Q9, and Q10 standards for pharmaceutical development and GMP compliance.

2. Scope

This SOP is applicable to all sterile injectable formulations developed or manufactured within the facility, including both small molecule drugs and biologics. It covers activities from product development through to commercial production, including changes via lifecycle management.

3. Responsibilities

• Formulation Development Team: Proposes initial CQAs based on formulation and product profile.
• Quality Assurance: Reviews and approves identified CQAs, and ensures ongoing monitoring and documentation.
• Quality Control: Conducts testing to validate CQA parameters.
• Regulatory Affairs: Ensures compliance with guidelines in regulatory submissions.
• Manufacturing: Implements and controls CQAs during routine production.

4. Accountability

The Head of Quality Assurance is accountable for ensuring that appropriate CQAs are defined, monitored, and documented according to applicable guidelines and product requirements.

5. Procedure

5.1 Initial Identification of CQAs

1. Review the Quality Target Product Profile (QTPP) for the sterile injectable product.
2. Analyze formulation components, process characteristics, and product specifications.
3. Use prior knowledge and risk assessment tools (e.g., FMEA, Ishikawa) to determine potential quality attributes that impact safety, efficacy, and stability.
4. Classify the quality attributes into:
   • Physical (e.g., appearance, pH, osmolality)
   • Chemical (e.g., assay, degradation products)
   • Microbiological (e.g., sterility, endotoxins)
   • Functional (e.g., syringe glide force, reconstitution time)
5. Establish the justification for each identified attribute as a CQA or not, based on its impact on product quality and patient safety.

5.2 CQA Risk Assessment

1. Conduct a formal risk assessment meeting with cross-functional team (QA, QC, R&D, Regulatory, Manufacturing).
2. Assign severity, occurrence, and detectability scores for each potential attribute.
3. Calculate risk priority number (RPN) or use qualitative categorization (High/Medium/Low risk).
4. Document risk ranking and identify high-risk attributes as critical.

5.3 Documentation and Approval

1. Prepare a CQA Summary Report that includes:
   • Attribute name
   • Justification for criticality
   • Acceptance criteria
   • Test method
   • Stage of control (in-process or final product)
2. Submit report for QA and Regulatory review and approval.
3. Incorporate approved CQAs into the Product Development Report (PDR), Master Formula Record (MFR), and Control Strategy.

5.4 Monitoring and Reassessment

1. Ensure all CQAs are included in the routine testing plan (in-process and final product stages).
2. Review CQA trends during:
   • Annual Product Quality Review (APQR)
   • Change control evaluations
   • Deviation investigations
3. Update CQA classifications based on process or formulation changes.
4. Initiate change control for any CQA revision and follow appropriate regulatory procedures for notification or filing.

5.5 Integration with Control Strategy

1. Link each CQA with a specific control point or process parameter (CPP).
2. Ensure validated analytical methods are in place for each CQA.
3. Use Statistical Process Control (SPC) and trend analysis tools to monitor consistency.
4. Document all controls in the Validation Master Plan (VMP) and Quality Risk Management Plan (QRMP).

6. Abbreviations

• SOP: Standard Operating Procedure
• CQA: Critical Quality Attribute
• QTPP: Quality Target Product Profile
• FMEA: Failure Mode and Effects Analysis
• RPN: Risk Priority Number
• CPP: Critical Process Parameter
• SPC: Statistical Process Control

7. Documents

1. CQA Risk Assessment Form – Annexure-1
2. CQA Summary Report – Annexure-2
3. CQA Monitoring Log – Annexure-3

8. References

• ICH Q8 (R2) – Pharmaceutical Development
• ICH Q9 – Quality Risk Management
• ICH Q10 – Pharmaceutical Quality System
• WHO TRS 986 – Annex 2: GMP for Pharmaceutical Products

9. SOP Version

Version: 2.0

10. Approval Section

	Prepared By	Checked By	Approved By
Signature
Date
Name
Designation	Formulation Executive	QA Executive	Head QA
Department	R&D	Quality Assurance	Quality Assurance

11. Annexures

Annexure-1: CQA Risk Assessment Form

Attribute	Severity	Occurrence	Detection	RPN	Risk Level
Osmolality	5	3	3	45	Medium

Annexure-2: CQA Summary Report

Attribute	Critical	Test Method	Acceptance Criteria
pH	Yes	pH meter (USP)	4.5 – 7.0
Sterility	Yes	Membrane Filtration	No Growth

Annexure-3: CQA Monitoring Log

Date	Batch No.	CQA	Result	Reviewed By
21/06/2025	INJ2356	pH	6.2	Sunita Reddy
21/06/2025	INJ2356	Sterility	Complies	Sunita Reddy

Revision History:

Revision Date	Revision No.	Revision Details	Reason for Revision	Approved By
01/03/2022	1.0	Initial Issue	New SOP	Head QA
24/06/2025	2.0	Expanded risk analysis and annexure updates	Regulatory Alignment	Head QA