NIR Spectroscopy Could Improve Flu Vaccine Manufacturing

Researchers at North Carolina State University are using near-infrared (NIR) spectroscopy in hopes of making cell-culture-based flu vaccine manufacturing faster and more efficient. They used an NIR probe to measure the concentration of influenza virus in cells being grown in a bioreactor.

The North Carolina State technique proved to be faster, more accurate, and more consistent than standard methods used to measure viral concentrations in cells, giving the researchers close to real-time data on viral concentrations.

“Getting data that quickly can help in a number of ways,” said John Sheppard, a professor of bioprocessing science at North Carolina State. “It can tell vaccine manufacturers when the optimal time is to harvest the cells. It can help manufacturers develop a feeding strategy to optimize cell and virus growth. It can help detect potential problems with a batch more quickly. It could even allow the process to be partially automated.”

Most flu vaccine manufacturing is done using poultry eggs. However, this approach — first developed in the 1940s — has a number of drawbacks: The resulting vaccine cannot be used by patients with egg allergies; the lengthy manufacturing time and increased risk of mutations makes it more likely that the resulting vaccine won’t match the strains of flu virus facing the public; the vaccine is more susceptible to microbial contamination; and it can’t be manufactured quickly enough to respond to pandemic flu outbreaks.

“Cell-culture-based manufacturing has fewer mutations, fewer allergy problems, and is easier to scale up,” Sheppard said. “But that doesn’t mean that it’s easy. Industry is already transitioning to cell-culture-based vaccine manufacturing, but there are infrastructure and regulatory challenges. We think the use of NIR spectroscopy could help to make cell-culture-based manufacturing more efficient and predictable.”

Before testing their NIR spectroscopy approach to measure viral concentration, the researchers faced a fundamental challenge: The existing standard method for obtaining these measurements was so inaccurate that it couldn’t be used to validate the NIR technique.

“We had to develop an improved manual method — which is significantly more labor intensive — that offered more accurate measurements than the standard lab method,” Sheppard said. “Using the new method, we were able to assess the accuracy of the NIR spectroscopy, and the results were promising.”

At most viral concentrations, the NIR spectroscopy was far more accurate than the traditional standard method; it was also faster. However, at the highest concentrations, accuracy suffered — though it was still at least as accurate as the standard method.

The North Carolina State research is a proof of concept. The researchers hope to incorporate additional data sets to refine the model they use to translate the NIR spectroscopy data. And, eventually, they would like to work with vaccine manufacturers to fine-tune the process.