SOP for Developing Analytical Control Strategy in Method Development

Department	Analytical Method Development
SOP No.	SOP/AMD/018/2025
Supersedes	SOP/AMD/018/2022
Page No.	Page 1 of 15
Issue Date	19/05/2025
Effective Date	20/05/2025
Review Date	19/05/2026

1. Purpose

This SOP defines the process for developing an analytical control strategy during the lifecycle of analytical method development. The strategy ensures control over method parameters and analytical performance to deliver reliable, reproducible, and regulatory-compliant results in line with ICH Q8, Q10, and Q14.

2. Scope

This SOP applies to all personnel involved in analytical method development, optimization, validation, transfer, and lifecycle management within the Analytical Method Development (AMD) department.

3. Responsibilities

• Analytical Scientist: Proposes method parameters requiring control and defines limits based on risk and performance.
• Team Lead: Reviews proposed strategy, assesses justifications, and ensures completeness.
• QA: Ensures compliance with documentation practices and control implementation.
• Head – AMD: Approves finalized control strategy and supports its use in validation and transfer activities.

4. Accountability

The Head of AMD is accountable for establishing and maintaining analytical control strategies that ensure method consistency and fitness for use throughout its lifecycle.

5. Procedure

5.1 Identify Method Performance Requirements

1. Define Analytical Target Profile (ATP) (refer to SOP/AMD/015/2025).
2. Identify critical method attributes (CMAs) such as resolution, retention time, %RSD, tailing factor, and linearity.
3. Document in Annexure-1: Method Performance Requirement Log.

5.2 Risk-Based Identification of Critical Method Parameters (CMPs)

1. Based on DoE or prior experience, identify parameters impacting CMAs:
   • Mobile phase pH and composition
   • Flow rate
   • Column type
   • Injection volume
   • Temperature
2. Perform FMEA or Ishikawa analysis for risk prioritization.
3. Summarize results in Annexure-2: CMP Risk Assessment Table.

5.3 Define Acceptable Ranges and Controls

1. Establish acceptable operating ranges for CMPs from:
   • DOE study data
   • Historical batch data
   • System suitability trends
2. Include:
   • System suitability tests
   • Sample preparation checks
   • Equipment calibration and condition checks
3. Record all controls in Annexure-3: Analytical Control Strategy Matrix.

5.4 Establish Monitoring and Review Mechanism

1. Define how each control parameter will be monitored (e.g., through chromatographic system suitability or procedural checklists).
2. Set frequency of monitoring:
   • Per batch for routine tests
   • Monthly or quarterly for trend analysis
3. Assign responsibility for periodic review.

5.5 Documentation and Lifecycle Integration

1. Integrate the control strategy into:
   • Method Development Reports
   • Validation Protocols
   • Analytical Method Transfer Documents
2. Maintain version-controlled records with rationale for all limits.
3. Update strategy based on:
   • OOS investigations
   • Change controls
   • Regulatory updates

6. Abbreviations

• ATP: Analytical Target Profile
• CMP: Critical Method Parameter
• CMA: Critical Method Attribute
• QA: Quality Assurance
• MODR: Method Operable Design Region
• OOS: Out of Specification
• FMEA: Failure Mode and Effects Analysis

7. Documents

1. Method Performance Requirement Log – Annexure-1
2. CMP Risk Assessment Table – Annexure-2
3. Analytical Control Strategy Matrix – Annexure-3

8. References

• ICH Q8(R2) – Pharmaceutical Development
• ICH Q10 – Pharmaceutical Quality System
• ICH Q14 – Analytical Procedure Development
• WHO Technical Report Series 996 – Annex 3

9. SOP Version

Version: 2.0

10. Approval Section

	Prepared By	Checked By	Approved By
Signature
Date
Name
Designation
Department

11. Annexures

Annexure-1: Method Performance Requirement Log

Attribute	Acceptance Criteria	Justification
Resolution	≥ 2.0	To ensure separation from impurity
Retention Time	± 0.2 min	To control variability

Annexure-2: CMP Risk Assessment Table

Parameter	Severity	Occurrence	Detection	Risk Score
pH of Mobile Phase	4	3	2	24

Annexure-3: Analytical Control Strategy Matrix

Control Parameter	Range	Monitoring Method	Action Limit
Column Temperature	30 ± 2°C	System Logger	± 3°C
Mobile Phase Composition	±2% Organic	Batch Record Verification	Deviation triggers OOS review

Revision History:

Revision Date	Revision No.	Details	Reason	Approved By
04/05/2025	2.0	Added Annexure-3 and lifecycle review step	ICH Q14 compliance