Identifying and controlling CQAs of the drug product, API, and excipients are essential for ensuring product quality, safety, and efficacy.
1. CQAs of the Drug Product
These attributes affect the therapeutic efficacy, safety, and shelf-life of the final dosage form (tablet, capsule, injectable).
Dissolution Rate/Release Profile:
- Determines bioavailability and efficacy.
- Key factors: API particle size, excipient interactions, dosage form design.
Drug Content and Uniformity:
- Ensures consistent dosing.
- Key factors: Mixing, granulation, equipment precision, excipient quality.
Physical Stability (Appearance, Hardness, Friability):
- Maintains performance and patient acceptability.
- Key factors: Manufacturing processes, binders, lubricants, coatings.
Microbial Limits:
- Prevents harmful contamination.
- Key factors: Sterility, preservatives, handling processes.
2. CQAs of the Drug Substance (API)
The API’s attributes significantly impact drug product performance.
Purity/Impurity Profile:
- Ensures safety and efficacy.
- Key factors: Manufacturing, purification, degradation pathways.
Particle Size and Morphology:
- Influences dissolution, bioavailability, and stability.
- Key factors: Milling, crystallization.
Solubility:
- Affects absorption and bioavailability.
- Key factors: Formulation techniques (solubilization, salt forms).
Moisture Content:
- Prevents degradation, especially for hygroscopic APIs.
- Key factors: Storage, drying processes.
Polymorphism:
- Different crystalline forms impact solubility and stability.
- Key factors: Crystallization conditions, temperature.
3. CQAs of Excipients
Excipients support drug delivery and product performance.
Purity and Quality:
- Prevents harmful impurities.
- Key factors: Sourcing, quality testing.
Particle Size Distribution (PSD):
- Impacts flow, mixing, and compression.
- Key factors: Milling, granulation.
Moisture Content:
- Avoids degradation and instability.
- Key factors: Storage, handling.
Flow Properties:
- Ensures smooth manufacturing processes.
- Key factors: Lubricants, binders.
Compatibility with API:
- Prevents chemical interactions affecting stability or efficacy.
- Key factors: Pre-formulation and compatibility studies.
4. Selecting Excipients for Quality Drug Products
Functionality:
- Select excipients based on their role (binder, disintegrant, lubricant).
- Example: MCC for compressibility and disintegration.
Impact on Bioavailability:
- Enhances solubility and controls release.
- Example: Polysorbate 80 for poorly soluble drugs.
Manufacturing Considerations:
- Must be compatible with production processes.
- Example: Mannitol as a lactose substitute for intolerant patients.
Conclusion
Identifying and controlling CQAs of the drug product, API, and excipients is essential for consistent quality, safety, and efficacy. Careful selection and control of these attributes optimize drug performance and ensure compliance with regulatory standards.
Read also:
- A Brief Discussion on QbD Tools
- CPP and CQA for Tablet Manufacturing
- Product Design and Understanding in QbD
- Risk Assessment for API Properties in Solid Oral Formulation
Resource Person: Moinuddin syed. Ph.D, PMP
 in Formulation Development){kind=link}