SOP applies to all reference standards procured from recognized pharmacopeial sources or certified manufacturers and working standards prepared internally at the AMD laboratory of API and formulation facilities.

3. Responsibilities

• Analytical Chemist: Responsible for preparation, qualification, and maintenance of WS from RS.
• QA Department: Verifies qualification protocol, reviews documentation, and approves WS usage.
• AMD Head: Authorizes RS and WS qualification reports and ensures regulatory compliance.

4. Accountability

The Head of Analytical Method Development is accountable for the scientific integrity, regulatory compliance, and traceability of reference and working standards in the laboratory.

5. Procedure

5.1 Procurement and Receipt of RS

1. Procure RS from official sources (USP, BP, EP, Ph. Eur., IP, WHO, NIB).
2. On receipt, check packaging integrity, certificate of analysis (CoA), and batch number.
3. Label as “Reference Standard – For Laboratory Use Only” with date of receipt and expiry.

5.2 Storage of RS

1. Store as per label conditions (e.g., 2–8°C, protect from light, desiccator, etc.).
2. Ensure temperature and humidity-controlled environment for stability.
3. Maintain RS Stock Register (Annexure-1) with quantity, batch number, and expiry.

5.3 Preparation of WS from RS

1. Weigh appropriate amount of RS with analytical balance having 4-decimal precision.
2. Dilute with suitable solvent to prepare stock solution at required concentration.
3. Divide into amber glass vials and label with WS code, potency, preparation date, and retest date.
4. Store WS in refrigerated condition or as required based on stability data.

5.4 Qualification of WS

1. Compare WS performance against RS in at least three analytical parameters (e.g., assay, purity, retention time, area response).
2. Ensure results are within acceptable variation limit (typically ±2%).
3. Record qualification results in WS Qualification Template (Annexure-2).
4. QA to review and approve before first-time usage in routine analysis or method validation.

5.5 Retest and Requalification

1. Assign retest period of 6 or 12 months based on WS stability or ICH Q1 guidelines.
2. Prior to expiry or retest date, perform comparative analysis again with fresh RS.
3. Destroy WS immediately if it fails requalification or physical inspection criteria.

5.6 Documentation and Traceability

1. Maintain RS CoAs, WS preparation records, usage logs, and calibration curves in secure binders or validated LIMS.
2. Generate internal identification numbers for all RS/WS for traceability across reports.
3. Ensure logbook entries are reviewed and countersigned.

6. Abbreviations

• RS: Reference Standard
• WS: Working Standard
• CoA: Certificate of Analysis
• QA: Quality Assurance
• LIMS: Laboratory Information Management System

7. Documents

1. Annexure-1: Reference Standard Stock Register
2. Annexure-2: Working Standard Qualification Template
3. Annexure-3: WS Usage Log

8. References

• ICH Q6A: Specifications: Test Procedures and Acceptance Criteria
• USP <11> – Reference Standards
• Ph. Eur. Chapter 5.12 – Reference Standards
• 21 CFR Part 211.194 – Laboratory Records

9. SOP Version

Version: 2.0

10. Approval Section

	Prepared By	Checked By	Approved By
Signature
Date
Name	Ravi Tiwari	Neha Sharma	Dr. R. K. Sinha
Designation	Analyst – AMD	QA Executive	Head – AMD
Department	Analytical Method Development	Quality Assurance	Analytical Method Development

11. Annexures

Annexure-1: Reference Standard Stock Register

RS Code	Material Name	Source	Batch No.	Expiry	Quantity	Storage
RS-001	Paracetamol	USP	22APC001	Dec-2026	1 g	2–8°C

Annexure-2: Working Standard Qualification Template

Include: RS vs WS comparison, chromatogram overlays, peak area values, assay comparison, conclusion, and QA comments.

Annexure-3: WS Usage Log

Date	WS Code	Analyst	Purpose	Qty Used	Balance	Signature
01/06/2025	WS-PCT-001	A. Kumar	Method Validation	50 mg	950 mg

Revision History:

Revision Date	Revision No.	Details	Reason	Approved By
01/06/2025	2.0	Added requalification procedure and usage log format	Annual Review	Dr. R. K. Sinha
01/05/2022	1.0	Initial Release	New SOP	QA Head