reliability of the analytical procedure.

2. Scope

This SOP applies to the Analytical Method Development (AMD) department and is relevant to all development and validation activities involving finished dosage forms that require placebo interference assessment or matrix effect evaluation.

3. Responsibilities

• Formulation Scientist: Provides placebo composition and supervises its preparation.
• Analytical Scientist: Coordinates placebo analysis and documentation.
• QA: Verifies accuracy of labeling, traceability, and compliance to procedures.
• Head – AMD: Reviews and approves placebo preparation and usage records.

4. Accountability

The Head of AMD is accountable for ensuring that placebos are prepared in accordance with defined formulations, properly characterized, and used appropriately in analytical studies.

5. Procedure

5.1 Placebo Composition and Request

1. Obtain approved placebo formula from the formulation R&D team.
2. Ensure the placebo matches the excipient composition (qualitatively and quantitatively) of the intended product without the active pharmaceutical ingredient (API).
3. Record the request using Annexure-1: Placebo Request Form.

5.2 Preparation

1. Prepare required quantity (typically 10–100 g) of placebo under GMP-like conditions.
2. Use pharmaceutical-grade excipients with proper weighing and blending techniques.
3. Assign a unique Placebo Batch Number (e.g., PLB/2025/001) and document in Annexure-2: Placebo Preparation Log.

5.3 Labeling and Storage

1. Label each container with:
   • Name: “Placebo for [Product Name]”
   • Batch No.: PLB/2025/XXX
   • Date of Preparation
   • Use Before Date (default: 6 months)
   • Storage Condition
2. Store in airtight containers at recommended conditions (typically 25°C/60% RH or desiccator).

5.4 Use in Analytical Method Development

1. Use placebo for:
   • Specificity evaluation (interference at analyte RT)
   • Matrix effect assessment
   • Recovery studies when spiked with API
   • Blank correction in spectrophotometric assays
2. Document analysis in Annexure-3: Placebo Usage Log.

5.5 Qualification and Suitability Check

1. Inject/place placebo sample in method trial to confirm absence of interfering peaks or signal.
2. If interference is observed, modify method (e.g., change wavelength, pH, column, etc.).
3. Attach chromatograms or results in Annexure-4: Placebo Suitability Record.

5.6 Expiry, Retest, and Destruction

1. Default shelf life: 6 months from preparation unless stability data exists.
2. Re-prepare if:
   • Color or physical form changes
   • Contamination or labeling issue is noted
3. Expired or rejected placebo must be discarded as per SOP/QA/042/2025 and logged.

6. Abbreviations

• AMD: Analytical Method Development
• API: Active Pharmaceutical Ingredient
• QA: Quality Assurance
• PLB: Placebo Batch
• RH: Relative Humidity

7. Documents

1. Placebo Request Form – Annexure-1
2. Placebo Preparation Log – Annexure-2
3. Placebo Usage Log – Annexure-3
4. Placebo Suitability Record – Annexure-4

8. References

• ICH Q2(R2) – Validation of Analytical Procedures
• ICH Q14 – Analytical Procedure Development
• WHO Technical Report Series 996 – Annex 3

9. SOP Version

Version: 2.0

10. Approval Section

	Prepared By	Checked By	Approved By
Signature
Date
Name
Designation
Department

11. Annexures

Annexure-1: Placebo Request Form

Requested By	Product Name	Placebo Formula	Quantity	Date
Sunita Reddy	Paracetamol 500 mg	Lactose, MCC, PVP, Talc	50 g	10/05/2025

Annexure-2: Placebo Preparation Log

Batch No.	Prepared By	Excipients	Prepared On	Checked By
PLB/2025/001	Rajesh Kumar	Lactose, PVP, Talc	12/05/2025	QA

Annexure-3: Placebo Usage Log

Date	Analyst	Purpose	Method ID	Remarks
14/05/2025	Ajay Verma	Specificity Check	HPLC/AMD/058	No interference observed

Annexure-4: Placebo Suitability Record

Method	Placebo Batch	Interference	Corrective Action	Status
UV/AMD/102	PLB/2025/001	None	NA	Approved

Revision History:

Revision Date	Revision No.	Details	Reason	Approved By
04/05/2025	2.0	Added Annexure-4 and clarified labeling/storage guidance	Audit findings