Buffers in Biomanufacturing

The complexity and criticality of buffer preparation have grown of late for several reasons. Advances in product offerings, bioprocessing materials, process technologies and facility design have increased the number of factors to be considered. For example, biopharmaceuticals have evolved from classical protein biologicals and vaccines to a diverse number of products and therapeutics such as mRNA vaccines and CGT therapies1. Downstream consequences of increased upstream volumetric productivity have also contributed to a demand for robust and economical buffer preparation.

The buffers and process liquids employed provide physicochemical functions in, e.g., pH maintenance and chromatography, and such biological functions as cofactors for enzymatic activity and nutrients for cell and tissue maintenance. They are used in pharmaceutical manufacturing from product development to fill-finish, can contain such special components as organic solvents, and can have such special formulation demands as sterility.

Buffers are applied throughout the processing train, including biological sample reception, upstream and downstream processing, resins storage, and as excipients in drug product. This determines such considerations as quality level, risks regarding safety and performance, and regulatory compliance. For example, buffers used in the manufacturing of a biotech product, upstream pharmaceutical operations, or as an excipient in a drug product, will require distinct assessments and controls.