Alberta Fermentation Plant Giving Industry A Helping Hand

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Compiled by Shawn Lawrence

More than 20 years since it was established, the Alberta Research Council’s fermentation pilot plant has remained the largest publicly owned biotechnology fermentation and processing facility in Canada, utilized by organizations ranging from small businesses to large multinational corporations and governments.

The facility’s end goal is to effect technology transfer that contributes to Alberta’s economy and quality of life.

Unsurpassed in North America for scale and versatility, the facility provides crucial services like contract fermentation process development, scale-up and optimization. Additionally, many types of fermentation products: enzymes, proteins expressed in recombinant systems, animal vaccines and other veterinary health products, pharmaceutical intermediates, agricultural products, specialty chemicals, exocellular polymers, and advanced biomaterials have been scaled up here.

Often, technology must be transferred from basic and applied research to facilities for further product development. Piloting services are like an initial step to developing the process, building up a population of organisms through several stages to the size necessary while obtaining data for engineering a larger unit.

This month Biotechnology Focus asked Alberta Research Council chief fermentation scientist Janet Marowitch for her thoughts on the value the ARC fermentation pilot plant provides to the industry.

Q: What makes the facility unique from other fermentation plants in Canada?

Janet Marowitch: We have a unique collaborative approach to biotech and life sciences. ARC is a multi-disciplinary organization providing a bridge from the lab to the marketplace, and we’re here to strengthen our clients’ competitiveness and Alberta’s economy. The facility is unique because of its scale and versatility. We can run a number of processes concurrently and different types of processes because we can interchangeably connect tanks together. Many facilities have dedicated inoculum trains where they have to run processes in a certain way. For example, they can only have a 1% inoculum train or a 10% inoculum train, or they can only go from tank A to tank B, whereas because of the way the facility is organized we have a great deal of flexibility and versatility in how we can run processes. Our primary focus is microbial fermentation, although we can do cell culture as well. We are experienced with more than 50 different species of micro-organisms and can develop a procedure for bacterial, yeast, fungal, algae, recombinant or insect cell culture expression system. Scale-up and manufacturing is possible from shaker-flask to 10,000L.

Q: Are there other facilities like yours in Canada?

JM: We are the only one of our scale and size, which provides our clients with an economical way to scale up. Also, with ARC as a whole, our clients have access to a broad and multi-disciplinary range of expertise and knowledge. They have access to one million square feet of specialized bench scale labs and pilot scale facilities. Our clients and partners come to ARC to accelerate the development of their products, processes and services, getting them to market faster and smarter.

Q: As a fee for service facility, are you considered a contract fermentation facility?

JM: I would say we are more than that and our goal’s are a little different. Our mandate is to help identify leading edge research and assist to develop it so that it can be deployed for the betterment of the economy for the province of Alberta. There is a lot of money going into the development of new technology, not only in Alberta but in other places. The facility is involved in taking that technology, developing it, testing it to see if it is of merit and then seeing that it is actually deployed. The infrastructure which we have is extremely expensive and may be beyond the resources a lot of these individual companies have or that they could invest in particularly before they know that one, they have a workable product and two that product is going to be commercially viable. That really what the facility was set up for 20 years ago.

Q: Why do Canadian biotechnology companies need a facility such as this?

JM: We are helping companies who want to advance their technology from bench to commercial scale. The facility allows research to be developed and its commercial potential tested without individual companies having to build expensive infrastructure. We give companies access to infrastructure and equipment that they would not normally have or the resources to build. It allows us to help deploy leading edge technologies.

Q: How do you design the fermentation process to fit the client’s need?

JM: The baseline process comes from the group we’re working with and then it’s just a matter of working with that organism to determine how best to get it to do what it is you want. That’s just experimentation in the plant. We can do that in flasks, or we can do that in 20 L fermentors. There’s a lot of work that goes into figuring out how to get organisms to produce what you want them to produce, grow how you want them to grow and that takes experimentation, and that’s one of things the facility is designed to do.

Q: How long does it take to establish a fermentation process, optimize it and then scale it?

JM: If you’re starting from shaker flasks, it does take time and that’s not always understood. That’s one of my challenges is making sure people understand the time and the cost involved in doing that. The time required depends a lot on the quality of the information you have to start with. The development processes can be fairly short or it can be quite lengthy, anywhere from six months to five years. One of the processes I worked on, for example, transferred in at shake flask scale. We spent four months doing 20-litre work and scaled it to 150-litres, and spent another two months optimizing at that scale. The company then spent several months testing the material produced. We then scaled the process to 1000L and produced material for pre-clinical testing. We then took the information from the 1000-litre and transferred it to a cGMP facility. And so they were able to get from shaker flasks to a cGMP facility within 12 months, which is actually quite a rapid development. It doesn’t always work that way. It depends on the process, what it is, how defined it is, and it also depends on what your targets for product levels are. Usually what you will do if you’re trying to track development is you develop a baseline process, use it to get material out and get it tested, and then you go back and develop it to make it commercially viable and optimize the process.

Q: The sectors you serve include energy, life sciences, agriculture, environment, forestry and manufacturing. How does fermentation play a role in each of these sectors?

JM: Fermentation has applications that can make a difference in many areas, including impacts on people and our quality of life. We make soil inoculants to improve plant growth. We make feed additives to improve feed efficiency and health of livestock. We make nutritional and nutraceutical products, which can benefit either human or animal health. We make raw materials or active ingredients for therapeutics or medical devices. We make materials used in diagnostic kits; we have made bio-plastics and bio- materials and bio-pesticides. We make platform chemicals, such as organic acids so there is a wide range of applications for this technology.

Q: In which area does fermentation have its greatest potential?

JM: Fermentation has applications that can make a difference in so many different areas and industrial sectors, with the end result of improving our quality of life, the environment, our health. Through fermentation you can increase the quality of some products and you can also decrease the environmental costs of some products or activities. Essentially you can make a better quality product that’s safer, free of contaminants and pure.

Q: Have there been any success stories of a company using your fermentation services?

JM: Yes, for example, a number of years ago we helped a company get to commercial scale and production on this nutritional compound. It’s a nice example on a nutritional compound, and it’s a good example in a number of ways. The company wanted to make a compound, you could get that compound from fish but the problem with getting it from fish is you might have contamination from the fish, you also get a complex compound out, fish oil is a combination of different oils and if you want to take that oil and use it, it might have some attributes that you want, and some that you don’t want like EPA. For infant formula you want DHA and ARA, you don’t want EPA, because EPA is not in breast milk. So you can make these compounds, and they come from algae, the only reason fish has these is because they eat algae, rather than extract the oil from the fish you can take the algae that have the specific oils that you want, the specific Omega 3 oils and Omega 6 oils, and you can grow the individual algae required to for those compounds and then extract those oils. It was a neat project for me because I worked on it for quite sometime, and that company is now commercially successful and has product in 60 countries all over the world. Basically what happened is they had a process that was running at a small scale. They came to us. We did the initial scale up, after scaling it to 10,000 litres, we transferred it to a larger facility that they were working in, they grew it in a larger facility with a larger commercial manufacturer for a number of years, they then bought and built their own facility and they’re now making that commercially. So that’s the idea of this plant is that we can allow people who have this working at a small scale to come test out their technology, make sure that it works, produce material which they can test, and then that will help them produce these products and deploy the technology. Basically we’re turning research into useful and beneficial products.

Q: Has the facility fulfilled its mandate?

JM: Yes. Our mandate is to diversify the economy of Alberta, and our strategy to that end is to assist companies in the developing and deploying technology. Contract fermentation is a very challenging business. It’s challenging to make money at. That’s one reason it’s very important to have it in public ownership. We’re not here to make money, we do want it to pay its way, but this is something we can offer to allow people to get their technology out there without them having to build their own infrastructure or having to pay large dollars. What we’re doing is trying to develop and deploy new fermentation technology, and I think we have been successful in doing that.