Making the Connection: Sterile Connectors Empower Viral Vaccine Production
March 19, 2020
Vaccines prevent disease by introducing the human immune system to a weakened, killed or subunit of a strain of virus or bacteria. They are formulated to introduce the antigen (an antibody generating substance) and encourage a response that produces antibodies against the disease, thereby creating immunity.
A Brief Vaccine History
In 1796, Edward Jenner was in his apprenticeship as a surgeon/apothecary when smallpox was a devastating, fast-spreading disease. Jenner was intrigued to learn that milkmaids who had contracted cowpox working in dairy farms seemed to be immune to smallpox and theorized that these things were connected. To support his theory, he took pus from a milkmaid infected with cowpox and scratched it into the arm of a child. When the child did not fall ill, the concept of the vaccine was born.
Over time the approach to vaccine production and administration has evolved, with great progress across the 20th century, including the eradication of smallpox in the 1950s. This progress was not entirely without incident (e.g. The Cutter Incident) however the lessons learned from this directly contribute to improvements in safety. Fast-forwarding to present day, vaccines are a cornerstone of public health, and the market has continued to grow. According to a Fortune Business Insights report, the global vaccines market size was worth $41.61 billion in 2018 and is projected to reach $93.08 billion by 2026, exhibiting a CAGR of 10.7% during the forecast period.
The Flu Vaccine
One of the most common viral vaccines, the flu vaccine, including inactivated influenza vaccine (IIV), recombinant influenza vaccine (RIV) or live attenuated influenza vaccine (LAIV), is delivered seasonally to protect the population from long-term illness, or in extreme cases of immature or impaired immune systems, death. The strains in the vaccine are chosen based on research that indicates what flu strains are expected for the upcoming season.
The flu vaccine is made via one of three regulatory approved approaches:
- Egg-based (most common): For inactivated influenza vaccines, the candidate vaccine viruses (CVV) are inactivated using heat or chemicals and the virus hemagglutinin antigen, which triggers the human immune system to create antibodies that target the virus, is purified. For live attenuated influenza vaccine, the CVV are alive but weakened so as not to cause illness and are grown in different chick embryos in series. See more in the video below, featuring Pall’s Kleenpak® Presto genderless connector at 45 seconds.
- Cell-based (gaining traction due to egg allergies): The flu CVV is inoculated in a cell-line (generally mammalian, though various methods exist) to replicate for several days. Just a few weeks ago, Seqirus was awarded the first adjuvanted cell-based flu vaccine approval by the FDA.
- Recombinant (the newest method): The DNA coding for the flu virus antigen is obtained and replicated synthetically by combining with a viral vector such as baculovirus or a plasmid, and placing in a qualified cell line to produce the antigen in bulk.
In each case, once grown, the flu virus, or related antigen is harvested, purified, inactivated and formulated into an injectable or inhalable format. Depending on the strength of the vaccine, adjuvants will be added to increase effectiveness. Stabilizers may also be added to enhance shelf life and stability.
With the rapid emergence of acute viral diseases such as Ebola and Zika viruses, the development of more potent vaccines are required. RNA-based vaccines that use the body’s cells to produce a specific antigen that elicits an immune response, represent a promising alternative due to their high potency, rapid development and potential for low-cost manufacturing.
Challenges in Vaccine Manufacturing
Traditional viral vaccine production is laborious, starting with isolating a target virus strain. If the wrong strain(s) is selected, it will not be efficacious. Even with the right strain, there are challenges based on a virus’ ability to mutate and evolve rapidly. And while adjuvants enhance the immune response, aluminum-based adjuvants cannot be sterile filtered, increasing the need for single-use closed systems to ensure sterility is maintained during production.
Existing vaccine development and commercialization methods can take 12 to 14 years, making time a critical challenge – seasonal or epidemic demands amplify this challenge. Pressures to decrease timeline and cost of vaccine production continue to build, and there is a tremendous global push to make affordable vaccine access a standard.
Recent outbreaks, such as various coronavirus strains (SARS, MERS and COVID-19), various flu viruses and Ebola have highlighted the importance of accelerating the identification, development and commercialization of effective life-saving vaccines. The industry is responding with novel vaccine platforms that accelerate the development timeline to less than one year. Once developed and confirmed as safe and effective the remaining challenge is one of scaling up the process to supply adequate doses to the market.
The Importance of Fluid Paths in Vaccine Production
From upstream to downstream and into final formulation and fill, there are multiple points of fluid transfer in vaccine production. The points of transfer must be sterile and failsafe to avoid lost batches due to contamination and ultimately to ensure patient safety.
At Pall, our next-generation Kleenpak® Presto sterile connectors offer a unique solution to fluid path challenges, especially in single-use closed vaccine production systems. Proven to maintain sterility when connecting two fluid paths, they are commonly used when sterile filtration cannot be done prior to vaccine filling of syringes or vials intended for patient use.
This sterility defense is provided by a polyethersulfone peel strip material that protects each connector end which is integrated on a gamma-irradiated or autoclaved single-use assembly. With an easy-to-use ‘click-pull-twist’ mechanism, each connector end is joined, the protective peel strip removed and the connectors actuated. Intuitive design features visual error-proofing to verify that the product is securely connected and ready for sterile fluid transfer.
While trendier drug products like cell and gene therapies get a lot of media attention, there is still a great deal of innovation in the vaccine space. More than 120 new products are projected to be in development, and manufacturers are looking at ways of improving vaccine manufacturing with a different toolbox for speed and reliability.
Pall Biotech supports drug manufacturers globally with ready-to-use solutions that integrate easily into existing systems and processes, or total solutions with equipment and services that cover your full process. We have also amassed a wealth of data and expertise to optimize the development of a process from research and development through to commercial scale.
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Claire Jarmey-Swan – Global Product Manager, Pall Biotech
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