CSL Seqirus begins shipping new flu vaccines across the country

Summer’s sweltering heat makes autumn seem far away, but at CSL Seqirus in Holly Springs, N.C., it signals shipping time for the company’s portfolio of 2024-2025 seasonal influenza vaccines. On July 9, the company began shipping its vaccines to healthcare providers across the U.S. before fall’s annual flu vaccination campaigns. 

The Holly Springs site has been hard at work manufacturing influenza vaccines for this season since the World Health Organization announced the recommended influenza vaccine composition for the northern hemisphere on Feb. 23.

During a recent facility tour, the North Carolina Biotechnology Center saw employees taking final steps to prepare and package vaccine doses for shipment. The vaccines are put into syringes under aseptic conditions, placed into cartons for commercial sale, and then stacked on pallets so forklift operators can take them to storage. Most of the production process is automated, but employees provide quality assurance inspections each step of the way.

Keith Kulowiec, executive director of biopharmaceutical product development, has been with the facility since 2011. He works with vaccine development teams in Holly Springs and Melbourne, Australia, CSL’s global headquarters.

“We have an incredibly talented group of scientists and engineers working to improve public health that I am proud to be a part of,” he added. “Even so, it took a lot of effort to get to today’s level.”

Cell-based, egg-embryo and mRNA vaccines

The CSL Seqirus Holly Springs site is one of the largest cell culture-based influenza vaccine producers in the world and the first such U.S. facility. In 2014, the U.S. Food & Drug Administration (FDA) licensed the facility for commercial production of cell-based vaccines.

In a cell-based influenza vaccine, the influenza virus is cultivated in the mammalian cell culture, where the virus replicates and antigens, which promote an immune response, are produced. The antigens are purified from the inactivated virus, combined into a final formulated drug product, sent to the FDA for further testing and approval, and shipped to healthcare providers.

A traditional influenza vaccine uses eggs as part of the manufacturing process. That method is still used, but it requires an enormous number of eggs. “Influenza vaccine manufacturing facilities that use eggs can go through 500 thousand eggs a day,” said Jon Kegerise, who heads up the CSL Seqirus Holly Springs site, which does not use eggs.

More recently, recombinant or mRNA vaccines are in development by multiple manufacturers for seasonal influenza, but none are approved or on the market. The CSL Seqirus Holly Springs site is developing sa-mRNA vaccines and produces cell-based influenza vaccines. The company’s sites in Parkville, Australia, and Liverpool, England, produce egg-based influenza vaccines. CSL Seqirus has built a second cell culture-based facility in Melbourne, Australia, the original home to CSL—which began working on influenza just before the 1918-19 pandemic that killed millions of people worldwide. 

Common illness can prove deadly; vaccination helps

Influenza, with its fever, aches, and chills, may not seem especially serious. Yet each year, it causes significant illness, hospitalizations, and even death. High-risk groups include people over 65 years of age, young children, pregnant women, and people with chronic illnesses. Complications include pneumonia, bronchitis, sinus infections and ear infections.

The U.S. Centers for Disease Control and Prevention (CDC) estimates the following impact of influenza in 2022-2023 in the U.S. alone:

•    31 million people sick with flu
•    14 million visits to a health care provider for flu
•    360,000 hospitalizations for flu
•    21,000 flu deaths

The CDC notes there are many benefits to getting flu vaccinations: reducing the number of people who get the flu, including pregnant people and newborns; reducing illness severity and hospitalizations—and even deaths.

In June, the CDC issued a statement encouraging people 6 months and older, with some exceptions, to get the updated flu vaccine. 

Evolving flu virus, annual vaccine 

Unlike other illnesses we receive vaccinations for, such as polio, measles and mumps, the seasonal influenza virus consists of strains that evolve continually. Each year’s vaccine must be developed anew. “Flu virus strains are like children,” Kulowiec said. “Once you know how one behaves, it changes,” which means the seasonal flu vaccine itself must change as well—and within a very tight timeframe.

The process occurs through a vigorous global surveillance and data review process led by the World Health Organization, which hosts two meetings per year to announce the recommended composition of influenza vaccines for the Northern and Southern Hemisphere seasons. The meeting for the Northern Hemisphere typically takes place in late January or early February, meaning that CSL Seqirus and the small number of other FDA-approved U.S. flu vaccine manufacturers have about six months to complete preparations and ship products. 

CSL Seqirus flu vaccine portfolio

The current vaccine portfolio being shipped includes:

• FLUCELVAX® (Influenza Vaccine), the first and only cell-based influenza vaccine indicated for use in people six months and older.
• FLUAD® (Influenza Vaccine, Adjuvanted), the first and only adjuvanted seasonal influenza vaccine for adults 65 years and older recommended by the CDC's Advisory Committee on Immunization Practices (ACIP) over standard-dose influenza vaccines. It is egg-based and contains MF59® an additional substance, or adjuvant that, when added to a flu vaccine, is designed to strengthen, broaden, and lengthen the immune response. This is important for adults 65 years and older whose immune systems may have a decreased capacity to respond to flu illness or vaccines.
• AFLURIA® (Influenza Vaccine), an egg-based, influenza vaccine approved for use in eligible people six months of age and older.

This year, the company is producing trivalent influenza vaccine (TIV) formulations, in compliance with the FDA’s directive to remove the B/Yamagata strain.

Public-private pandemic partnership

The CSL Seqirus Holly Springs manufacturing facility was born out of a 2009 public-private partnership between Novartis and the federal Biomedical Advanced Research and Development Authority (BARDA), part of the U.S. Department of Health and Human Services, and responsible for pandemic preparedness. In 2014, Novartis divested its vaccine division, which global biotechnology company CSL purchased, resulting in Seqirus in 2015. Seqirus was rebranded as CSL Seqirus in 2022.

The company takes very seriously its role in rapid pandemic response. In 2022, the U.S. government designated the site ‘pandemic ready,’ meaning it was officially recognized as having successfully established domestic manufacturing capability for cell-based seasonal and pandemic influenza vaccines.

In late May, BARDA announced another grant to CSL Seqirus, to provide 4.8 million doses of vaccine for a pandemic response for avian “bird” flu, which recently reappeared in the U.S. and elsewhere. This was the fourth avian influenza pandemic preparedness award CSL Seqirus received from BARDA under a multi-year agreement.

Pandemics are so deadly because they are usually illnesses to which we have little or no immunity. SARS-Co-V2 (COVID) is a good example. Vaccines provide some immunity to newer illnesses such as COVID.

“We can close off one or more lines to produce only the vaccine needed for a pandemic,” said Kegerise, “while still manufacturing the annual influenza vaccine.” Both are vital to overall public health, he emphasized, and to CSL Seqirus’ commitment to BARDA. He also noted that during COVID, supply-chain interruptions caused problems for pharma and other suppliers. “To ensure we are able to meet BARDA’s high standards, we keep all needed materials on hand,” he added.

Delivering on a promise

Kegerise stepped into the Holly Springs site head role in 2023 after 10 years at the facility and in global roles. For him and his colleagues, CSL Seqirus is not just a global enterprise. As he posted on LinkedIn: “We helped CSL Seqirus bring 135 million doses of flu vaccine to the world last year [2022-2023].

“Being able to deliver on a promise to so many people in our community, the nation and the world is an amazing feeling, and I’m excited for what’s to come in the future.”