impact.
In contrast, incorporation of advanced analytical tools into cell line development enables early, proactive detection of protein variants. Since variants may be generated during translation of mRNA in the ribosome, effective detection must be performed at the protein level rather than by DNA or mRNA sequencing alone. Our Protein Sequence Variant Analysis (PSVA) platform uses class-leading mass spectrometry methods including Electron-Transfer Dissociation and Ultra-High-Resolution Orbitrap mass detection. Our scientists apply advanced informatics to rapidly detect and quantify any amino acid substitutions in panels of candidate cell lines, or across processes.
This technology allows consistent detection of variants across the entire product sequence. Variants at levels as low as 0.004% have been confidently identified.
Since 2004, we have constructed more than 700 CHO derived GMP cell lines
Over 25 years, our GS Gene Expression System® has been continuously improved for robust technical performance. It is able to express a diverse range of biopharmaceuticals with high titers. The system is used within Lonza and is also available for out-license.