Frequency of Cleaning
Pharma processing equipment is cleaned in one of two ways: clean-in-place methods (performed without disassembling) and clean-out-of-place methods (parts are removed and washed separately in an equipment wash area). Depending upon past and intended usage of equipment, the types of cleaning are:
Type A (minor): This type of cleaning takes place between two batches of the same product, or when there is changeover of manufacture of the drug from lower strength to higher strength. This is also done when the strength remains the same, but the colour/flavour change.
It consists partly of clean-in-place, and partly cleanout- of-place methods.
Type B (major): This type of cleaning is done between the manufacture of different kinds of products on the same equipment or when there is changeover of manufacture of the drug from higher strength to lower strength. It is also carried out at the end of each working day.
This comprises only clean-in-place methods.
Type C: For the processing rooms which are not used during the day.
Cleaning Validation
Cleaning procedure must effectively remove residues of a product and a cleaning agent from the manufacturing equipment, to a level that does not raise patient safety concerns. Validation of cleaning methods provides documented evidence that an approved cleaning procedure will provide clean equipment, suitable for its intended use.
Cleaning validation is done by one of two common methods:
• Rinse samples: Analytical determination of a sample of the last rinsing solvent used in the cleaning procedure. The volume of solvent used for the last rinse must be known.
• Swab sampling: Based on the physical removal of residue left over on a piece of equipment after it has been cleaned and dried. A swab wetted with a solvent is rubbed over a previously determined sample surface area to remove any potential residue, and extracted into a known volume of solvent in which the contaminant active ingredient residue is soluble.
Parameters
By measuring the levels of certain impurities left on the equipment after cleaning, using either of the above methods, one can determine the efficacy of cleaning:
• Total Solids: Quantities of non-volatile liquid in liquid extracts, either in rinses or swabs results of the surface. Used for both organic and in-organic materials.
• pH test: for determining the presence of alkaline or acid cleaning materials in the final rinse.
• Specific Ion Meters: for quantifying low levels of specific ions generally from ionic materials. Useful for confirming the level of residual acidic or basic detergents in the final rinse, as determined by the pH test.
US-FDA Standards
The US Drug authority has mandated certain standards for acceptable levels of impurities – either from cleaning chemicals or previously manufactured drugs – in a fully processed unit sold to consumers:
• Not more than 0.1% of the normal therapeutic dose (amount used in a single dose for treatment) of any product should appear in the maximum daily dose of the product that is manufactured on the same equipment, after it.
• Not more than 10ppm of any product to appear in another product.
• No quantity of residue to be visible on the equipment after cleaning procedures are performed.
