Effective Swabbing Techniques for Cleaning Validation

In the realm of pharmaceutical and biotechnology manufacturing, ensuring equipment and environments are free from contamination is crucial.

This is where cleaning validation comes into play—a process designed to prove that surfaces are clean enough to prevent cross-contamination between production lots. Cleaning validation consists of three primary steps:

1. Cleaning and Rinsing: Ensuring all surfaces are thoroughly cleaned and rinsed.
2. Sampling: Collecting any residual drug or cleaning agent left on the surfaces.
3. Analyzing: Using appropriate instrumentation to analyze the collected samples.

Here, we focus on the second step: sampling surfaces using swabs to ensure any residues are accurately collected for analysis.

Sampling Surfaces with Swabs

TOC Cleaning Validation Swab_sampling swabs

After the cleaning stage, where surfaces are free of visible residue, the challenge is to sample these surfaces reproducibly to capture any invisible residues. The best cleanroom swabs for this purpose are those with heads made of laundered polyester knit fabric, as they offer the lowest levels of releasable particles, highest recovery, and lowest background when Total Organic Carbon (TOC) measurements are used for analysis.

Swabbing Technique:

1. Moistening the Swab:
   • The swab should be damp, not saturated.
   • The moistness level, or percent wetting level, should be consistent, though it need not be identical for each run, as residues can be collected over a range of moistness.
2. Swabbing Pattern:
   • Use a template with a 5 cm x 5 cm opening for consistent sampling of the surface area.
   • Employ linear, overlapping strokes to ensure thorough coverage and collection of residues.

Example Swabbing Pattern Using Two Swabs:

1. First Swab:
   • Swipe the first side horizontally 10 times over the template opening.
   • Flip the swab and swipe the second side vertically 10 times over the same surface.
   • Deposit this swab into a collection vial.
2. Second Swab:
   • Swipe the first side diagonally upwards 10 times.
   • Flip the swab and swipe the second side diagonally downwards 10 times.
   • Deposit this swab into the same collection vial.

This method ensures the surface is swabbed a total of 40 times, maximizing the likelihood of capturing any residues.

Ensuring Accurate Results

Operators can verify their swabbing technique through replicate recovery experiments with known challenges on sample surfaces. While ideally, one would recover 100% of the challenge, recoveries often range from 75% to 80%, influenced by sampling conditions and residue characteristics. Remember, the swab head may not collect all residues, and the extraction liquid may not remove all residues from the swab head. Pre-cleaned vials and swabs are available commercially with TOC background levels of <10 ppb and <50 ppb TOC, respectively, ensuring minimal background interference.

The effective search for “nothing” in cleaning validation involves:

1. Rigorous Cleaning and Rinsing Protocols: Ensuring thorough removal of residues.
2. Proper Swabbing Techniques: Collecting any remaining residues accurately and reproducibly.
3. Use of Pre-cleaned Materials: Minimizing background contamination.

By paying close attention to detail and technique, one can achieve success in proving that equipment and environments are sufficiently clean, ensuring the integrity and safety of pharmaceutical and biotechnology products.