in compliance with ICH Q2(R1), Q8, WHO TRS, and GMP requirements.

2. Scope

This SOP applies to all method development activities carried out for active pharmaceutical ingredients (APIs), finished dosage forms, excipients, and raw materials in the Analytical Method Development (AMD) department.

3. Responsibilities

• Analytical Scientist: Drafts the method development protocol with technical input and planned experimentation details.
• Team Leader: Reviews the draft protocol for scientific soundness and compliance with project objectives.
• QA: Ensures the protocol includes all mandatory sections and is documented as per QMS guidelines.
• Head – AMD: Approves the final protocol prior to initiation of development studies.

4. Accountability

The Head of Analytical Method Development is accountable for ensuring that all method development activities are initiated only after an approved Method Development Protocol is in place and followed.

5. Procedure

5.1 Protocol Initiation

1. Initiate the protocol upon receipt of a new method development request (analytical R&D form or project kickoff).
2. Assign protocol number as per the defined format: MDP/YY/XXX (where YY = year, XXX = serial number).

5.2 Protocol Structure

1. Prepare the Method Development Protocol using the template outlined in Annexure-1.
2. The protocol must include the following sections:
   • Objective
   • Scope
   • Product and Analyte Information
   • Analytical Target Profile (ATP)
   • Materials and Instruments
   • Proposed Analytical Technique(s)
   • Development Strategy
   • Acceptance Criteria
   • Documentation and Reporting
   • Risk Assessment (if applicable)

5.3 Drafting the Protocol

1. Input detailed product information, chemical structure, solubility, pKa, degradation pathways, and known impurities.
2. Define critical method parameters and their expected impact on performance (CMPs).
3. Include literature summary and justification for method selection or deviation from pharmacopoeial method.
4. Record drafting details in Annexure-2: Protocol Drafting Log.

5.4 Review and Approval

1. Submit draft protocol to Team Lead and QA for review.
2. Incorporate feedback and corrections.
3. Finalize and route for approval by Head – AMD and QA signatories.
4. Attach approval sheet as Annexure-3.

5.5 Protocol Implementation

1. Initiate method development activities only after the protocol has been formally approved and recorded in the protocol tracker log.
2. Ensure that all activities, observations, trials, and deviations are recorded in the Method Development Workbook or ELN.
3. Cross-reference Method Development Protocol in Method Development Report.

5.6 Documentation and Archival

1. Maintain soft and hard copies of the approved protocol under document control.
2. Attach protocol to method development dossier and archive as per QMS.
3. Record protocol status in Annexure-4: Protocol Tracking Sheet.

6. Abbreviations

• MDP: Method Development Protocol
• ATP: Analytical Target Profile
• CMP: Critical Method Parameter
• QA: Quality Assurance
• AMD: Analytical Method Development
• QMS: Quality Management System
• ELN: Electronic Lab Notebook

7. Documents

1. Method Development Protocol Template – Annexure-1
2. Protocol Drafting Log – Annexure-2
3. Protocol Approval Sheet – Annexure-3
4. Protocol Tracking Sheet – Annexure-4

8. References

• ICH Q2(R1) – Validation of Analytical Procedures
• ICH Q8 – Pharmaceutical Development
• ICH Q9 – Quality Risk Management
• WHO TRS 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 Development Protocol Template

Section	Description
Objective	To develop an HPLC method for API assay and related substances
Technique	Reverse-Phase HPLC with UV detection
Strategy	Initial scouting, followed by optimization and forced degradation confirmation

Annexure-2: Protocol Drafting Log

Date	Drafted By	Reviewed By	Version
10/05/2025	Sunita Reddy	Rajesh Kumar	V1.0

Annexure-3: Protocol Approval Sheet

Role	Name	Signature	Date
Prepared By
Checked By
Approved By

Annexure-4: Protocol Tracking Sheet

Protocol No.	Product	Initiation Date	Status	Archived
MDP/25/007	Metformin Tablets	12/05/2025	Approved	Yes

Revision History:

Revision Date	Revision No.	Details	Reason	Approved By
04/05/2025	2.0	Expanded structure and added protocol tracking annexure	Audit compliance