Cleanliness monitoring
We routinely measure plant cleanliness on batch changeover, but we occasionally find cross-contamination between batches.
Is cleanliness something that could be monitored by surface analysis?
Chris Pickles
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Many industries, from aerospace to medical devices, conduct cleaning procedures. In general, these industries are concerned
with the cleanliness of the component and test methods are based on rinsing residues. These procedures provide no information
on the residues remaining on the part that, in the case of a prosthesis, could be a critical factor. In the pharmaceutical
industry, the consequences of inadequate clean down can result in cross-contamination and cause significant product loss either
through quality control reject levels or, more seriously, product recalls. A cleanliness monitoring procedure based on measurements
of the material remaining on surfaces after they have been subject to the cleaning process can minimize the potential for
cross-contamination.
An analytical protocol for the measurement of surface chemistry, such as CERAM Surface and Materials Analysis's Validata,
can be applied throughout a manufacturing activity and can include raw material confirmation, process validation, quality
acceptance and packaging specification. Measurements can be made on components directly, on swabs or leachates, or on coupon
'blanks' sent through the process. The procedure analyses the surface of interest for all potential contaminants once the
composition of an acceptably clean surface for the application concerned has been established — the specified cleanliness
level threshold. The analytical method used is highly sensitive to all elements and the data reduction protocol uses a proprietary
combinatorial algorithm to generate a single figure 'cleanliness index' ranging from 0 to 100%. In practice, figures lie between
40–99.5% depending on material, process and potential contaminants. The benefit of an analytical procedure for manufacturers is that they receive a complete cleanliness validation service based
on assessment of the specific application with a 'Go/No Go' decision in the form of a single figure that is directly related
to the specification requirement.
In a recent case of inadequate clean down between production cycles, a potential contamination was detected on paracetamol
tablets. Surface analysis of a suspect tablet revealed traces of Chloroquin (an antimalarial). There were also traces of production
plant lubricating oil, which caused tablet discolouration.1
Tablets from another batch produced at the same plant were not discoloured, but still contained traces of Chloroquin on their
surface. Control tablets manufactured at another plant gave a 'clean' paracetamol spectrum.
In this case study, the company made significant cash savings and created a permanent solution to a manufacturing issue connected
with plant clean down between production cycles.
The moral of the story is that all of this could have been prevented if a surface analysis protocol had been implemented during
the development and validation of specifications for the original plant clean-down procedures.
Controlled release
We are developing a product where the API is coated with a polymer layer. Is it possible to determine the thickness of the
layer using surface analysis?
Many drug formulations are delivered through controlled release mechanisms, one of which is the encapsulation of the API with
other formulation components as a bead within a slowly soluble, multilayer polymer coating. As the solubility of the encapsulate
determines the rate of drug release, it is critical that the coating is both correctly formulated and applied. The validation
of process capability to ensure that a coherent coating is being produced consistently can be achieved by surface analysis
of coated bead cross-sections.
Surface mass spectrometry can identify organic species of high molecular weight from which spatial chemical maps can be generated.
These spatial chemical maps of different species have exceptional parts per million sensitivity and micron resolution. Surface
mass spectrometry is, therefore, ideally suited to providing information on coating thickness and integrity/uniformity. Moreover,
it can provide speciated chemical images of the location and distribution of the formulation ingredients within the drug-containing
bead.
