Bound-less Bio-tech

Therapeutics Development

Therapeutics Development

Cell Line / Strain Development

Premas offers microbial, yeast and mammalian platforms to target the expression of therapeutic proteins with varied needs of post-translational modifications and complexity of the protein.

  • Premas combines significant product and process development knowledge to derive the target strain and possible vector combinations. Premas has developed novel signal sequences for periplasmic and extracellular expression (secretary) for therapeutics. We have also performed a number of studies to change Inclusion body expression to periplasmic expression. This has allowed for a Gene to IND of metabolic disorder IND therapeutic protein in 9 months.
  • Yeast Strain, Pichia pastoris and Saccharomyces cerevisiae – the platform technologies with vectors and strains have been used developing certain class of therapeutics in Pichia. On the other hand, targets and critical reagents have been produced using the Saccharomyces strains. Along with more than 20 different vectors for the expression of proteins, these technologies have been highly successful in the expression and supply of proteins.
  • CHO/HEK platforms: Premas has its own platform technology to generate human antibody library. The CHO DG44 cell line works best with our proprietary mammalian expression vectors, which have been designed for high-level stable expression in mammalian hosts. The growth and production properties of our CHO-DG44 cell line are well defined, and the feed strategy has been optimized, allowing for faster and more efficient scale-up to bioreactors. We have observed gram level expression of antibodies per litre level using this cell line and our therapeutic candidates have reached preclinical stage showing very encouraging results.

Process Development

Process development at Premas covers a significant broad spectrum of R&D activities coupled with various input parameters based on in silico analysis, real-world evidence and analytical data. Process development initiates with significant clone development strategies; which then is concomitantly scaled up from shake flasks, to small scale bioreactors (0.5-2.0L) and subsequently into 5L-50L-500L-1100L capacities.

Our upstream process development group develops high cell density E. coli batch, fed-batch and semi-continuous processes for therapeutic recombinant proteins. This group interacts with the strategy and clone development groups from the initiation of the project. This allows for the final objective to clearly evident and visible to the PD group and subsequent downstream and manufacturing groups. COGS, and process simplicity is one of our target hallmarks of working with Premas.

Monoclonal antibodies and mammalian derived proteins, produced from mammalian cell cultures are process developed with similar thoughts. Our approach is flexible, partnership based keeping our clients’ needs. Wave bioreactors (5-25L) and Single Use (1-10L) constitute the first line of process development and scaling up. Gram level yields at the clone /shake flask levels are enhanced with media development, optimizing feed strategies, upstream process development and multi-parametric inputs and controls.

Our downstream process development team has delivered over >650 proteins, of which about 100’s of them have been scale up to > 100L culture volumes. With unit operations scalable to 1000’s of grams of product, harvesting and clarification steps have significant capacities, throughput, and access to multiple options, e.g. high speed continuous centrifuges, concentrations and diafiltrations systems (1000’s of Liters), both cassette and hollow fiber based systems.

Chromatography systems and highly defined process protocols exist at Premas. With the vast experience of over 14 years, Premas has developed unique scale down models (ml to 100’sof L) and processes to rapidly conclude on possible steps, yields and outcomes. (Reference: Application Note: Gene to Phase 1 material in 10 months). Use of multi-modal components and analysis, Premas has been able to deliver some of the significantly challenging products and processes at low COGs.

Further downstream process development is possible at Premas where we develop high protein concentration formulations and lyophilization cycles. Premas has both small and large scale development lyophilizers.

Scale Up and Manufacturing

Premas has multiple lines and suites dedicated to upstream and downstream processing technologies, including fully disposable single-use bioreactor systems. We are capable of meeting our customers’ demands on COGS, flexibility and productivity. Processes transferred from our PD labs seamlessly scale up in our large-scale GMP compliant facility. We have also successfully performed the validation and registration of several 2nd and 3rd generation processes.

Our 24/7 running mode of our processes enable us to design semi-continuous processes, simplified operations and significantly lower COGS processes. We developed different technologies and processes to offer significant advantages to a number of new molecule formats and manufacturing processes. Some of the benefits include a concomitant increase of productivity as well as simplified purification, along with low COGS.

Premas has the capacity to deliver grams to kgs product and drug substance. We have now for a particular product line expanded our capacity to 5kg/week delivery schedules.

This allows Premas to accelerate development of our customer’ product pipeline and enable critical deliveries for their clinical trials in various geographies. We have been audited by various regulatory and regulatory consultants and quality assurance groups of our customers.