extractables and leachables and do not interfere with analysis.

Step 2: Define Sampling Locations (Worst Case)

Using a risk-based approach, identify worst-case sampling points based on:

• Surface roughness
• Material type (e.g., stainless steel, glass)
• Cleanability
• Product contact area
• Historical difficulty to clean

Example: Gasket interfaces, agitator shafts, dead legs, spray balls, transfer ports.

Step 3: Perform Recovery Factor Study

Recovery studies determine the efficiency of the swabbing process. They simulate real-world cleaning conditions and assess how much residue can be extracted from a known surface.

Procedure:

1. Spike a known amount of analyte on a test coupon (e.g., 316L SS, 10 cm x 10 cm)
2. Allow to dry under ambient conditions
3. Swab using the same technique intended for routine use
4. Extract analyte from swab using validated solvent
5. Analyze and calculate recovery %

Spiked Amount (µg)	Recovered (µg)	% Recovery
100.0	88.0	88%
100.0	91.5	91.5%
100.0	89.2	89.2%

Acceptance Criteria: ≥ 85% recovery is typically considered acceptable unless justified otherwise.

Step 4: Analytical Method Validation

The method used to quantify residues must be validated per ICH Q2 guidelines for:

• LOD: Minimum level detected (e.g., 0.002 µg/cm²)
• LOQ: Minimum quantifiable level (e.g., 0.005 µg/cm²)
• Specificity: No interference from swab, solvent, or matrix
• Linearity: Typically r² ≥ 0.999
• Accuracy & Precision

Chromatographic methods (HPLC, UV, TOC) are often used based on residue type. TOC is non-specific and used primarily for cleaning agent residues.

Step 5: Set Acceptance Limits – PDE, MACO & Visual Cleanliness

Determine Maximum Allowable Carryover (MACO) based on PDE or therapeutic dose of previous product:

MACO Formula (PDE-Based):

MACO (mg/swab area) = (PDE x Min Daily Dose of next product) / (Surface Area x Safety Factor)
      

Example for swabbed surface area of 100 cm²:

• PDE: 3 mg/day
• Min Dose of next product: 200 mg
• Surface Area: 1.5 m²
• MACO: ~0.002 mg/100 cm² = 20 µg/swab

Limits must also meet visual cleanliness criteria — “no visible residue” under defined lighting and inspection angles.

Step 6: Execute the Swab Sampling

Follow a validated SOP. Key practices:

• Use sterile gloves, label all swabs, avoid contamination
• Swab defined surface area using vertical and horizontal strokes
• Rotate swab head and use firm pressure
• Place swab into extraction tube with solvent immediately
• Document surface ID, operator, date/time, lot info

Step 7: Evaluate Results and Take Actions

Compare analytical results with calculated acceptance limits. Investigate any OOS or borderline results. Confirm cleanability and adjust cleaning SOPs if necessary.

Documentation and Reporting

• Swab Sampling Protocol
• Recovery Factor Report
• Analytical Method Validation Report
• Swab Results Summary Table
• Final Cleaning Validation Report

Regulatory References

• FDA Process Validation Guidance
• EMA Annex 15 – Cleaning Validation
• ICH Q2, Q7
• WHO TRS 1019 Annex 3

Conclusion

Swab sampling remains the gold standard for residue detection in cleaning validation. A sound recovery study, validated analytical method, and risk-based sampling approach ensure that cleaning processes are effective and defensible during inspections. Pharmaceutical companies must align their strategies with regulatory guidance, scientific evidence, and GMP expectations to maintain a state of control and product safety.

Explore swab SOP templates and recovery data archives at PharmaSOP.in and validation case studies at ClinicalStudies.in.