Quality by Design (QbD) principles.

2. Scope

This SOP applies to all activities in the product development lifecycle of sterile injectable formulations including pre-formulation, formulation, container closure selection, and technology transfer stages.

3. Responsibilities

• Formulation Scientist: Initiates risk assessment documentation during formulation and process design.
• Project Manager: Oversees risk management across cross-functional development teams.
• QA Representative: Reviews and ensures that all risk evaluations and mitigation plans are documented and GMP compliant.
• Regulatory Affairs: Ensures risk-related documentation aligns with global regulatory expectations.

4. Accountability

The Head of Product Development is accountable for ensuring that all risks are assessed, recorded, and mitigated effectively before advancing to subsequent development phases.

5. Procedure

5.1 Risk Identification

1. Conduct brainstorming sessions and expert reviews to identify risks at each development phase.
2. Use tools such as:
   • Process Flowcharts
   • Ishikawa (Fishbone) Diagrams
   • Historical Data Review
3. Record each identified risk in the Risk Register (Annexure-1).

5.2 Risk Analysis and Evaluation

1. Evaluate each risk based on:
   • Severity (S): Potential impact if the risk materializes
   • Probability (P): Likelihood of the risk occurring
   • Detectability (D): Ease of detection before occurrence
2. Calculate the Risk Priority Number (RPN): RPN = S × P × D
3. Assign risk levels:
   • RPN < 40 – Low
   • RPN 40–100 – Medium
   • RPN > 100 – High

5.3 Risk Control

1. Determine appropriate control strategies based on risk category:
   • Elimination: Design out the risk
   • Mitigation: Implement checks or process controls
   • Acceptance: Accept if risk is within tolerance
2. Implement Corrective and Preventive Actions (CAPA) for high and medium risks.
3. Document control actions in Risk Mitigation Log (Annexure-2).

5.4 Risk Review and Communication

1. Schedule periodic risk reviews (at major milestones or every 6 months).
2. Update risk registers as needed following:
   • New data availability
   • Change controls
   • Regulatory feedback
3. Ensure all stakeholders are informed through Risk Assessment Summary Reports (Annexure-3).

6. Abbreviations

• SOP: Standard Operating Procedure
• RPN: Risk Priority Number
• CAPA: Corrective and Preventive Action
• QbD: Quality by Design
• ICH: International Council for Harmonisation

7. Documents

1. Risk Register – Annexure-1
2. Risk Mitigation Log – Annexure-2
3. Risk Assessment Summary Report – Annexure-3

8. References

• ICH Q9: Quality Risk Management
• ICH Q8(R2): Pharmaceutical Development
• EU GMP Volume 4 – Annex 20: Quality Risk Management

9. SOP Version

Version: 2.0

10. Approval Section

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

11. Annexures

Annexure-1: Risk Register

Risk ID	Description	Severity	Probability	Detectability	RPN	Category
R001	Container-drug interaction	7	6	4	168	High

Annexure-2: Risk Mitigation Log

Risk ID	Action Taken	Implemented By	Date	Effectiveness Verified
R001	Used alternate low-reactive stopper	Sunita Reddy	02/06/2025	Yes

Annexure-3: Risk Assessment Summary Report

Project Name	IV Paracetamol 500mg
Date	05/06/2025
Prepared By	Rajesh Kumar
Summary	Key formulation and packaging risks identified and mitigated. No critical unresolved risks.

Revision History

Revision Date	Revision No.	Details	Reason	Approved By
12/01/2022	1.0	Initial Release	New SOP	QA Manager
18/06/2025	2.0	Aligned with updated ICH Q9 framework	Annual Review	QA Head