Published on 07/12/2025
A Complete Guide to Identifying CPPs and CQAs in Pharma for Robust Process Control
Establishing a robust pharmaceutical manufacturing process requires clear identification of Critical Process Parameters (CPPs) and Critical Quality Attributes (CQAs). These elements form the backbone of a well-controlled and validated process. Whether developing a new product or optimizing an existing line, QA, QC, and Validation teams must understand how to define, assess, and control CPPs and CQAs to meet FDA, EMA, and ICH expectations.
This article offers a practical, risk-based, and step-by-step approach to identifying and linking CPPs and CQAs, using ICH Q8 principles, design space concepts, and control strategy development techniques.
What Are CQAs and CPPs?
Critical Quality Attributes (CQAs) are the physical, chemical, biological, or microbiological properties that must be maintained within a specific limit to ensure the desired product quality.
Critical Process Parameters (CPPs) are the operating variables of a process that have a direct impact on one or more CQAs and therefore require monitoring and control to ensure product quality.
These terms are defined in ICH Q8(R2), and are integral to Quality by Design (QbD) strategies and lifecycle validation frameworks.
Step 1: Define the
Begin with outlining the QTPP — a summary of the quality characteristics that ensure the product delivers its intended therapeutic effect.
| QTPP Attribute | Target Specification |
|---|---|
| Dosage Form | Immediate-release tablet |
| Strength | 500 mg |
| Route | Oral |
| Dissolution | >85% in 30 mins |
| Stability | 24 months |
All subsequent CQAs should link logically back to the QTPP.
Step 2: Identify CQAs Based on QTPP and Product Risk
Perform a risk assessment to determine which material attributes and outputs impact patient safety or efficacy. Tools like Ishikawa diagrams and Failure Mode and Effects Analysis (FMEA) are typically used.
Common CQAs in Solid Oral Dosage Forms:
- Assay
- Content uniformity
- Dissolution profile
- Impurities
- Hardness/Friability
- Moisture content
- Microbial limits
Each CQA must be measurable, justifiable, and supported by data from formulation and early process development studies.
Step 3: Perform Process Mapping
Create a high-level flow chart of the manufacturing process, identifying each unit operation (e.g., blending, granulation, drying, compression, coating).
Example Process Steps:
- Dispensing
- Dry blending
- Wet granulation
- Drying
- Milling
- Blending
- Compression
- Coating
Map CQAs to each step to visualize where variability may arise.
Step 4: Link Process Parameters to CQAs
Identify the process parameters that can affect the CQAs. Assess each for:
- Severity of impact
- Probability of failure
- Detectability
This analysis leads to categorizing parameters as critical, key, or non-critical.
Example FMEA for CPP Identification:
| Process Step | Parameter | CQA Impacted | RPN | CPP? |
|---|---|---|---|---|
| Granulation | Binder Addition Rate | Content Uniformity | 180 | Yes |
| Drying | Drying Temperature | Moisture Content | 150 | Yes |
| Compression | Precompression Force | Hardness | 80 | No |
Any parameter with a significant and direct influence on one or more CQAs should be labeled a CPP.
Step 5: Establish Acceptable Ranges and Controls
Define set points and operating ranges for each CPP through experimentation, DOE (Design of Experiments), or scale-up studies. Implement monitoring plans accordingly.
| CPP | Target | Acceptable Range |
|---|---|---|
| Granulation Time | 8 min | 6–10 min |
| Impeller Speed | 300 rpm | 250–350 rpm |
| Drying Temp | 60°C | 55–65°C |
Each range must be justified with data and documented in the Validation Protocol and Control Strategy.
Step 6: Validate and Monitor CPPs
Validation studies must confirm that controlling the CPPs within defined ranges consistently yields product within CQA specifications.
Post-validation, use SPC tools such as control charts and trend analysis to ensure ongoing control. Set alert/action limits based on historical variability and batch records.
Step 7: Integrate into Control Strategy
All identified CPPs and CQAs must be included in your pharmaceutical control strategy, which should be reviewed and approved as part of the Validation Master Plan (VMP).
- CPPs → Controlled via in-line sensors, alarms, interlocks
- CQAs → Verified via in-process and release testing
- Deviations → Tracked through CAPA and deviation systems
Leverage PharmaGMP.in and PharmaSOP.in for downloadable risk assessment templates and SOPs.
Conclusion
The identification and control of CPPs and CQAs form the foundation of any robust, compliant, and efficient pharmaceutical process. By applying structured risk assessments, linking to QTPP, and validating operational controls, manufacturers can ensure process predictability, minimize deviations, and meet global regulatory standards.
Explore additional case studies and real-world applications at ClinicalStudies.in and regulatory strategy insights at PharmaRegulatory.in.