Over the past decade, planned average annual capacity growth in the biopharmaceutical contract manufacturing industry has slowed. This situation reflects both recent market conditions and a shift in investment priorities by biopharmaceutical contract manufacturing organizations.
CMOs have realigned their investment plans to focus on productivity improvements, lower costs, and better asset utilization.
This change in investment policy is documented in HighTech Business Decisions recent report, “Biopharmaceutical Contract Manufacturing: New Participants, Expanded Services and Emerging Markets.” Planned capacity increases, measured by bioreactor volume in liters, for both microbial fermentation and mammalian cell culture have slowed over the last seven years.
In 2005, CMOs expected to add capacity at a rate of 13% per year. Over the subsequent years, expected annual capacity increases have steadily declined. In 2011, CMOs planned to add capacity at a rate of 3% per year.
The CMOs interviewed for this article gave examples of the investments they are making to meet the current and future industry needs.
While new planned expansions have slowed, the CMO industry continues to take advantage of current biotech industry conditions. On July 31, CMC Biologics acquired Xoma’s large-scale manufacturing operations and affiliated assets in Berkeley, CA.
CMC Biologics has taken over the lease of buildings and three 2,750 L stainless steel bioreactors and two purification suites. CMC Biologics has already put a management team in place, and it expects the new facility to be fully operational by the end of this year.
Following the sale of its production facility, Xoma announced that it had entered into an agreement with Boehringer Ingelheim to manufacture gevokizumab, Xoma’s interleukin 1-beta allosteric modulating antibody. Boehringer Ingelheim will manufacture this product for both Xoma and its partner Les Laboratories Servier.
CMC Biologics’ acquisition deal with Xoma is the most recent involving biomanufacturing capacity made by a CMO in the past year and a half. Last year, Boehringer Ingelheim, and Fujifilm, and Gallus BioPharmaceuticals each made major biopharmaceutical manufacturing acquisitions from drug innovator companies.
Boehringer Ingelheim purchased Amgen’s Fremont, CA, biomanufacturing facility. Fujifilm bought Merck & Co.’s contract manufacturing business, and re-named it Fujifilm Diosynth Biotechnologies. Closely following these two acquisitions, Gallus BioPharmaceuticals purchased Centocor’s St. Louis, MO, manufacturing facility in May 2011.
While CMOs continue to add capacity, they are generally doing so in smaller increments, and they are focusing on productivity and quality improvements to meet market demands. Most CMOs interviewed for this article are adding or have added single-use bioreactor capacity. Investing in single-use bioreactors allows for gradual increases in capacity at economically reasonable costs. Both large and small CMOs are installing single-use bioreactors.
For example, Fujifilm Diosynth Biotechnologies is expanding its mammalian cell culture offerings using single-use bioreactors.
“To meet market and customer demand we have significantly expanded our mammalian cell culture offering at both our U.S. and U.K. sites,” said Steve Bagshaw, managing director for the company. “Early this year at our Research Triangle Park site we brought on-line a single-use 1,000 L bioreactor that enables us to offer flexibility of operations to better serve the demands of companies requiring material for pre-clinical studies, early- to mid-phase clinical production, and beyond.”
Fujifilm Diosynth Biotechnologies is also building a cGMP mammalian cell culture facility at its Billingham, U.K., location, which will replicate its RTP mammalian cell culture operations.
In addition to implementing single-use bioreactor capacity, many CMOs are also implementing disposable technologies in downstream purification. The need for downstream improvements results in part from the work that led to higher cell culture titers over the past decade.
In many instances, higher titers caused the biomanufacturing production bottleneck to shift to downstream purification, thereby reducing the overall benefits available from implementing higher titer processes. For example, Boehringer Ingelheim and WuXi AppTec have implemented disposable technologies in both their upstream and downstream processes.
“Boehringer Ingelheim is adding fully disposable processes to our stainless steel capacity, which includes all upstream and downstream process steps,” said Julia Knebel, director marketing and communications, contract manufacturing business, biopharmaceuticals at Boehringer Ingelheim.
“A fully disposable process is one of the technology areas that has been fully evaluated and is no longer a future technology but more a present reality. Alternative technologies to chromatography are also very much in focus. Recent advances in membrane technologies such as membrane absorbers are having an impact throughout the purification process.”
“In the near term, membranes will improve the efficiency and effectiveness of process-based impurity removal such as virus and DNA removal, but in the future, may also impact specific product based impurity removal.”