For many companies starting out, the financial risks of building a traditional facility, and the requirements for designing, optimizing and controlling a GMP manufacturing process, are too daunting. A growing number of companies with drugs in early-stage development are working with Xcellerex, a contract manufacturing company and drug developer whose entire platform is based on the FlexFactory Biomanufacturing Platform (FF), which uses disposable process equipment and enclosed, adjustable cleanrooms around equipment. The company also provides engineering, analytical, process control, IT and other expertise in an outsourced package.
At a time when many contract manufacturing organizations lag in their use of novel technology, Xcellerex is clearly marching to the beat of a different drummer. Founder and CTO Parrish Galliher discussed recent developments.
PhM: How has your base grown since you’ve launched, and how many people work on FF as opposed to other businesses?
PG.: We developed FlexFactory back in 2001, and used it internally when the company was launched two years later. We only started marketing it this year. We figured it would take time to gain support for the concept, since pharma is such as conservative industry.
We started the adoption by using the FF internally to provide contract manufacturing services, thus showing customers how it works, as they put drugs in the clinic that were made in the FF, over time the technology would be validated.
Another benefit is that we have been able to debug and “harden” the system. In 2003 we were only at 100-liter scale. In parallel to setting up and running the FF and making drugs in it, we scaled up to 1000-liter working volume, to show that one could use the FF to make enough product to carry a drug all the way to market and make enough for the market itself.
PhM: How many people are working on the FlexFactory portion of the business?
P.G.: We’re 105-110 right now, and will be growing to about 120 people . . . about 50 are dedicated to the contract manufacturing services part of the company, which provides contract services for companies and works on our own drug pipeline. We’re filing our own first IND this quarter. This contract manufacturing services team will be growing to 70 people over the next few months. The rest of the organization manages the engineering for building bioreactors, mixers and FF’s and servicing them. We have about 100 systems out in the world.
PhM: Are you focusing on specific therapeutic categories?
P.G.: We decided to be opportunistic and look selfishly at the drug class that would best demonstrate the benefits of the FF. Two years ago we decided it should be a vaccine. We had no idea at that time that there would be such a revolution occurring in the vaccine industry. We just got lucky.
PhM: Are you just focusing on the front end, in getting processes up the ground? What happens when companies need to move beyond the disposable equipment stage?
P.G.: If you do the math, the 2000-L flex factory is big enough to supply most countries, and we’re working on a 5000-L scale. We don’t see any practical limit to the scale to which we can take the technology.
In parallel, titers are being raised all the time. We have a high throughput screening process optimization team onsite, whose job it is to raise titer up so high that you never have to go beyond the scale at which we’re doing single use manufacturing. We have completed 10 contracts and have three others running right now in which we are raising titers for both companies.
In May, we published results showing how we raised the titer eight-fold for one client, shrinking a 10,000-L stainless steel down to a 1,200-L single-use plant. Suddenly you don’t have to build a $500 million plant but can build a $25 million plant . . . and can have it validated and running within one year vs. 3-6 years.
PhM: Do you collaborate/work with E&C firms?
PG: In 2003 I began visiting all major E&C firms that I used to work with. Back then they didn’t believe that FlexFactory would ever be real. Six years later they are coming to us, we have a teaming agreement with one of the very large companies, and two others that want to go into teaming agreements with us. These are the early adopters. They’re seeing the writing on the wall. The age of stainless steel, traditional, hard piped plants is over, and there’s a move to very flexible, modularized singled use plants and they’d better get on the bandwagon or they’ll be left in the rear view mirror. It has been fun to have them come around full circle. We are already working with them in the U.S. and Europe. They’ll build the building, labs and utilities infrastructure, and Xcellerex will provide the modular production line that will wheel into the building.
PhM: When a client signs up for FlexFactory, what happens next?
PG: Let me talk about Crucell. We build a FF line for them here at Xcellerex. We do all the FAT on it. In parallel, Crucell is auditing our quality systems, and we’re making sure that all the i’s and t’s are ok with them. Once Flex factory is tested by engineering, we will do GMP manufacturing of Crucell’s product here before the FF is transported to Crucell’s facilities. That gives them a 4-6 month jump on clinical trials, which is substantial in this business.
While we produce GMP products for the clinic, they send their manufacturing team here on the floor to be trained on the flex factory. By making their own drug here on their own new FlexFactory, they’ll hit the ground running when the facility arrives. Their clinical group, meanwhile, has picked up a few months by sourcing the clinical material and contracting with us.