In part one of this biologics series, leading Alcami experts established the biologic challenges resulting from residual DNA. In this second part, we will build upon the fundamentals of bioassays.
Biological assays (bioassays) use biological substrates and entities to determine the critical quality attributes of a drug product. These applications are suitable to both small molecules and large molecules (i.e., biologics). While these assays typically exhibit more variability than chemical-based assays, bioassays provide vital tools in the assessment of product toxicity and potency.
Relative Potency Assays The use of relative potency assays provides an effective means to analyze a qualified reference standard (RS) in parallel with the test sample (TS). Relative potency is derived from a measurement arising from the analysis of dose-response curves of RS and TS. If the RS and TS are biologically similar, it is expected that, at the same concentration or dilution, the TS will exert a biological response in a similar manner as the RS. In the context of bioassays, relative potency assays provide the characterizations of process intermediates, formulations, contaminants, degradation products, standard and reagent qualifications, stability assessments, lot release of drug substance and supportive changes to the product production process.
Quality Control of Bioassays Due to the inherent variability that can arise from assays involving living cells, every effort must be made to identify and control for variables. Through closely monitored cell growth, viability and mycoplasma cell screening coupled with the use of high-quality reagents cell-based assays yield consistent results. In addition, it is essential to follow guidelines from cell culture banks regarding the growth characteristics and nutritional requirements for a variety of cell types. Foremost, subject matter experts must be familiar with the appropriate United States Pharmacopeia (USP) chapters regarding bioassays, i.e., <87>, <88>, <661.2>, <1030>, <1031>, <1032>, <1033>, and <1034>.
Bioactivity of Drug Substances and Products Bioassays provide functionality to the chemical structural analytical approaches. In addition, a cell-based assay can provide a critical need in the characterization of drug substances and products. Not only can these assays provide insight into the functionality of molecules, but also ensure that drug substances and products are in harmony with US Food and Drug Administration (FDA) requirements.
Alcami has a dedicated bioassay group that performs cell-based assays for analytical testing. We have standard operating procedures for cryopreservation of cells, initiation of cell growth from storage, cultivation, and the enumeration of viable/non-viable cells ensures consistency across assays. Our proven approaches to cell-based bioassays ensure that our clients are in position to achieve regulatory compliance.