CQA

Critical Quality Attribute

ICH Q8(R2) defines a CQA as a physical, chemical, biological, or microbiological property or characteristic that should be within an appropriate limit, range, or distribution to ensure the desired product quality. In practice CQAs are the handful of attributes that genuinely determine whether the product is safe and effective — assay, impurity profile, dissolution, sterility, endotoxin, particulates, potency, aggregation for a biologic.

The discipline is in the word critical. If everything is designated critical, nothing is prioritised and control strategy becomes unmanageable. CQAs are selected by risk assessment against the target product quality profile, weighing the severity of harm if the attribute goes out of range and the likelihood of that happening.

CQAs are the outputs; critical process parameters are the inputs you control to hold them. Establishing which CPPs drive which CQAs is exactly the process understanding Stage 1 validation is meant to produce, and it is what makes a control strategy defensible rather than arbitrary.

• —A CQA is an attribute that must stay within a limit, range, or distribution to ensure product quality (ICH Q8(R2)).
• —Selected by risk assessment against the quality target product profile — severity of harm and likelihood of excursion.
• —CQAs are outputs; CPPs are the inputs controlled to deliver them.
• —Designating too many defeats the purpose — criticality must discriminate.
• —Every CQA should be traceable to a control in the control strategy and to a test or monitoring point.

ICH Q8(R2) Pharmaceutical Development (definition); ICH Q9(R1) Quality Risk Management (the assessment that assigns criticality); ICH Q11 for drug substance; ICH Q6A/Q6B for specifications.