The Most Common Analytical Test Methods in Cleaning Validation:
Specific and non-Specific Methods
The success of the cleaning validation shall depend on the correct design and selection of the analytical method and its parameter characteristics to detect contaminants. Some of these testings are physical as visual cleanliness and others are analytical testing.
Exist two (2) types of analytical test methods in cleaning validation: Specific and non-Specific
Surprisingly, you can reach incorrect conclusions of cleanliness based on the inappropriate selection and use of the analytical methods.
The cleaning process’s effectiveness is evidenced by means of testing at the correct design specifications and parameters. e.g. detection limit, quantification limit, etc.
Analytical testing for a specific residual material requires the selection of the most appropriate analytical method applicable for the intended use. In some cases, exist more than one analytical method available to perform the testing and reach similar results.
Specific Test Methods in Cleaning Validation
The most common test methods considered to detect specific ingredients are:
GC-MS (Gas Chromatography-Mass Spectrometry)
A transducer (or sensor) that converts the activity of a specific ion dissolved in a solution into an electrical potential.
Determine the concentration of certain metal ions, among them sodium, potassium, lithium, and calcium.
Uses first or higher derivatives of absorbance with respect to wavelength for qualitative analysis and for
Method for quantitatively assessing protein translocation using proximity-induced enzyme complementation.
Method of quantitative chemical analysis to determine the concentration of an identified analyte (a substance to be analyzed).
Non-Specific Test Methods in Cleaning Validation
The most common methods utilized to detect the presence of a blend of ingredients are:
The amount of carbon found in an organic compound and is often used as a non-specific indicator of water quality or cleanliness of pharmaceutical manufacturing equipment.
The scale used to specify the acidity or basicity of an aqueous solution
Measuring the ionic content in a solution is linked directly to the total dissolved solids (T.D.S.)
The preferred test methods in cleaning validation
The FDA prefers specific methods but will accept non-specific methods with adequate rationales for their use. For investigations of failures or action levels, a specific method is usually preferable.
Considerations to select the correct test methods in cleaning validation
It involves the evaluation and determination of the specificity and sensitivity of the analytical method used to detect residuals or contaminants.
With advances in analytical technology, residues from the manufacturing and cleaning processes can be detected at very low levels.
If levels of contamination or residual are not detected, it does not mean that there is no residual contaminant present after cleaning. It only means that levels of contaminants greater than the sensitivity or detection limit of the analytical method are not present in the sample.
The firm should challenge the analytical method in combination with the sampling method(s) used to show that contaminants can be recovered from the equipment surface and at what level, i.e. 50% recovery, 90%, etc. This is necessary before any conclusions can be made based on the sample results.
A negative test may also be the result of poor sampling technique (see below).
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CONSIDERATIONS TO SELECT THE CORRECT TEST METHOD
TOP CLEANING VALIDATION FACTORS AND LEVELS
ESTABLISHMENT OF ACCEPTABLE CRITERIA
STATUTORY AND REGULATORY REQUIREMENTS
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References: Test Methods in Cleaning Validation
PIC/S Guideline to Validation – PI -006-3 (2007)
ICH Guideline Q7 “GMP for APIs
Inspection Guide for Bulk Pharmaceutical Chemicals and the Biotechnology Inspection Guide