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
PhM: How are you automating this process?JR:
Xcellerex is also a CRO and CMO and has developed own internal systems for process control, automation and quality. With FlexFactory, we gain all their internal expertise and don’t have to develop our own expertise in automation and engineering.
A lot of people like to invent their own solutions and make their facility unique. The downside is that you’re always revising and retrofitting. By working with Xcellerex, we can use their platform and tie in other unit operations.PhM: Can you share any data on savings from your plant design? JR:
We brought our greenfield Rockville facility on line in four months for $5 million. A production facility of 75M doses per season would coust an estimated $40M. By comparison, Sanofi has built an egg-based facility in the U.S. that will process 600,000 eggs per day to make 100 million doses per year. It will reportedly cost $150 million dollars, excluding utilities and supporting facilities. Novartis is building a $600-million greenfield plant with 50 million dose-per-year capacity in Holly Springs, N.C. So far, it has taken them over four years with costs reportedly approaching a billion dollars.
Working with Jacobs and Xcellerex, we have been able to further shrink our process and increase yields, and the process is much closer to finalization. Equipment can probably be half of what we originally estimated with Jacobs. Each day, costs seem to get lower and yields improve, so the facility could still be smaller and more productive for the same cost. PhM: How will you handle validation? JR:
We are working to design a standard facility that we would build in other countries in collaboration with regional authorities. Our goal is to validate once and duplicate the facility many times. Every facility would use the same scale of bioreactor (using more than one if needed). What we want is a modular suite that has everything for the entire process in one room -one seed train, multiple production reactors and one purification train that allows for flexibility, using the same core technology.PhM: Are you using batch processing exclusively at this point?JR:
We are working with batch processing exclusively, except for the chromatography process, which is almost running continuously, but we haven’t yet defined the start and end of a batch, so it’s not being continuously fed from something upstream.
The idea of continuous process is very interesting because it allows facilities to be even smaller because you don’t have the down time of cleaning between batches--if you can sustain the production process. I’m not sure at this time that our process could be adapted to continuous manufacturing. Further I don’t think it needs to in order to be very competitive with other technologies.
We have a more complex manufacturing system because we have multiple components. First, we need to grow insect cells to high density. In parallel, we grow viruses, then use the viruses to infect insect cells. After they’re infected, cells spend several days make more virus, then there’s a switch in the protein machinery where they stop making viruses and start making virus-like particles (VLPs).
If we could freeze that state and sustain the VLP production period and keep cells living for a very long time in transfected mode, then, in theory, the process could be run continuously.
But our process is already so productive that there is no reason to pursue this route. Perhaps we’d consider it with the second or third generation. There might be benefits, but also complications in how you manage it from a regulatory perspective, .particularly in ensuring the stability of transfection, and we haven’t even started to look at that.
Growing cells at high density, we use a process called bleed and feed, where we grow cells then take them off and grow them again, and keep taking them from one reactor. After a number of these cycles, the bags become more difficult to work with. Debris starts to collect and build up in some of the bag creases. Given these issues, it’s not worth considering continuous when the batch production process works so well.
PhM: What is your timeframe for all these projects?
JR: Our target is to move into Phase III efficacy studies next fall for seasonal flu. We have so far completed Phase I and II studies for H5N1 avian flu and completed Phase II in healthy adults for seasonal flu.
This fall, we will start studying seasonal flu in the elderly, defined as those 50 and over. Unfortunately, after age 50, the human immune system gets less productive. Today’s flu vaccines are estimated to be better than 70% efficacious in healthy adults with good immune systems, but for very young and very old, efficacy drops below 50%. Yet these groups of people are most at risk of infection and mortality from infection.
We believe that our vaccine not only produces antibody responses to hemagglutinin but gives you neuraminidase inhibiting antibody and cellular immunity, we believe that it will be more protective in elderly population, thus more efficacious than today’s egg based products. That study has started, and we’ll expect results soon.
It may turn out that our vaccine does not have confer a great advantage for the healthy adult but offers a strong advantage for immune compromised older populations.
PhM: How does your vaccine compare with commercial vaccines now on the market?