department. Proper use of CRS ensures accuracy, traceability, and regulatory compliance of analytical test results.

2. Scope

This procedure is applicable to all activities involving the use of certified reference standards in AMD for chromatographic and spectroscopic techniques, including HPLC, GC, UV, and LC-MS, across pharmaceutical development processes.

3. Responsibilities

• Analyst: Handles CRS preparation, documentation, and usage as per protocol.
• AMD Coordinator: Maintains CRS inventory and coordinates qualification processes.
• QA Representative: Reviews CRS documentation and ensures GMP-compliance during usage and documentation.

4. Accountability

The Head of AMD is accountable for ensuring that certified reference standards are procured, stored, and used in accordance with regulatory requirements and this SOP.

5. Procedure

5.1 Procurement and Receipt

1. Procure certified reference standards from approved vendors or pharmacopoeial sources (e.g., USP, EP, BP).
2. Ensure each CRS is accompanied by a Certificate of Analysis (CoA), traceability certificate, and shipping label.
3. Inspect packaging for integrity and verify label details (batch number, purity, expiry, storage conditions).
4. Record receipt in CRS logbook (Annexure-1) and assign CRS ID number.

5.2 Storage Conditions

1. Store CRS under recommended conditions as per supplier’s CoA (e.g., 2–8°C, -20°C, desiccator).
2. Segregate CRS from working standards and retain in a secure, restricted-access cabinet.
3. Monitor temperature logs daily using calibrated data loggers.

5.3 Qualification of CRS

1. Review CoA for analytical data such as:
   • Assay value and uncertainty
   • Water content
   • Residual solvents
   • Traceability to SI units or national standards
2. Document qualification summary in Annexure-2 template and obtain QA approval before use.

5.4 Preparation of CRS Solutions

1. Calculate quantity based on labeled purity (on anhydrous or as-is basis).
2. Use calibrated balance and Class A volumetric equipment.
3. Record preparation details: analyst name, date, solvent, CRS lot number, and concentration.
4. Label solution with:
   • CRS ID
   • Date of preparation
   • Concentration
   • Expiry date (based on stability data or default 1 month)

5.5 Usage and Traceability

1. Document CRS use in the test method logbook or worksheet with CRS ID and quantity used.
2. Maintain a chain-of-custody record for each use or withdrawal.
3. Ensure CRS is not used beyond expiry or requalification date.

5.6 Disposal of Expired or Unused CRS

1. Mark “EXPIRED” on label and segregate CRS containers for destruction.
2. Follow hazardous waste disposal protocols per site SOPs.
3. Update CRS logbook with disposal date, reason, and authorized personnel signature.

5.7 Handling Deviations

1. Log deviations related to CRS purity mismatch, improper labeling, or out-of-spec assay.
2. Conduct Root Cause Analysis (RCA) and initiate Corrective and Preventive Action (CAPA).
3. Record deviation closure details in Annexure-3.

6. Abbreviations

• CRS: Certified Reference Standard
• CoA: Certificate of Analysis
• RCA: Root Cause Analysis
• CAPA: Corrective and Preventive Action

7. Documents

1. Annexure-1: CRS Inventory Logbook
2. Annexure-2: Qualification Summary Template
3. Annexure-3: CRS Deviation Report

8. References

• ICH Q7 – Good Manufacturing Practice for Active Pharmaceutical Ingredients
• USP General Chapter <11> – Reference Standards
• WHO TRS 996 – Annex 6

9. SOP Version

Version: 2.0

10. Approval Section

	Prepared By	Checked By	Approved By
Signature
Date
Name	Dr. Rachana Mehta	Amit Kapoor	Dr. Krishnan Iyer
Designation	Analytical Chemist	QA Reviewer	Department Head – AMD
Department	Analytical Method Development	Quality Assurance	Analytical Method Development

11. Annexures

Annexure-1: CRS Inventory Logbook

CRS ID	Substance Name	Lot No.	Received Date	Expiry Date	Storage Condition
CRS-2025-01	Paracetamol	PA12458	01/05/2025	01/05/2027	2–8°C

Annexure-2: Qualification Summary Template

Details to include: supplier name, CoA verification, purity value, water content, residual solvents, stability summary, and QA approval.

Annexure-3: CRS Deviation Report

Deviation ID	Description	RCA	CAPA	Status
CRS-DEV-01	Label mismatch on received standard	Supplier error	Vendor notification and corrected labels	Closed

Revision History

Revision Date	Revision No.	Details	Reason	Approved By
01/06/2025	2.0	Updated preparation and qualification steps	Annual SOP Review	Dr. Krishnan Iyer
15/07/2022	1.0	Initial Release	New SOP	QA Head