Cleaning validation

Cleaning validation/verification is a critical step in manufacturing process control, requiring fast analysis of a large number of samples to check for the presence of leftover API or cleaning agents.

Despite the high premium on speed, the current standard technique, HPLC, requires a substantial amount of time per sample. TOC, while faster, is non-specific and limited to aqueous samples. Ion Mobility, on the other hand, offers compound-specific detection in the ppb-ppm range combined with analysis times in seconds, not minutes, making it a prime candidate for efficient cleaning validation.

The core advantages of IMS for Cleaning Validation are:

  • Speed - answers in seconds, not minutes

  • Size - small enough for use at line

  • Specificity - pinpoint the API or detergent

  • Simplicity - no columns, no vacuum, or large amounts of solvent

  • Ease of method development - ideal for large numbers of APIs

 Click the video below for an introduction to IMS for Cleaning validation:

The GA2200 CV for Cleaning Validation

 With the recent upgrade to full 21 CFR part 11 regulatory compliance, the Excellims GA2200 CV offers an impressive array of feature that make it an ideal solution for cleaning validation:

  • A versatile ESI source, able to ionize non-volatile and thermally sensitive compounds in a variety of different solvents (swab extract and rinse samples)

  • IMS speed advantage with 30 s measurement time for ppb-ppm level samples with an RSD of 5-10%

  • A high resolving atmospheric drift tube (R > 70), allowing for specific identification and quantification of APIs and detergents

  • All features required for full 21 CFR part 11 compliance, e.g. restricted individual user access, different user levels, sample and method protection, electronic signatures and a comprehensive electronic audit trail

While earlier offerings of IMS for cleaning validation used thermal desorption to volatilize and ionize the samples, the GA was developed with an electrospray (ESI) ion source, providing soft ionization of non-volatile molecules, including antibiotics and large biomolecules (click to enlarge):

Spectra on the GA2200 CV show detection limits in the ppb-ppm (compound dependent), a linear range of 2-3 orders of magnitude and excellent repeatability, as demonstrated here for an antibiotic (click to enlarge):

Typical repeatability is 5-10% (RSD) and sample recovery is comparable to HPLC as shown here for multiple swabs samples prepared with known amounts of an analgesic (click to enlarge):

With its compact design, large touchscreen and the recent upgrade to the 21 CFR part 11 compliant software package, the GA2200 now offers a full solution for at-line cleaning validation. Instrument parameters and calibration curves are saved as methods which can be recalled by the analyst (to edit, laboratory manager credentials are required). The instrument offers operator and method development modes, electronic signatures and a comprehensive audit trail.

To learn more, please check out the materials below or contact our applications & sales specialists. We will be happy to organize an instrument demonstration using your samples.