ensures traceability, integrity, and compliance with regulatory requirements.

2. Scope

This SOP applies to all qualified personnel handling primary, secondary, and working reference standards within the Analytical Method Development (AMD) department at pharmaceutical API or formulation facilities.

3. Responsibilities

• Analyst: Responsible for checking integrity and labeling before use, performing qualification tests, and ensuring accurate usage records.
• AMD Documentation Officer: Maintains reference standard inventory log and qualification records.
• QA Reviewer: Verifies qualification certificates, audit trails, and reviews related documentation for compliance.

4. Accountability

The Head of Analytical Method Development is accountable for overall control, periodic review, and ensuring that all procedures related to reference standards are properly followed and documented.

5. Procedure

5.1 Types of Reference Standards

• Primary Standards: Certified by official pharmacopoeia or national authority (e.g., USP, EP, IP).
• Secondary Standards: In-house qualified materials, standardized against a primary standard.
• Working Standards: Daily-use materials prepared from primary or secondary standards.

5.2 Receipt and Inspection

1. Upon receipt, verify the following:
   • Certificate of Analysis (CoA)
   • Manufacturer’s details and batch number
   • Date of manufacture and expiry
   • Physical integrity and packaging condition
2. Enter details in Reference Standard Receipt Log (Annexure-1).

5.3 Qualification of Working Standards

1. Use primary or secondary standard to establish potency of working standard.
2. Perform at least three replicate assays against the reference material.
3. Calculate average purity, assign expiry date, and document in Qualification Report (Annexure-2).

5.4 Labeling and Identification

1. Each vial or container should carry:
   • Name of the substance
   • Batch No.
   • Assigned purity
   • Date of preparation
   • Assigned expiry and requalification date

5.5 Storage Conditions

1. Store as per the CoA or label instructions (e.g., 2–8°C or ambient).
2. Maintain dedicated storage cabinets with access control.
3. Monitor temperature daily using calibrated thermometers.

5.6 Usage and Documentation

1. Before use, visually inspect standard for any signs of degradation or contamination.
2. Weigh required quantity using calibrated balances.
3. Record usage in Reference Standard Usage Log (Annexure-3).
4. Do not return unused portions to the original container.

5.7 Requalification and Expiry Management

1. Requalify standards every 6–12 months or as per internal SOP.
2. Destroy expired standards following the destruction log procedure.
3. Update inventory and logs upon requalification or disposal.

6. Abbreviations

• CoA: Certificate of Analysis
• USP: United States Pharmacopeia
• EP: European Pharmacopoeia
• IP: Indian Pharmacopoeia
• QA: Quality Assurance

7. Documents

1. Annexure-1: Reference Standard Receipt Log
2. Annexure-2: Qualification Report Template
3. Annexure-3: Usage Log Format

8. References

• ICH Q7 – GMP for Active Pharmaceutical Ingredients
• WHO Technical Report Series No. 992
• USP <11> – Reference Standards

9. SOP Version

Version: 2.0

10. Approval Section

	Prepared By	Checked By	Approved By
Signature
Date
Name	Priyanka Das	Sumit Sinha	Dr. Nivedita Menon
Designation	AMD Analyst	QA Reviewer	Head – Analytical Method Development
Department	Analytical Method Development	Quality Assurance	Analytical Method Development

11. Annexures

Annexure-1: Reference Standard Receipt Log

Date	Standard Name	Batch No.	Purity (%)	Expiry	Storage Condition
01/06/2025	API-A	RSB202501	99.8	31/05/2026	2–8°C

Annexure-2: Qualification Report Template

Include: source material details, assay results, average purity, calculation of correction factor, expiration date assignment, analyst and reviewer signature.

Annexure-3: Reference Standard Usage Log

Date	Standard Name	Batch No.	Qty Used (mg)	Purpose	Used By
02/06/2025	API-A	RSB202501	50	Assay Validation	Ritika Joshi

Revision History:

Revision Date	Revision No.	Details	Reason	Approved By
01/06/2025	2.0	Updated requalification timelines and clarified storage guidelines	Periodic Review	Dr. Nivedita Menon
15/05/2022	1.0	Initial issue	New SOP	QA Head