management of reference standards is critical to ensure accuracy, traceability, and regulatory compliance.

2. Scope

This SOP is applicable to all reference standards used in the development and validation of analytical methods, including pharmacopeial, in-house, and working standards utilized within the AMD department.

3. Responsibilities

• Analyst: Requests reference standards and ensures appropriate handling during analytical use.
• AMD Documentation Officer: Maintains inventory records, logbooks, and qualification documents.
• Section Head: Verifies suitability, approves use, and ensures standards are within validity period.
• QA: Audits compliance with procedures and ensures traceability of all reference standards.

4. Accountability

The Head of Analytical Method Development is accountable for ensuring that reference standards are appropriately procured, qualified, stored, and used in accordance with applicable regulatory and internal requirements.

5. Procedure

5.1 Procurement of Reference Standards

1. Obtain pharmacopeial standards (e.g., USP, EP, IP) from official agencies only.
2. In-house standards must be synthesized or isolated under GMP conditions with full characterization data.
3. Secondary working standards should be qualified against primary reference standards.
4. All reference standards must be accompanied by a Certificate of Analysis (CoA), characterization report, and MSDS.

5.2 Receipt and Logging

1. Upon receipt, inspect the reference standard for labeling, damage, and physical appearance.
2. Enter the details in the Reference Standard Receipt Log (Annexure-1) including source, batch number, potency, and expiry date.
3. Assign a unique identification number (e.g., RS/AMD/001/2025) for traceability.

5.3 Qualification of Working Standards

1. Compare working standard purity and response factor with a qualified primary standard.
2. Perform at least three replicate analyses to confirm assay reproducibility.
3. Document qualification results using the format provided in Annexure-2.
4. Only qualified and approved working standards should be used for routine AMD activities.

5.4 Labeling Requirements

Each vial or container must be labeled with the following:

• Reference ID
• Name of compound
• Purity or potency (%)
• Storage condition
• Date of receipt
• Expiry or requalification date

5.5 Storage Conditions

1. Store standards in a designated refrigerator or controlled room with 2–8°C or ambient temperature as specified.
2. Use desiccators or sealed containers to protect from moisture, light, or air exposure where applicable.
3. Temperature monitoring and access control should be implemented as per Annexure-3.

5.6 Usage Guidelines

1. Use reference standards only within their validity period.
2. Record each usage in the Reference Standard Usage Log (Annexure-4) including analyst name, date, quantity used, and purpose.
3. Avoid multiple freeze-thaw cycles and always use calibrated weighing balances.

5.7 Requalification and Disposal

1. Requalify standards nearing expiry based on stability data or analytical comparison.
2. If found unsuitable or expired, document and dispose as per SOP for hazardous waste disposal.
3. Archive all records and CoAs for minimum 5 years.

6. Abbreviations

• RS: Reference Standard
• WS: Working Standard
• CoA: Certificate of Analysis
• MSDS: Material Safety Data Sheet
• GMP: Good Manufacturing Practice

7. Documents

1. Annexure-1: Reference Standard Receipt Log
2. Annexure-2: Working Standard Qualification Report
3. Annexure-3: Storage Temperature Monitoring Log
4. Annexure-4: Reference Standard Usage Log

8. References

• ICH Q7 – Good Manufacturing Practice for Active Pharmaceutical Ingredients
• USP General Chapter <1225> – Validation of Compendial Methods
• WHO Technical Report Series No. 943

9. SOP Version

Version: 2.0

10. Approval Section

	Prepared By	Checked By	Approved By
Signature
Date
Name	Akshay Mehra	Anita Joshi	Dr. Rakesh Rawat
Designation	Analyst – AMD	QA Reviewer	Head – Analytical Method Development
Department	Analytical Method Development	Quality Assurance	Analytical Method Development

11. Annexures

Annexure-1: Reference Standard Receipt Log

Date	Reference ID	Name	Purity	Source	Expiry	Status
29/05/2025	RS/AMD/003/2025	Paracetamol	99.5%	USP	29/05/2026	Active

Annexure-2: Working Standard Qualification Report

Include results of assay, chromatographic purity, response factor comparison, and analyst’s summary.

Annexure-3: Storage Temperature Monitoring Log

Date	Time	Location	Temperature (°C)	Recorded By
01/06/2025	09:00	Reference Standard Cabinet	5.2	A. Mehra

Annexure-4: Reference Standard Usage Log

Date	Reference ID	Quantity Used (mg)	Analyst	Purpose
01/06/2025	RS/AMD/003/2025	25.0	A. Mehra	Assay Method Validation

Revision History:

Revision Date	Revision No.	Details	Reason	Approved By
01/06/2025	2.0	Added section on qualification and storage documentation	Annual SOP review	Dr. Rakesh Rawat
01/06/2022	1.0	Initial SOP release	New SOP	QA Head