Novavaxís Robinson: Taking Vaccines to the World
Next Fall, Novavax expects to move to Phase III testing of its seasonal flu vaccine. In the meantime, itís refining a manufacturing process that uses disposable process equipment to minimize risk, cost and plant footprint. VP Jim Robinson discusses the companyís plans.
By Agnes Shanley, Editor in Chief
Some companies have reportedly spent millions of dollars getting lines licensed and through all the regulatory authorities. Carrying on all the work required is a big undertaking for a small company like ours, even when the co-inventor is on your team. Especially since the system is novel, you need to convince people that there is no unknown safety risk.
.PhM: Has FDA weighed in on insect cell expression?JR:
FDA has not yet licensed an insect cell-based product. One of the complications with Cervarix is that it uses a non-aluminum-based adjuvant. The U.S. has not approved non-aluminum-based adjuvants for vaccines, so the European vaccine isn’t approved in the US.
FDA reviewed our files because we’re in the clinic in Phase I and II with a number of products. They seem to be more comfortable with insect cell systems and cell lines because we were not the first and they’ve seen enough clinical data from other studies.
There are differences to our process: GSK used Hi5 cells to make HPV protein VLPs and Protein Sciences use the SF9 cell line to make the HA, where we make three proteins to form a particle. But they’ve also done a lot of safety testing. Once theirs is approved, it helps us quite a bit.
Sometimes it’s good to be second or third.PhM: What are your plans for the facility in Rockville?JR:
We have purchased equipment to scale up to 1000 L, and, ultimately, may double that figure. Our Phase III studies could happen next year, so we need to have our process finalized before that point.
This 1000- or 2000-L process/facility would be able to support and gain us market share over a few years of marketing. Even with a product that is different from others, the vaccine market is a very competitive market, with long-term entrenched players and customer loyalty.
We could produce 10-20 million doses of trivalent influenza (the normal annual flu shot) in that facility, which would allow us to compete until we build a larger facility.
What has sped us up a bit is our international relationships. A number of countries don’t have domestic vaccine supplies and have had difficulties getting vaccines during pandemic flu outbreaks.
We now have the opportunity to work with governments and local players, to get a facility in place and to advance technology overall.
The first such alliance is a joint venture in India with Cadila Pharmaceutical Ltd. They currently have a pharmaceutical plant there but our venture will set up a biotech division.
We’ve already begun to put capacity in place within their existing walls, while they design their long-term, ultimate facility. We are also discussing with the Indian government the possibility of making some H1N1 product locally, using our technology and Xcellerex reactors, and the same equipment that we’d use in the US.
Meanwhile, in Europe, we’ve are in the final stages of licensing our technology to Rovi, a biopharmaceutical company in Spain that has a good collaborative relationship with the government, which would provide loans to support a facility, and tech transfer and do clinical studies in Europe.
Through our U.S. studies, Rovi’s European studies and Cadila’s studies in India, we would be able to build a nice large clinical file in the U.S., Europe and India. This would be useful in proving our process, and enabling us to license it around the world.
However, these global relationships have put more pressure on us to quickly lock down our process. We plan to build the same facility in three places, using identical equipment and process, even the same source of raw materials so that each facility is making exactly the same product. This way, clinical studies will all be comparable and can be put into one file. The simplicity of our process would allow us to do this.PhM: What technologies are you using in this facility?JR:
We’re using Xcellerex’s disposable bioreactor and FlexFactory, which is essentially a small cleanroom that goes around each piece of equipment, separating processes that would normally have to be in separate rooms so that they can go into one room. This makes for a much smaller facility requiring fewer people and having better process control. The FlexFactory goes around all unit operations. We’re also using Xcellerex’s bioreactors and some of their mixing technologies.
After the initial production of VLP’s, we go through two filtration processes, using disposable hollow-fiber filters that are supplied by GE Healthcare. We worked with GE for some time to develop both filtration and chromatography processes.
Downstream, we’ve developed a simulated moving bed (SMB) filtration and chromatography separation system, using technology from Tarpon Biosystems Inc., which further reduces our cost of goods and allows us to shrink the process.
It also reduces the amount of resin and buffer that we use. Since chromatography resin accounts for 40% of our production costs, reducing requirements further reduces our cost of goods. Not only does their process improve speed and efficiency, it helps us save money.
After each batch, using Tarpon’s system, we consume all the useful life of the resin so the separation process essentially becomes disposable. Generally, chromatography is such an expensive process that one would never consider disposing of the resin after only one batch. With Tarpon’s process, you use many small columns many times, so you actually do use the resin’s entire useful life within a batch.