to all analytical methods developed within the Analytical Method Development (AMD) department, including those for APIs, drug products, excipients, intermediates, and packaging materials.

3. Responsibilities

• AMD Scientist: Identifies and documents potential risks during method development stages.
• Team Lead: Reviews risk scores and proposes mitigation plans.
• Quality Assurance (QA): Ensures that the risk assessment process is aligned with corporate and regulatory guidelines.
• Head – AMD: Approves risk categorization and ensures implementation of mitigation strategies.

4. Accountability

The Head of Analytical Development is accountable for ensuring that risk assessments are completed, documented, and integrated into the AMD strategy for every new method.

5. Procedure

5.1 Planning the Risk Assessment

1. Conduct risk assessments as an integral part of method development planning.
2. Define the goal of the risk assessment, e.g., ensuring method robustness, minimizing instrument downtime, etc.
3. Assemble a cross-functional team including AMD scientists, QA, and where required, formulation development staff.

5.2 Risk Identification

1. Identify potential risks in method development, including:
   • Inadequate method selectivity or sensitivity
   • Unreliable sample preparation steps
   • Non-linear calibration curves
   • Equipment-related limitations
   • Variability in reagents or standards
2. Document the identified risks in Annexure-1: Risk Register.

5.3 Risk Analysis and Scoring

1. Use a quantitative or qualitative scale to assess:
   • Severity (S): Impact on product quality or regulatory compliance
   • Occurrence (O): Probability of risk materializing
   • Detectability (D): Ability to detect the failure before it affects outcomes
2. Calculate Risk Priority Number (RPN): RPN = S × O × D
3. Classify risk as:
   • Low (RPN < 40)
   • Medium (RPN 40–100)
   • High (RPN > 100)

5.4 Risk Evaluation

1. Plot risks on a risk matrix (Annexure-2) to visualize criticality.
2. Focus on high and medium risks for mitigation planning.

5.5 Risk Control and Mitigation

1. Develop action plans for high-risk areas:
   • Method redesign
   • Alternate instruments or procedures
   • Training for staff on specific procedures
   • System suitability criteria reinforcement
2. Record mitigation measures in Annexure-3: Mitigation Plan.

5.6 Documentation and Reporting

1. Prepare a risk assessment summary for inclusion in the Method Development Report.
2. Ensure all risk assessments are filed electronically and backed up.
3. Communicate findings to stakeholders during project meetings.

5.7 Periodic Review of Risks

1. Review risks during each phase of method development (feasibility, optimization, validation).
2. Update scores and mitigation status in the risk register (Annexure-1).

6. Abbreviations

• AMD: Analytical Method Development
• RPN: Risk Priority Number
• QA: Quality Assurance
• ICH: International Council for Harmonisation
• SOP: Standard Operating Procedure

7. Documents

1. Risk Register – Annexure-1
2. Risk Matrix – Annexure-2
3. Mitigation Plan – Annexure-3

8. References

• ICH Q9 – Quality Risk Management
• ICH Q8 – Pharmaceutical Development
• WHO GMP Guidelines – Annex on Quality Risk Management

9. SOP Version

Version: 2.0

10. Approval Section

	Prepared By	Checked By	Approved By
Signature
Date
Name
Designation
Department

11. Annexures

Annexure-1: Risk Register

Risk ID	Description	Severity	Occurrence	Detectability	RPN	Risk Level
RA-001	Low precision due to sample matrix effect	4	5	4	80	Medium
RA-002	Detector saturation for high concentration range	5	3	5	75	Medium

Annexure-2: Risk Matrix

Severity vs. Occurrence	Low	Medium	High
Low	Acceptable	Acceptable	Review
Medium	Acceptable	Review	Mitigate
High	Review	Mitigate	Immediate Action

Annexure-3: Mitigation Plan

Risk ID	Mitigation Measure	Owner	Status
RA-001	Use matrix-matched standards	Sunita Reddy	In Progress
RA-002	Adjust detector gain settings	Rajesh Kumar	Implemented

Revision History:

Revision Date	Revision No.	Details	Reason	Approved By
04/05/2025	2.0	Updated calibration frequency and deviation logging format	Audit compliance