CMC & ManufacturingLast reviewed April 2026

Critical Process Parameter(CPP)

A process parameter whose variability has an impact on a Critical Quality Attribute and therefore must be monitored or controlled to ensure product quality.

Usage Examples

Mixing time and impeller speed were identified as CPPs for content uniformity of the blend.
The Design Space for the granulation step covered three interacting CPPs: water amount, spray rate, and drying temperature.
A deviation outside the CPP range triggered a formal investigation and batch quarantine.

What is CPP?

A Critical Process Parameter (CPP) is an input or condition in the manufacturing process whose variability materially impacts one or more Critical Quality Attributes (CQAs) of the drug substance or product. CPPs are identified through Design of Experiments (DoE) and process risk assessment, establishing quantitative relationships between parameter ranges and CQA outcomes.

Typical CPPs include temperature, pH, mixing time and intensity, reaction time, feed rates, tablet compression force, spray rate in granulation, and centrifugation speed. Each CPP has a Normal Operating Range (NOR) where the process routinely runs, a Proven Acceptable Range (PAR) demonstrated to produce in-specification product, and — in a mature QbD submission — a Design Space representing the multi-parameter region of acceptable operation.

CPPs are the operational control targets in the manufacturing process and appear in Module 3.2.P.3.3 (manufacturing process description) and Module 3.2.P.3.4 (controls of critical steps and intermediates) of an eCTD submission. Strong CPP identification reduces deviation rates, batch failures, and regulatory questions during CMC review.

Regulatory Context

This term appears most often in cmc & manufacturing workflows where submission quality, regulatory evidence, and audit readiness depend on consistent language. It is commonly referenced alongside ICH Q8, ICH Q9, ICH Q10.

FDAICHHealth Canada

When This Matters

Mixing time and impeller speed were identified as CPPs for content uniformity of the blend.
The Design Space for the granulation step covered three interacting CPPs: water amount, spray rate, and drying temperature.
A deviation outside the CPP range triggered a formal investigation and batch quarantine.

Common Mistakes

Failing to align CMC change narratives with current CFR/ICH expectations.
Submitting incomplete control strategy documentation.
Separating manufacturing and regulatory review cycles too late in execution.

Related Regulations

ICH Q8ICH Q9ICH Q10

Frequently Asked Questions

Through process risk assessment and Design of Experiments (DoE). The team identifies all process parameters, assesses potential impact on CQAs, and conducts studies to quantify the parameter-attribute relationships. Parameters with demonstrated impact on CQAs within the studied range become CPPs.

NOR is the narrow range where the process routinely runs during commercial manufacture — day-to-day operations stay within NOR. PAR is the broader range demonstrated through studies to produce in-specification product. PAR provides regulatory flexibility; NOR is the operational target.

Yes. A parameter initially classified as non-critical can be reclassified based on new knowledge — a deviation investigation revealing impact, stability data, or scale-up studies. Reclassification as a CPP typically requires a formal change control and CMC regulatory action proportional to the impact.