Question 5 of 9 Advanced Concept
What are critical quality attributes in a biologics process?
Short answer
Critical quality attributes are measurable properties that must stay within appropriate limits to help ensure product quality. Depending on the biologic, these can include potency, purity, identity, aggregation, glycosylation or specific impurities. Their criticality depends on risk to safety and efficacy, not simply how easy they are to measure.
Why
Start with the therapeutic product and the patient risk. A quality attribute describes a chemical, physical, biological or microbiological property of the product. It becomes critical when variability in that property could meaningfully affect quality, safety or efficacy, so its desired limit or distribution must be appropriately controlled.
For a monoclonal antibody, examples may include potency, aggregates, glycan profiles, charge variants, host-cell proteins, residual DNA and bioburden, but the actual CQA list is product specific. Teams combine mechanism knowledge, prior platform experience, structure-function studies, clinical relevance and risk assessment to identify attributes worth controlling. They then connect these to process parameters, in-process controls, specifications and analytical methods as appropriate.
A CQA is not the same thing as a critical process parameter. One describes the product and the other a process variable that may affect the product. Formal specifications are related but do not necessarily include every CQA.
Common mistakes
- Calling every measured attribute critical, or confusing the product's CQA with a bioreactor set point
The interviewer might ask next
How would you decide whether a change in glycosylation is clinically relevant?