applies to all certified reference standards used in the development, qualification, and validation of analytical methods for APIs and drug products. It includes reference materials procured from pharmacopoeias (e.g., USP, EP), commercial vendors, or in-house developed working standards.

3. Responsibilities

• Analytical Chemist: Responsible for receipt, verification, and proper handling of CRSs.
• Store Coordinator: Maintains inventory and storage records of CRSs.
• Quality Assurance: Reviews CRS qualification documents and approves in-house reference standards.
• AMD Manager: Ensures compliance with SOP and regulatory expectations.

4. Accountability

The Head of Analytical Method Development is accountable for ensuring the availability, qualification, traceability, and appropriate usage of CRSs in method development and validation.

5. Procedure

5.1 Procurement of Certified Reference Standards

1. Procure CRS from official sources (e.g., USP, EP, BP) or qualified vendors with traceability documentation and CoA (Certificate of Analysis).
2. Document vendor approval and purchase justification (Annexure-1).

5.2 Receipt and Verification

1. Inspect CRS packaging upon receipt for integrity, labeling, and compliance with purchase order.
2. Verify the following:
   • Product name and catalog number
   • Batch number and expiration date
   • Storage conditions
   • CoA traceability and lot-specific data
3. Record the CRS in the inventory register (Annexure-2).

5.3 Storage Conditions

• Store CRSs as per manufacturer’s recommendations (e.g., 2–8°C for light-sensitive compounds).
• Use desiccators, refrigeration units, or light-protective containers as required.
• Ensure temperature and humidity monitoring logs are maintained daily.

5.4 Qualification of In-House Reference Standards

1. When CRS is not available, prepare a primary working standard (PWS) using a validated lot of API.
2. Compare analytical results of PWS with available pharmacopeial or certified standards.
3. Evaluate purity by chromatographic methods, moisture by Karl Fischer, and calculate correction factors.
4. Prepare a qualification report and submit to QA for approval (Annexure-3).

5.5 Usage and Documentation

1. Label all standard containers with:
   • Substance name and batch number
   • Date of opening and expiry
   • Storage condition and user initials
2. Record usage in the CRS usage logbook (Annexure-4).
3. Do not reuse containers once expired or contaminated.

5.6 Retesting and Re-qualification

• For CRSs without expiry date, perform retesting at defined intervals (e.g., annually) based on stability data.
• Document retest results and extend validity upon QA approval only.

5.7 Disposal

• Expired or rejected standards must be labeled ‘To Be Discarded’ and moved to the designated rejection area.
• Dispose of according to SOP on hazardous chemical disposal (refer to SOP/QA/054/2025).

6. Abbreviations

• CRS: Certified Reference Standard
• CoA: Certificate of Analysis
• PWS: Primary Working Standard
• QA: Quality Assurance
• SOP: Standard Operating Procedure

7. Documents

1. Annexure-1: CRS Purchase and Verification Form
2. Annexure-2: CRS Inventory Register
3. Annexure-3: In-House Qualification Report Format
4. Annexure-4: CRS Usage Logbook

8. References

• ICH Q6A – Specifications: Test Procedures and Acceptance Criteria
• Pharmacopoeial standards (USP, EP, BP)
• 21 CFR Part 211.84 – Testing and Approval or Rejection of Components

9. SOP Version

Version: 2.0

10. Approval Section

	Prepared By	Checked By	Approved By
Signature
Date
Name	Vaibhav Singh	Reema Pillai	Dr. Harshita Goyal
Designation	Analytical Chemist	QA Reviewer	Head – AMD
Department	Analytical Method Development	Quality Assurance	Analytical Method Development

11. Annexures

Annexure-1: CRS Purchase and Verification Form

Product Name	Catalog No.	Vendor	Batch No.	Expiry	Checked By
Caffeine CRS	USP-1101	USP	CRS-1098	2026-09	Reema Pillai

Annexure-2: CRS Inventory Register

Sr. No.	Name	Batch No.	Opened On	Expiry	Status
1	Paracetamol CRS	PCRS-1001	01/05/2025	31/05/2026	Active

Annexure-3: In-House Qualification Report Format

Report No.: AMD/IHQS/385/2025
Substance: Metformin Working Standard
Purity: 99.78% (by HPLC)
Moisture Content: 0.5%
Correction Factor: 0.994
Approved By: QA Manager

Annexure-4: CRS Usage Logbook

Date	User	Standard	Batch No.	Purpose	Remarks
01/06/2025	V. Singh	Aspirin CRS	ASP-789	Assay Calibration	Standard weighed and diluted

Revision History

Revision Date	Revision No.	Details	Reason	Approved By
01/06/2025	2.0	Expanded qualification and storage guidelines	Annual review	Dr. Harshita Goyal
02/05/2022	1.0	Initial version	New SOP	QA Head