Pharmaceutical Manufacturing, February 2015
Considering the capacious amount of time and resources an organization invests in bringing a biologic to market, bioreactor selection is one of the crucial manufacturing decisions for an organization. Unlike small molecule, the cost of production plays a vital role in the pricing of biologics.
Any cost saving measures implemented at the manufacturing stage translates to substantial profits.Single-use bioreactors have come a long way since their inception, when single use was considered revolutionary. Single-use technology has established itself as a popular choice at the preclinical / clinical production stage, and is well on its way on becoming a reliable alternative at the commercial manufacturing stage.
The results from a recently concluded Nice Insight survey quantified the slow induction of single-use bioreactors in the mainstream market. Respondents (biologics outsourcers) were asked about their reactor technology preferences and there was an almost equal preference for the two types of reactors: stainless steel and single-use disposable reactors (68% vs. 67% respectively). There are a few kinks that need to be ironed out, namely the cytotoxicity risks, before single-use reactors can be considered as a standard alternative to the stainless steel reactors. But, given the stringent, methodical and conservative nature of the biopharmaceutical industry, innovative techniques have to pass the rigors of tests, approvals and time before becoming an acceptable standard of operation. The future looks promising for single-use bioreactors, industry analyst have predicted the global single-use bioreactor market to more than double in the next 5 years.
So what exactly does bioreactor preferences mean to outsourcers? Does one select CMOs and realign their bioreactor preferences based on the types of bioreactors offered by the CMO or pick a CMO with equipment that matches their preferences? There are advantages and drawbacks to both options.
Bioreactor selection is a very customized, case-by-case process that is dependent on multiple variables. A CMO may possess state of the art single-use bioreactors, but if the outsourcer requires large 20,000 L stainless steel reactors to complement a similar setup in-house; the state of the art single-use reactors with 250L capacity will not help the outsourcer. However a mix of multiple 2000L single-use stirred tank bioreactors along with some traditional SS reactors will give the outsourcer the confidence in CMO’s ability to fulfill its goals.
On the flipside, what is the significance of bioreactor preferences for a CMO? Understanding bioreactor preferences and staying abreast with the industry demands gives the CMO a competitive advantage over other companies vying for business. CMOs need to make sure they have the right setup along with the technical expertise, know-how and personnel to match the reactors. Having the right mix of reactors (stainless steel, flexible, single-use, different capacities) and the right number of reactors will help CMOs win projects / businesses from sponsors.
2013 to 2015 trends
Year-to-year comparisons revealed that bioreactor preferences have strengthened over the past two years, particularly for single-use disposable technology and the more traditional stainless steel technology. For the single-use disposable reactors there was a 5% point increase in “Strongly Prefer” over the two years whereas the preference for stainless steel technology showed a 6% point increase for “Strongly Prefer” over the same time period.
Industry trends (Pharmaceutical vs. Biotechnology)
Nice Insight also looked at bioreactor preferences from industry’s standpoint. Interestingly, there weren’t any significant differences in reactor technology preferences between the traditional pharmaceutical companies and the biotechnology companies. Infact the preferences were similar except for slight differences in the single-use disposable technology. The Top 2 box preference for stainless steel technology were 69% pharmaceutical vs. 68% biotechnology, for flexible stainless steel technology: 76% pharmaceutical vs. 75% biotechnology and for single-use disposable technology: 66% pharmaceutical vs. 69% biotechnology (a slight difference of 3%).
Popular Single-use Bioreactors
The market is flooded with bioreactors based on multiple technologies. Of these, the wave induced bioreactors and the stirred tank bioreactors are the most popular ones. However, there are a few companies that have bioreactors based on other technologies, namely airlift bioreactors and the vertical wheel stir tank bioreactor.
Over the past decade there have been multiple publications, conference presentations, and promotions for single-use bioreactors. Below we visit some of the established and popular single-use bioreactors in the industry. Please note the list can be exhaustive so we have focused only on a few key popular ones that have a sizeable market share.
GE Healthcare Life Sciences
WAVE Bioreactor System 500/1000
The WAVE bioreactor was a pioneering discovery by Dr. Vijay Singh in the late nineties, it was one of the first successful attempts to move from stainless steel to single-use plastic bags, thus developing a new type of single-use bioreactor. It is available in three different sizes 20/50 L, 200 L and 500/1000 L depending on the needs and requirements. The 200 L and 500/1000 L are the ones designed for cGMP manufacturing. One of the key benefits of this technology is the negligible sheer produced in comparison to the stirred-tank bioreactors making it an ideal bioreactor platform for sheer sensitive cells.
The XDR system is based on similar principles as a conventional stainless steel bioreactor. It is a stirred-tank system based on measures such as sheer, tip speed, power, and fluid velocity.
Available in multiple sizes from bench top lab scale 10L to cGMP commercial manufacturing scale 2000L, the XDR was originally developed for in-house contract manufacturing duty. The design resemblance to a traditional stainless steel reactor helps with the smooth transition from a process development scale to a larger manufacturing scale. The Xcellerex XDR-50 MO fermenter system was designed as a single-use stirred-tank fermenter specifically for microbial culturing. The system has been available for some time now and has proven successful with multiple microbial cell culture lines such as E. coli, Pseudomonas, and Saccharomyces.
HyClone Single-Use Bioreactor
The HyClone SUB system is based on tried and tested stir tank reactor design (STR), emulating the STR scalability and operating parameters, yet retaining the advantage of being a completely disposable device. Each unit comes fully assembled and gamma irradiated, ready to use with a variable speed mixer motor, electrical heating blanket or water jacket, and a control unit for integration with external control system. As per the USP Class VI plastics, it has a disposable S.U.B. BioProcess Container (BPC) bag along with a key element: a plastic (polyethylene) impeller with a bearing/seal assembly linking to an external mixer drive. The S.U.B. features a unique patented mixing system, which provides conventional overhead mixing. It is available in multiple capacities ranging from 50L to 2000L.
HyPerforma Single-Use Bioreactor
The HyPerforma SUB system is based on the HyClone system with some enhanced improvements like a 2:1 turndown ratio that ensures consistent scalability for final production. Like the HyClone, HyPerforma is also available is all sizes ranging from 50L to 2000L.
In the upcoming second part we shall take a look at three other companies that round off the top 5 market players for single-use bioreactors. We shall also share some insights on geographical market preferences for bioreactors and bioreactor preferences based on cell line platforms.
Editor’s Note: This piece, part of a two part series, originally appeared as a sidebar to the cover story, Pharmaceutical Tools of the Trade. In Part 2, That’s Nice researchers take a close look at the remaining three companies that round off the top five market players for single-use bioreactors. That’s Nice will also share its insight on geographical market preferences for bioreactors and bioreactor preferences based on cell line platforms.
The Nice Insight Biomanufacturing Survey was deployed to outsourcing-facing pharmaceutical and biotechnology executives involved in biomanufacturing decisions. The 2014-2015 report includes responses from 440 participants. The survey is comprised of 48 questions and collects data on general outsourcing practices and preferences as well as barriers to strategic partnerships among buyers of outsourced services. Additionally it also collects outsourcing preferences on 11 major CMOs servicing the drug development cycle along with performance metrics used to evaluate CMO project performances. For comparison, the results from this study were viewed along with results from a similar study in 2012-2013.