rinse sampling results used to confirm cleanliness of pharmaceutical manufacturing equipment.

2. Scope

This SOP applies to the Analytical Method Development (AMD) department for all cleaning validation and verification studies involving swab or rinse sampling methods to detect residual APIs, excipients, or cleaning agents.

3. Responsibilities

• Analytical Scientist: Conducts surface spiking, sample recovery, and recovery factor calculation.
• QC Analyst: Performs parallel swab or rinse testing and supports method reproducibility studies.
• QA Executive: Reviews and approves recovery validation reports for inclusion in cleaning validation protocols.

4. Accountability

The Head of Analytical Method Development is accountable for ensuring the scientific integrity and regulatory compliance of recovery factor determination for cleaning validation purposes.

5. Procedure

5.1 Surface Preparation

1. Use stainless steel (SS-316), glass, or product-contact surface coupons representative of equipment.
2. Clean surfaces thoroughly and dry before spiking.

5.2 Analyte Spiking

1. Prepare analyte solution (e.g., 100 µg/mL) in appropriate diluent (e.g., water, mobile phase).
2. Apply a known volume (e.g., 100 µL) onto a defined area (25 cm²) of the test surface using micropipette.
3. Allow to air dry under laminar airflow until completely dry.

5.3 Recovery Procedure

1. For swab sampling:
   • Swab the spiked surface using validated swab technique (horizontal, vertical, diagonal).
   • Extract the swab in 10 mL of diluent with sonication or vortex mixing.
2. For rinse sampling:
   • Rinse the spiked surface with a known volume of diluent (e.g., 25 mL) and collect entire volume.

5.4 Analytical Testing

1. Analyze the recovered solution using validated analytical methods (e.g., HPLC, TOC).
2. Calculate recovery percentage using:
   
   Recovery (%) = (Recovered Amount / Spiked Amount) × 100

5.5 Acceptance Criteria

1. Acceptable recovery:
   • ≥80% for APIs and cleaning agents
   • ≥50% for microbiological or TOC-based methods (unless otherwise justified)
2. Repeat study in triplicate to confirm reproducibility with %RSD ≤ 15%.

5.6 Documentation

1. Document spiking details, surface type, sample preparation, analysis results, and recovery calculation in Annexures.
2. Prepare and approve a recovery factor validation report.

6. Abbreviations

• API: Active Pharmaceutical Ingredient
• TOC: Total Organic Carbon
• HPLC: High Performance Liquid Chromatography
• RSD: Relative Standard Deviation
• QA: Quality Assurance

7. Documents

1. Recovery Factor Worksheet – Annexure-1
2. Surface Coupon Identification Log – Annexure-2
3. Recovery Validation Summary Report – Annexure-3

8. References

• ICH Q2(R1): Validation of Analytical Procedures
• FDA Guidance for Industry: Cleaning Validation
• WHO TRS 1025: Annex 3 – Cleaning Validation Guidelines

9. SOP Version

Version: 2.0

10. Approval Section

	Prepared By	Checked By	Approved By
Signature
Date
Name	Amita Kulkarni	Ravi Nair	Sunita Reddy
Designation	Analytical Scientist	QA Reviewer	Head – AMD
Department	Analytical Method Development	QA	Analytical Method Development

11. Annexures

Annexure-1: Recovery Factor Worksheet

Surface Type	Spiked Amount (µg)	Recovered Amount (µg)	Recovery (%)	Status
SS-316	100	88	88%	Pass

Annexure-2: Surface Coupon Identification Log

Coupon ID	Material	Dimensions (cm)	Cleaning Status	Verified By
CPN-001	SS-316	5 × 5	Clean	QA Officer

Annexure-3: Recovery Validation Summary Report

Recovery factor for Metformin determined to be 88% on SS-316 surface using swab technique. Method validated with three replicates showing RSD 4.2%. Method deemed acceptable for cleaning validation studies.

Revision History:

Revision Date	Revision No.	Details	Reason	Approved By
21/05/2025	2.0	Updated with rinse method recovery protocol and clarified acceptance ranges	Annual Review	Sunita Reddy
06/04/2022	1.0	Initial SOP Release	New SOP	QA Head