HPIMS cleaning validation technology

Cleaning Validation Technology

Cleaning validation/verification is an FDA requirement at the conclusion of a pharmaceutical manufacturing run. Inadequate or incomplete cleaning validation analysis is one of the leading causes of internal investigations and regulatory citings. Current technologies keep production equipment off line as they are either too slow, not specific, inconvenient, or not sensitive enough. The need to perform fast analysis of a large number of samples to check for the presence of leftover API or cleaning agents, is a need of the global pharmaceutical manufacturing industry.

FDA guidance cleaning validation

The FDA has required equipment cleaning since 1978 (cGMP guidelines for cleaning validation) to prevent contamination or adulteration of drug products. The guidelines do not specify which cleaning validation technology to use, it puts the onus on operations teams to ‘determine the specificity and sensitivity of the analytical method used to detect residuals or contaminants’. Users must ensure they deploy analytical technology that can detect residues from the manufacturing and cleaning processes at very low levels.

These performance requirements are often to the detriment of speed of analyses.

Cleaning Validation Technology

There are several different analytical approaches for cleaning validation. While some traditional lab-based techniques like HPLC have high precision and accuracy, they are relatively slow and require the sample to be transferred to an external quality lab and the production euipment sits idle until the results confirm cleanliness. Other techniques, such as TOC swab analysis, are more mobile, faster, and can even be handheld to deliver a result on the production floor, but sacrifice performance with speed.

High performance ion mobility spectrometry increases production efficiency by cutting operating costs and reducing downtime.

With Excellims’ standalone High performance ion mobility instrument, the GA2200, you can:

Get production equipment back online faster between different manufacturing batches/lines:
Identify, directly on the production line, if there are trace residues left from previous manufacturing that could cross-contaminate the final product.
Achieve significant cost savings
Cleaning validation can be done in minutes, rather than days (as is currently the case with HPLC or TOC). The quicker the production line is redeployed between batches; the more product is manufactured (and sold)
GMP 21 CFR Part 11 compliant
No compromise between performance and speed

TOC Swab Cleaning Validation

TOC analysis is commonly used for testing cleaning validation samples. TOC cleaning validation involves the oxidation of carbon and the detection of the resulting carbon dioxide produced from the oxidation reaction. Sensitivity is down to the ppm or ppb level. TOC is a non-specific method of analysis. All organic carbon is detected. Residues for TOC analysis must dissolve in water. This requirement could limit the effective linear range of the residue assay.

Cons:

Not specific (Total Carbon Only)
Limited vendors who can supply GMP-compliant technology
Compromise performance for speed

Watch this video to learn more about the GA2200 for cleaning validation

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HPLC Cleaning Validation

HPLC for cleaning validation is also well established. HPLC is a chromatographic method that separates the residue of interest from the components of the formulation as well as the detergent. Typically, HPLC methods for cleaning validation are designed to quantitate levels down to 0.1% of the API, making sensitivity well below required acceptance limits. However, the sensitivity of HPLC is dependent on the chemical structure of the residue of interest and the detector, which can quantitate the residue. A residue with no UV chromophore requires either a specialized detector (fluorescence, electrochemical) or derivatization to achieve the desired sensitivity. HPLC assay methods can be lengthy (i.e., 30-40 minutes per injection), which could be an issue for quick turnaround of samples.

Cons:

Relatively slow (12-20 minutes)
Need to send samples off to a lab to be analyzed
Costly operation and maintenance
Skilled user required

Cleaning Validation Technology

FDA guidance cleaning validation

Cleaning Validation Technology

Cleaning Validation Can be More Efficient

High performance ion mobility spectrometry increases production efficiency by cutting operating costs and reducing downtime.

With Excellims’ standalone High performance ion mobility instrument, the GA2200, you can:

TOC Swab Cleaning Validation

Watch this video to learn more about the GA2200 for cleaning validation

HPLC Cleaning Validation

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