Accelerating the Commercialization of Biosimilar Medicines in India
There is a flourishing biosimilar medicine industry in India focussed on the supply of affordable biologics to the domestic market. Regulators in India have already approved over 50 biosimilar drugs. Companies such as Dr Reddy’s, Biocon and Intas Biopharmaceuticals are internationally recognised brands and play a leading role within this sector. The success that Indian biosimilar companies have experienced within their home territory is leading them to consider tactics for tapping into global markets in North America, Europe and Japan.
The market for biosimilar medicines is highly competitive with many companies chasing the same biosimilar candidate. To be successful, they must reach the market quickly to capture market share and have highly efficient operations that will minimize their operating costs. Biomanufacturing is a crucial capability for biosimilar developers to master if they are to ensure their competitiveness. The uncertainty of the market for biosimilar medicines is forcing firms to consider how they can develop production capacity that can be adapted to fluctuations in market demand. Companies seeking to address markets in territories outside of India must evaluate how they can serve these best. One option is to develop global operations with localized manufacturing sites capable of receiving bioprocesses from process development laboratories through smart process transfers.
Failure to adopt a leading-edge manufacturing capability will result in developers of biosimilar medicines seeing their rivals capture greater market share, compete more effectively on price, make better use of their capital and expand to become global entities more rapidly. Single-use technologies will play a leading role in enabling biosimilar speed-to-clinic and flexible bioprocessing with low upfront costs.
Over 300 delegates met to discuss biosimilar development and production challenges at the Sartorius Stedim India Biopharma Forum and Seminar held in Bangalore, Hyderabad and Mumbai during March 2017. The discussion focussed on a range of technological and service solutions that firms can implement to both accelerate their product to market and improve the efficiency of biosimilar production operations.
Ravin Mehta described how the development of biosimilars could be greatly accelerated if companies adopt the Cellca cell line platform comprising of a CHO DG44 cell line with DHFR expression system, chemically-defined media system and a pre-defined upstream process. By avoiding having to develop their own media, feeds and process, firms can reduce the time it takes to move from DNA to optimized process from 15-18 months to 6-9 months. Mr Mehta presented data verifying the scalability of the cell line platform between 50 L and 1000 L.
In cases where companies have already developed their CHO cell line, delegates heard how companies are optimizing their media and feed strategy using a combination of microbioreactor technology and DoE software to test blends of basal CD CHO media. Upstream process development scientists can then use the media blends that give the highest productivity to optimize their culture process parameters. The final media and feed strategy is determined from spent media analyses.
Terry Gray presented on the analytical services that BioOutsource provides to its biosimilar customers. He highlighted the fact that many firms perform studies to compare their products to the innovator molecules too late in the development cycle. Dr Gray stressed the importance of assessing comparability as early as the cell line development phase and then throughout process development. This avoids any surprises when developers perform biosimilarity studies before seeking regulatory approval.
Biosimilar production processes will deliver product CQAs robustly if firms implement a QbD-approach during development. It is important that firms use scalable process tools to ensure that the design space they have developed in the laboratory will be applicable at the commercial production scale. Henry Weichert explained how multivariate data analysis tools are allowing companies to easily interpret large process data sets from cell cultures and facilitate the comparison of key batch parameters between scales and batches. They allow companies to monitor that their processes are operating within the designated design space. Merck and Biogen Idec have both reported on the use of MVDA tools for real-time process monitoring.
Companies can achieve a greater assurance of biosimilar medicine safety by adopting an appropriate virus clearance strategy. Firms can implement such a strategy by the careful sourcing and testing of raw materials and cell lines, having in-process and release testing, validating a minimum of two orthogonal virus clearance technologies and including at least one robust technology for removing small non-enveloped viruses. Sherri Dolan highlighted that many firms are implementing virus retentive filters into their cell culture media filtration operations to prevent the viral contamination of bioreactors.
|High temperature, short tim||High (> 1000L)||Broad spectrum, highly effective,|
demonstrated at large-scale
Capital costs, utilities, heat labile components,
|UV-C||Variable||Effective for small virus||Footprint and cost could be an issue for large volumes|
|Autoclave||Low||Good for difficult to treat/filter|
liquid eg glucose
|Gamma Irradiation||Limited by shipping|
|Established for other cell culture application (ie serum)||Not suitable for large-scale manufacturing;|
limited efficacy for small viruses
|Very High (> 5000L)||Easily implemented, good for heat sensitive components||Applicable to chemically-defined media|
The dramatic increase in the number of biosimilar companies transferring bulk drug substance (BDS) around complex global manufacturing networks has highlighted the need for safe, reliable and robust packaging solutions that can prevent leaks and product loss. Apala Banerjee described how controlled-rate freezing in single-use bioprocess containers prevents cryo-concentration and protein aggregation while ensuring the security and safety of the BDS.
Developers of biosimilar medicines can access all of these process solutions and services as part of an end-to-end platform from Sartorius Stedim Biotech. The company is unique in its ability to offer these solutions from process development through to commercial manufacturing. Sartorius pioneered the adoption of single-use processing technology within the biomanufacturing industry. To has developed the technology to increase its robustness and ensure assurance of supply to its customers.
Sartorius Integrated Solutions team has worked with companies such as Boehringer Ingelheim, MabPlex, WuXi AppTec, DM Bio, Synthon and Mabion to install hybrid and single-use production capacity allowing them to benefit from access to the most efficient processes with the latest technology and reducing their time to market without compromising on quality.
Dr. Fang Jianmin, President, MabPlex
Sartorius was a key partner in the delivery of MabPlex’s large-scale mammalian cell culture facility for recombinant proteins, mAb and ADC production.
They have helped MabPlex deliver a flexible, state-of-the-art facility that meets the cGMP standards of the USA, EU and China. We look forward to continuing our partnership with Sartorius.