ICH Q6A, WHO TRS, and pharmacopeial standards.

2. Scope

This SOP applies to all primary, secondary, and working reference standards procured, qualified, and used within the AMD department for analytical method development, method validation, and routine analysis.

3. Responsibilities

• Analytical Scientist: Performs testing required for qualification and documents certificate of analysis (CoA).
• QA: Verifies qualification data and authorizes reference standard usage.
• Store Personnel: Ensures proper labeling, storage, and inventory of qualified standards.
• Head – AMD: Approves qualification reports and oversees compliance.

4. Accountability

The Head of Analytical Method Development is accountable for ensuring that only appropriately qualified and approved reference standards are used in all analytical procedures.

5. Procedure

5.1 Classification of Reference Standards

1. Primary Standard: Official standard substance obtained from pharmacopeial sources (e.g., USP, EP, IP).
2. Secondary Standard: In-house standard qualified against a primary standard.
3. Working Standard: Prepared from secondary or primary standard for routine use.

5.2 Procurement and Receipt

1. Obtain primary standards from certified suppliers (e.g., USP, EDQM, NIB).
2. Upon receipt, record details in Annexure-1: Reference Standard Receipt Log.
3. Assign a unique identification code (e.g., RS/2025/001).

5.3 Qualification of Secondary/Working Standards

1. Weigh and prepare standard solution from candidate material.
2. Analyze against certified primary standard using validated method.
3. Perform at least 3 replicates and calculate assay %.
4. Acceptance Criteria: Assay between 98.0–102.0% of label claim with %RSD ≤ 2.0%.
5. Document all results in Annexure-2: Reference Standard Qualification Form.

5.4 Documentation and Approval

1. Prepare Certificate of Analysis (CoA) including:
   • Source and batch no.
   • Physical appearance
   • Water content (if applicable)
   • Assay % and assigned purity
   • Shelf-life
2. Review by QA and approval by Head – AMD.
3. Archive signed CoA in Annexure-3: Reference Standard CoA Register.

5.5 Storage and Labeling

1. Label containers with:
   • Name
   • Code
   • Purity %
   • Date of Qualification
   • Expiry Date
   • Storage Condition
2. Store in desiccator or as per CoA requirements.
3. Maintain Annexure-4: Reference Standard Usage Log.

5.6 Requalification and Expiry

1. Requalification to be done:
   • Every 12 months (if no stability data available)
   • Or as per shelf-life assigned in CoA
2. Destroy expired standards using QA-approved procedure.

6. Abbreviations

• AMD: Analytical Method Development
• RS: Reference Standard
• CoA: Certificate of Analysis
• USP: United States Pharmacopeia
• EP: European Pharmacopoeia
• NIB: National Institute of Biologicals

7. Documents

1. Reference Standard Receipt Log – Annexure-1
2. Reference Standard Qualification Form – Annexure-2
3. Reference Standard CoA Register – Annexure-3
4. Reference Standard Usage Log – Annexure-4

8. References

• ICH Q6A – Specifications: Test Procedures and Acceptance Criteria
• WHO TRS 996 – Annex 3
• USP General Chapter <11> – Reference Standards
• Ph. Eur. Chapter 5.12 – Qualification of Reference Standards

9. SOP Version

Version: 2.0

10. Approval Section

	Prepared By	Checked By	Approved By
Signature
Date
Name
Designation
Department

11. Annexures

Annexure-1: Reference Standard Receipt Log

RS Code	Name	Batch No.	Supplier	Received Date
RS/2025/001	Amlodipine Besylate	AB12345	USP	02/05/2025

Annexure-2: Reference Standard Qualification Form

Sample	Primary Std. Ref	Assay (%)	RSD (%)	Qualified?
RS/2025/002	USP AB12345	99.2	1.2	Yes

Annexure-3: Reference Standard CoA Register

RS Code	Purity	Qualified On	Expiry Date	Approved By
RS/2025/002	99.2%	04/05/2025	04/05/2026	QA Head

Annexure-4: Reference Standard Usage Log

Date	Analyst	Purpose	Quantity Used	Balance
06/05/2025	Sunita Reddy	Assay Development	10 mg	90 mg

Revision History:

Revision Date	Revision No.	Details	Reason	Approved By
04/05/2025	2.0	Added annexures and clarified requalification timelines	Regulatory harmonization