Antibody production market11/18/2023 ![]() Second, requirement for accelerated timelines to achieve a faster delivery of the pipeline to circumvent competitors or in response to urgent pandemic outbreak needs might also dictate the appropriate process. First, technical restrictions such as support technologies available at the contract manufacturing organization (CMO) or facility design will help to pick the best operational mode. Different considerations must be taken into account. If flexibility would be introduced at this stage, it would help to better satisfy the future needs of the production of the drug. Not only they provide stable expressing cell lines by selecting highly productive clones, but they must also ensure early process transfer. Cell line providers are at the interface of drug development. Saving time, space and money are additional gains to enhanced productivity.ĭespite these great advances in manufacturing, there are still process improvement at early stage, notably, for early production. Interestingly, this hybrid operational mode moderately impacts facility design, as it is based on pre-existing processes rather than implementing completely new technologies. It results in shorten production timelines by reducing process duration or can lead to higher final harvest titer in smaller bioreactors. A recent concept consists in pre-stage perfusion (N–1) which allows for robust accumulation of biomass by cell retention for higher seeding density of bioreactors (N). Most of them are qualified as fed-batch process intensification strategies due to the achievement of high seeding densities. Nevertheless, due to the increasing demand for improved efficiency, alternative fed-batch modes have emerged. In addition, multiple parameters such as basal and feed media components, feeding strategy, temperature, pH or process duration can be optimized to maximize cell culture longevity and increase productivity. It is well recognized for its high mAb yields, its reliability, ease of execution and implementation at the industrial scale. įed-batch mode is a simple production mode in which a basal medium is supplemented with feed solutions containing nutrients to support the production phase. These titers are associated with the most dominant production method for mAbs, the fed-batch mode. Over the last 2 decades, expression of mAbs in CHO has been greatly improved and volumetric titers of 10 g/L in 14–18 days can now be achieved. The preferential mammalian system of expression of biopharmaceuticals are the Chinese Hamster Ovary cells (CHO) for their ability to perform post-translational modifications close to human, its efficient protein folding and its delivery of high productivity. Monoclonal antibodies (mAbs) have benefited most from these continuous efforts to meet increasing market demand and reduce manufacturing costs. Many bioprocess optimization strategies have been explored to increase the volumetric productivity while maintaining low operational complexity. With the advent of unnatural molecules that pose increasing industrial problems as these have unpredictable manufacturability, the protein therapeutics industry must constantly innovate. Since intensified fed-batch could rival the cell-specific productivity of a conventional fed-batch, we developed novel hybrid strategies to either allow for acceptable seeding densities without compromising productivity, or alternatively, to push the productivity the furthest in order to reduce timelines. Both strategies improved titer by 100% in 14 days relative to the standard fed-batch process with moderate and acceptable changes in product quality attributes. ![]() Yet, as intensified fed-batch may not always be possible due to limited facility operational mode, we also separately increased the q P with the addition of specific media additives. To do so, we worked separately on the increase of the IVCD as high seeding fed-batch capacity. While titer is influenced by the biomass (expressed as IVCD), the culture time and the cell-specific productivity ( q P), we changed independently each of these parameters to tune our process strategy towards adapted solutions to individual manufacturing needs. ![]() All manufacturing approaches tend to follow the generally accepted dogma of increasing titer since it directly increases manufacturing output. In the field of therapeutic antibody production, diversification of fed-batch strategies is flourishing in response to the market demand.
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