Biological assays (also called bioassays) are an integral part of the quality assessment required for the manufacturing and marketing of many biological and some non-biological drug products and are often used to assign potency. Bioassays quantify a drug’s ability to modify a biological process, providing insights into its mechanism of action. Bioassays are inherently variable because they rely on biological materials (either the biologically derived drug or the biological substrate [e.g., animals, living cells, or functional complexes of target receptors] on which it might act) that can change over time, thus impacting assay results.

Among many reasons, they can be impacted by:

1. shifts in potency when using different lots of in house standards (Figure 1); or
2. drifts in the potency assignment due to degradation of the drug product or reference standard material (Figure 2); or
3. new lots of critical reagents, new instruments, etc. which can cause shifts in results (Figure 1).

Once a bioassay is implemented for a drug, it is important to monitor its behavior over time. It is imperative to have and use a drug-specific reference standard that has a consistent value that can be used to compare different drug manufacturing lots.

Bioassay Reference Standards

USP offers many product-specific bioassay reference standards (Table 1) that can be used by manufacturers of biologics and other complex molecules to (depending on the molecule and regulatory need) either assign relative potency, detect shifts in potency values when using in-house standards, or to ensure bioassay results do not drift when any critical reagents change. These reference standards are suitable for normalizing potency values across laboratories and instruments, ensuring bioassay staff are well trained, supporting out-of-specification investigations when potency results shift, monitoring a drug, release testing, drug stability studies, and identifying degradation of your drug.