Rodon’s cell line development activities are performed as a stand-alone service or are fully integrated into a process development program. The development of cell lines producing a high yield of product is a key factor to reduce the production cost of biobiopharmaceuticals. For MABs and recombinant proteins Rodon can create vectors to express product using CHO platform. Protein yields of grams-per-liter range have been achieved using this system in chemically defined, animal-, component-free medium. This procedure is based on a simple workflow which allows obtaining a high-producing single cell clone in 13-18 weeks. Moreover, once a high producing pool is generated, the quality of the material is evaluated and it can be used to produce gram-per-liter quantities of material in 8-11 weeks.
The selection strategy has been designed to identify cell lines that are highly productive and have the ability to grow well in suspension culture in a fed-batch fermentation process.
The stability of the stable clone is evaluated to guarantee that after several passages their ability to express the protein is maintained. We have found that using this technology, even after 60 generations, the expression level of the stable clone is comparable to the earlier generations.
The production of therapeutic proteins for use in clinical applications is stringent and rigorously controlled. The burden of proof lies with the manufacturer, who must be able to demonstrate, using robust analytical procedures, the quality and consistency of the product and process.
Products from bioprocesses are complex molecules produced using complex manufacturing processes. No one range of tests fits all cases, a combination of complimentary and overlapping techniques is essential to demonstrate identity, structure, purity and potency of the product and assure the consistency of the manufacturing process. Critical scientific consideration of the analytical techniques capable of providing the necessary information, according to specifications of the product/process and regulatory issues is required.
At Rodon we have the experience to develop the required analytical procedures to assure product and process quality. Tests are designed in consideration of the relevant Pharmacopoeia (EU and US monographs) and regulatory guidelines (ICH, FDA and EMEA) and considering GMP practices.
For commercial biopharmaceutical products the stability of API, ancillary and drug products during storage and in use, should be investigated. Consideration should also be given to products used in pre-clinical and clinical investigations.
Prior to approval a detailed study of product stability should be finalised and conducted in consideration of relevant guidelines e.g. ICH. Evaluation of identity, purity, potency and strength of the biopharmaceutical products upon release and during storage is critical for regulatory and marketing purposes. Analytical methods to test those attributes that are susceptible to change and are likely to influence quality, safety and/or efficacy should be developed and eventually validated.
Rodon carries out the development of test methods, protocols and outsource final studies on stability of recombinant biopharmaceutical APIs, ancillary and drug products to assure the accurate profile of your biopharmaceutical product. Rodon provides in the stability program the complete range of ICH stability conditions test methods and, moreover, the development of methods to maintain stability of the product in appropriate container closure systems.
Bioassays are one of the few analytical tools where native proteins can be characterized in vitro, under physiological conditions. They are essential in assuring integrity and functionality of a biological product. Product-specific set of bioanalytical procedures is developed for each product to monitor critical control points.
Our expertise includes the setting of Proliferation, cytotoxic and viral assays. At Rodon these types of bioassays are implemented and carried out on a routine basis in biosafety level 2 laboratory facilities, against suitable controls, and wherever possible International Reference Standards.
In the Proliferation assay the capacity of certain proteins to induce cell division is evaluated in specific mammalian cell type. Alternatively Cytotoxic Assays measure inhibition of proliferation and / or induction of apoptosis. In a Viral Assay a respective mammalian cell line is incubated with the recombinant protein, the recombinant protein transmits protection against viral induced cytolysis.
All bioassays are developed and operated taking into account GLP and regulatory requirements as presented in Pharmacopoeial monographs, ICH, FDA and EMEA guidelines.
Scientific activities in the post-genomics area are extensively focused on identifying and characterising candidate molecules with the potential to benefit and improve the lives of the world´s populations. To effect critical time to market, companies will need to consider their process development strategies early in the drug development cycle, taking the investment risk of increasing their own capacity and resource base or alternatively limiting that risk by outsourcing.
Rodon Biologics has an experienced and qualified team of individuals, resources and proven record in the area of Biologics process development integrated across several areas.
Rodon has extensive experience with both microbial (E.coli, yeast) and mammalian cell culture derived proteins. Using our proprietary and in-licensed technology for expression proteins are rapidly screened in different constructs, to identify the most suitable system, using tightly-regulated inducible promoters for microbial cells. In mammalian cells Rodon provide rapid cell line generation using CHO-S platforms.
Development of a reproducible and productive fermentation process is one of the key stages for the effective manufacture of a recombinant protein. Rodon use their media design and optimisation experience to select appropriate conditions for production activites. The chemically-defined media medium is carefully designed to support high cell densities and expression levels.
For each protein cloned, a careful development program is carried out in order to study in detail, optimal protocols based on the protein characteristics, process steps and conditions. The process optimization is performed in parallel with the DSP process development in order to obtain a global high yielding and high quality process. Process development programme is also cost effective, robust and transferable driven.
Rodon has been developing concepts for obtaining a high throughput approach (e.g. PreDicter plates) to probe for appropriate conditions using different technologies. The most promising conditions are further refined and scaled up to develop an operational process.
At Rodon constant communication and information exchange with the client is promoted as the project progresses to attaining objectives in an efficient and timely manner. Records are meticulously maintained in the appropriate manner ensuring effective management, communication, evaluation of progress and process transfer.