What is Cleaning Validation?
Cleaning validation is used to ensure that a cleaning procedure removes all trace soils, cutting fluids, fingerprints, particulates and cleaning agents from surfaces in regulated processes. Any residue must be removed to a predetermined level of cleanliness. Cleaning validation processes protect against the cross-contamination of ingredients from one batch to another, ensure that surfaces or devices are free of residue prior to any further sterilization process, and assist in ensuring product quality.
Cleaning validation is required for use in industries following Good Manufacturing Practices (GMP) as outlined by the US FDA. Manufacturers in the pharmaceutical, medical device and food and beverage industries all use cleaning validation methods to ensure that their equipment is free of waste and that subsequent products manufactured on that equipment are not jeopardized by any remaining soils or soap residue.
FDA guidelines for cleaning validation require specific written procedures detailing how cleaning processes will be validated. These should include:
- Who is responsible for performing and approving the validation
- Acceptance criteria
- When revalidation is required
- Sampling procedures
- Analytical methods to be used
- Documentation of the studies and results
- A final conclusive report stating that all residues have been removed to the predetermined level
If any part of the cleaning process is changed, the cleaning validation process must also be updated.
Cleaning Validation Methods
Various analytical methods can be used to detect cleaner residues on equipment. Each method is unique to the specific cleaner used. Cleaner manufacturers should be able to provide detailed validation methods for their products.
Regulated industries rely, in most cases, on quantitative validation methods. Quantitative validation methods provide measurable and exact results, whereas qualitative validation methods involve more subjective methods, such as visual observations.
HPLC (High Performance Liquid Chromatography)
HPLC stands for high performance liquid chromatography. HPLC validation methods can pinpoint exact ingredients. This validation method uses pressure to force a solution through columns to separate, identify and quantify each of its components.
The columns are filled with a solid adsorbent substance. As the solution is forced through the column, each of its components reacts differently to this substance. This results in varying flow rates for each component in the solution. The sample solution is separated into its individual elements by the rate at which they flow out of the column.
Once the individual components of the sample solution are separated, various types of detectors can be used for identification. Some common detectors include:
CAD – charged aerosol detector
DAD – diode array detector
MS – mass spectrometry
HPLC validation methods separate liquids into their individual components. This information is then used to determine the level of residue of an individual component so that predetermined acceptable levels of cleanliness are met. HPLC is the most common type of quantitative cleaning validation method currently used.
TOC (Total Organic Carbon)
TOC stands for total organic compound. TOC validation methods detect carbon content in a tested sample. The results are not ingredient specific. The amount of carbon in the sample can come from any one of a number of varying sources including contamination, a dirty tank, testing equipment, ingredient residue or cleaner residue. The objective is that the overall results of TOC testing meet the predetermined acceptable levels. Results that exceed the predetermined levels are not acceptable.
UV VIS stands for ultraviolet visible spectroscopy. This detection method relies upon the absorption of light to quantitate chemicals at specific wavelengths. Sometimes, a chemical agent is added to the rinse water sample to make key ingredients visible. Chemicals absorb light differently at different wavelengths.
Methylene blue, for example, is routinely used to react to sulfonate surfactants and detect detergent residue. The intensity of the color is an indication of how much sulfonate remains in the sample.
In the illustration above, the fluid at the top of the tubes shows the water in the solution. The fluid on the bottom indicates the amount of chloroform in the test sample. As the concentration of Micro-90 increases, more sulfonate is being pulled out of the top water level by methylene blue and the methylene blue-sulfonate complex enters the bottom chloroform layer resulting in an increasing blue intensity.
UV VIS is an older technology and is not as used as often as HPLC.
The Role Of The Cleaner Manufacturer
Cleaning validation is a critical part of the manufacturing process in regulated industries. Validation methods must be developed, planned and included in the production method. Since cleaning validation methods are unique to the cleaner used, it makes sense to expect the manufacturer to provide support. By relying on the cleaner manufacturer for detailed validation methods, manufacturers in regulated industries can focus their resources on manufacturing and product development, saving a great deal of time and money.
Download IPC’s validation overview or contact our technical specialists for detailed validation methods.