To make an effective vaccine, a bioprocessor needs to know exactly what is being made.

“The difficulty of characterizing complex biological products makes it especially challenging to ensure that they can be manufactured in a consistent and predictable way,” as noted recently by Darón Freedberg, PhD, research chemist at the FDA’s Center for Biologics Evaluation and Research. “The risk of manufacturing inconsistencies is especially high for novel products, since traditional testing technology might not be able to identify subtle and unanticipated variabilities.”

Freedberg and his colleagues study vaccines composed of pathogenic bacteria encapsulated in polysaccharides. Here, even small variations in the polysaccharides can impact the effect of a vaccine. As Freedberg wrote: “In many cases, polysaccharides differing subtly in composition show significant immunological differences.”

Advanced forms of NMR

So, Freedberg used advanced forms of nuclear magnetic resonance (NMR) spectroscopy to analyze the atomic structure of the polysaccharides. In one approach, the scientists analyzed the structure of polysaccharides on E. coli.

As Freedberg explained: “This method can potentially be used to delineate polysaccharide-antibody interactions and lead to a better understanding of what structures are critical to effective immunogenicity by correlating this information with readily available immunological data.”

Plus, Freedberg and his colleagues studied the three-dimensional structure of repeating units in these polysaccharides. Here, the scientists used various forms of NMR, including residual dipolar coupling, nuclear relaxation and relaxation-dispersion, nuclear Overhauser effects, and other methods. Then, this information can be used in computational models that simulate and analyze the complete polysaccharides.

As Freedberg emphasized, studies like these “enable the FDA and the pharmaceutical industry to ensure that polysaccharide and polysaccharide conjugate vaccines meet regulatory requirements for safety and effectiveness.”

So, when it comes to making vaccines, even the smallest details—from the active molecules to the delivery device—must be analyzed and replicated consistently in manufacturing.

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