stability samples tested without compromising scientific validity, in accordance with ICH Q1D guidelines.

2. Scope

This SOP is applicable to the Analytical Method Development (AMD) department during the design, execution, and validation of stability studies for drug substances and drug products. It covers both new drug development and post-approval changes.

3. Responsibilities

• Stability Coordinator: Proposes bracketing/matrixing designs and maintains the master stability protocol.
• Analytical Scientist: Executes reduced testing strategy and performs data interpretation.
• QA Officer: Verifies that designs are statistically and scientifically justified.
• Head – AMD: Approves the application of bracketing/matrixing approaches in study design.

4. Accountability

The Head of AMD is accountable for ensuring that bracketing and matrixing designs meet regulatory requirements, and that adequate justification and documentation support the reduced testing model.

5. Procedure

5.1 Definitions

1. Bracketing: A design in which only samples on the extremes (e.g., highest and lowest strengths) are tested at all time points, assuming stability of intermediate levels.
2. Matrixing: A design in which a subset of the total number of samples is tested at any specific time point while all combinations are tested over the entire study duration.

5.2 Design Justification

1. Justify the use of bracketing/matrixing based on:
   • Similarity in formulation and packaging
   • Prior stability data
   • Strengths and batch sizes
2. Prepare justification memo reviewed by QA (Annexure-1).

5.3 Protocol Design

1. Draft a stability study protocol incorporating:
   • Number of batches and configurations
   • Time points and conditions (e.g., 25°C/60% RH, 40°C/75% RH)
   • Matrixed or bracketed sample schedule (Annexure-2)
2. Obtain QA and regulatory approvals before initiation.

5.4 Sample Management and Labeling

1. Label samples with unique identification codes indicating batch, strength, packaging, and time point.
2. Store unused configurations in reserve under defined stability conditions.

5.5 Analytical Evaluation

1. Perform analysis as per standard or validated test procedures.
2. Compare results of bracketed samples to ensure intermediate strength assumptions hold.
3. Document results in Annexure-3: Stability Summary Report.

5.6 Data Review and Interpretation

1. Ensure matrixed data across different batches and configurations are within acceptance criteria.
2. If variation is observed outside bracketed limits, perform full testing.
3. Justify continued use of design in final stability report.

6. Abbreviations

• AMD: Analytical Method Development
• QA: Quality Assurance
• SOP: Standard Operating Procedure
• RH: Relative Humidity
• ICH: International Council for Harmonisation

7. Documents

1. Design Justification Memo – Annexure-1
2. Stability Protocol Matrix – Annexure-2
3. Stability Summary Report – Annexure-3

8. References

• ICH Q1D – Bracketing and Matrixing Designs for Stability Testing of New Drug Substances and Products
• ICH Q1A(R2) – Stability Testing of New Drug Substances and Products

9. SOP Version

Version: 2.0

10. Approval Section

	Prepared By	Checked By	Approved By
Signature
Date
Name
Designation
Department

11. Annexures

Annexure-1: Design Justification Memo

Study Title	Stability Study for XYZ Tablet
Design Applied	Bracketing
Justification	Formulations identical across strengths, only API quantity varies.
Approved By	QA Head

Annexure-2: Stability Protocol Matrix

Strength	Batch	1M	3M	6M	9M	12M
50 mg	B01	X	—	X	—	X
100 mg	B02	—	X	—	X	—

Annexure-3: Stability Summary Report

Time Point	Strength	Assay (%)	Degradation (%)	Status
6M	50 mg	98.9	1.1	Pass
6M	100 mg	99.1	0.9	Pass

Revision History:

Revision Date	Revision No.	Details	Reason	Approved By
04/05/2025	2.0	Incorporated ICH Q1D principles and added annexure templates	Regulatory implementation