Novartis recently built a plant for cell-based manufacture of influenza vaccine in Holly Springs, North Carolina. In this
interview, Matthew Stober, global head of technical operations for Novartis, talks about the company's plans for the new facility and new technologies
for vaccine development and manufacturing.
Q:
Novartis recently built a plant for cell-based manufacture of influenza vaccine in Holly Springs, North Carolina. What will
be produced at the facility?
(ADAM GAULT, GETTY IMAGES)
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Stober: Novartis opened its Holly Springs, North Carolina facility in November 2009 in collaboration with the US Department of Health
and Human Services (HHS). The opening of the Holly Springs manufacturing facility is part of our continued commitment to address
urgent healthcare needs for our patients.
The facility has been designed and constructed with the support of the US government to produce seasonal flu cell-culture
vaccine, pre-pandemic [H5N1] and pandemic [H1N1] influenza vaccine. The facility will be ready to respond to an influenza
pandemic as early as 2011 if licensed in an emergency. The plant is expected to be running at full scale and approved for
commercial production in 2013. Additionally, the site will have a fill–finish facility capable of producing both flu and non-flu
products.
Q:
Does Novartis also have an egg-based manufacturing program? If not, why not? If so, what are the challenges/limitations of
producing vaccine in eggs? Are those challenges/limitations alleviated in cell-based systems? Are there challenges inherent
in cell-based manufacture that are not challenges in egg-based systems?
Stober: Yes, Novartis uses both egg and cell-culture technology to produce vaccines in order to provide the greatest amount of vaccine.
While egg-based technology is still the most widely used, cell-culture manufacturing offers several advantages over traditional
egg-based manufacturing, such as the ability to more rapidly respond to time-critical situations, since there is no need for
chicken eggs. Other advantages include more rapid and scalable manufacturing, enhanced consistency and reliability, and cell-culture-derived
vaccines can be administered to patients who are allergic to eggs.
Q:
Please give me a sense of the relative yields of egg- versus cell-based systems.
Stober: Novartis sets high standards for all its products and aims to achieve the highest yield possible using both egg-based and
cell-based technologies. As demonstrated from last year's A(H1N1) pandemic, yields are a biological process and cannot always
be guaranteed. Producing high enough yields was one of the main challenges in developing the H1N1 vaccine because the volume
of vaccine produced depends on how well the virus can replicate. However, cultivating viruses using a cell line offers the
possibility of a more robust virus production and seed-strain development that more closely matches circulating viruses, which
could potentially translate into a more immunogenic and effective response.
Q:
Please give me a sense of the start-up times for egg- versus cell-based paradigms. Scale-up??
Stober: A major advantage of using next-generation influenza manufacturing where eggs are no longer used is that the lead time to
order and take delivery of eggs is eliminated. The Novartis proprietary cell line also allows for manufacturing flexibility.
Because the lead time is eliminated, cell-culture-derived influenza vaccine can be produced more quickly and efficiently in
emergency situations such as pandemics. For example, Novartis was able to produce the first monobulk vaccine for the A(H1N1)
pandemic in only 60 days.
Q:
How do you purify your cell-based vaccines? How does this compare with egg-based purification paradigms?
Stober: The Novartis cell-derived influenza vaccines are purified in a way that is similar to that used for egg- based vaccines, though
there are additional purification steps. For example, host-cell proteins are removed during purification. In egg-based vaccines,
some egg proteins remain in the vaccine.
