Vaccines have never been a business for the faint of heart. Every facet of the business, from investment to GMP compliance, is fraught with risk. With prices and demand cycling up and down every few years, the market became so unattractive a few years ago that the number of U.S. flu vaccine suppliers dwindled to two. Then came last year’s H1N1 scare, a reminder that flu vaccine manufacturing is inefficient and variable, and the world unprepared for the next flu pandemic.
Novavax is betting on agility and innovation to help it hedge that risk and shore up global vaccine supplies. The company expects to meet the challenges of lower prices and expanding global demand with an insect-cell-based expression system, and an ultra-flexible manufacturing approach.
Most of the company’s management team comes from the world of traditional vaccines--CEO Dr. Rahul Singhvi formerly managed production of varicella vaccine at Merck, while chemical engineer James Robinson, Head of Technical and Quality Operations, spent over 20 years at sanofi pasteur, leading the industrial operations for the only domestic supplier of flu vaccine. But they’ve made a point of taking their company as far as possible from traditional vaccine manufacturing. Their ultimate goal is to license their technology to partners around the world, to ease the global shortage of vaccine. In October, they broke ground in India for a facility being built by their local partner, Cadila, while the following month, Xcellerex began contract production of H1N1 vaccine for Mexico, using Novavax technology.
Novavax is using the Baculovirus Expression Vector System, in which insect cells are cultured and infected with recombinant baculovirus. These cells produce three proteins, hemagglutinin (HA), neuramidase (NA) and matrix protein (M), which form virus-like particles (VLPs) that would offer protection against flu. The company expects to take its VLP-based seasonal flu vaccine into Phase III testing as early as next Fall. Immunogenicity testing is underway in pahse 2 studies, and the company’s scientists project the vaccine to offer special advantage to those over 50 with compromised immunity.
Yields have been shown the expression system be up to 20 times higher (in terms of grams of HA protein per volume) than for traditional methods, while a manufacturing process based on enclosed single-use equipment and downstream separation based on simulated moving bed chromatography, would allow manufacturing plants to be brought onstream in less than a year.
The company built a pilot plant in Rockville, Maryland, last year, at a cost of $5 million and in four months, a fraction of the cost and time required for traditional facilities. A conceptual design for a 75M dose per year plant has been developed for a projected $40M budget. It is now working with partners in India and Spain, and with technology partners that include Xcellerex, GE Healthcare and Tarpon Biosystems to achieve its vision of a single manufacturing process, validated once but replicated around the world.
VP James Robinson recently discussed the company, its plans and strategy.
PhM: What brought you to Novavax?
JR: It was one of those opportunities that only come once in a career. The technology was compelling, but one of the greatest attractions was the opportunity to work with Dr. Gale Smith, who co-invented the BEVS expression system while he was a graduate student in Max Summer’s lab at Texas A&M. I had an opportunity to work with him when I was at sanofi and he was at Protein Sciences Corp. At Novavax, I saw the possibility of taking something that he had invented 25 years ago and applying it to a vaccine that could be used around the world.
PhM: Besides its yield improvement, what else is significant about BEVS?
JR: The nice thing about this expression system is that you’re not actually growing the flu virus, so nobody can catch the virus from working in the production process, and nobody needs to be immunized. It’s a baculovirus itself, essentially a recombinant for of the biological pesticide that we already spray all over our trees and eat in our salads, so it’s very safe to work with. But it’s also a very flexible expression system, and has been used to synthesize over 100 proteins so far.
PhM: Are any other companies working with this expression system?
JR: A number of vaccines are currently being licensed based on baculovirus expression systems: For example, Cervarix, a cervical cancer vaccine developed by GSK, has been licensed in Europe (and now in the U.S.). It uses a different cell line from the one we are using, but the same type of expression system. As GSK and other companies blaze a trail, from a regulatory perspective, it opens up more possibilities for us.
I’m not sure why this whole approval process should take 25 years (the system has been around that long), but it does take time for people to be comfortable and certain that they understand the risks and benefits of a new cell line.
PhM: Are there any technical issues entailed in using this cell line that you wouldn’t run into with traditional systems?
JR: There are published guidelines for using new cell lines, but they are essentially written for mammalian cells. Insects don’t harbor mammalian viruses, so a lot of the guidance that has been written isn’t really relevant for insect cells.
Although insects have viruses, they don’t tend to infect mammalian cell lines, so you don’t risk having some latent virus in your product that could then infect, instead of protect, people. Even though the risk of adventitious viruses is very low with mammalian cells, it still exists, so a great deal of testing is required before you can get them approved.