Cleaning Validation

Cleaning validation is important to prevent (cross) contamination of the products during manufacturing. All types of contamination must be identified (during the Risk Analysis). Most often, contamination happens due to change of material on the machine, and the machine must be cleaned before starting the new production run.  This cleaning process must be validated. Cleaning Validation follows the same steps (IQ, OQ and PQ) as process validation, but the content of these steps differ. Below some possible steps are described.

 

Types of Sampling Methods

The way the cleaning must be validated is not defined, but is is generally accepted in the industry that there are two types of sampling methods for cleaning validation:direct and indirect.

  • Direct sampling for cleaning validation is also known as the swab method, where a sterile material is systematically rubbed across a surface to be analyzed for the presence of residue.
  • Indirect sampling for cleaning validation is often called rinse sampling, where a solvent like water is rinsed in a specific area of clean surface and tested for traces of contaminants.

Types of Cleaning Methods

There are many types of cleaning methods, and it is very much depending on your process. Here is a list of possible methods.

  • Clean-in-place Method – normally using fixed or rotating spray devices with a wash tank, recirculation pump, and associated piping
    • Purging –  Form of Clean-in-place method to push out one component with another.
  • Clean-out-of-place Method – often used for automated parts washing through cabinet or tunnel washers with cleaning, rinsing, and drying cycles.
  • Immersion Method –  either agitated, where a cleaning agent in a process vessel is mechanically stimulated to achieve a cleaning effect, or static, where the process vessel is merely soaked with the cleaning agent
  • Ultrasonic Washing – typically works better for intricate parts such as filling needles as it involves a tank equipped with ultrasonic transducers to induce cavitation.
  • High-pressure Spraying – dislodges any residues on the surface through high-pressure, continuous, and directed water or cleaning solution.
  • Manual Cleaning – usually the most difficult cleaning method to validate; includes the three most common techniques: wiping, sink brushing, and equipment brushing

Acceptance Criteria

Accurately setting the acceptance criteria for the limit in cleaning validation is crucial to determine the study results. To better evaluate whether or not cleaning methods are effective, cleaning validation acceptance criteria can be generally categorized into three various testing parameters:

  • Physical Criterion: a visual inspection of the equipment should reveal that there are no particulate matters or residues.
  • Chemical Criterion: a maximum number of ppms (parts per million) of a product may be detected in another product.
  • Microbial Criterion: no more than x CFU (colony-forming units) for bacterial counts (total or per surface area) and no more than y CFU for molds in a sample.

Required documents

  • Written standard operating procedures (SOPs) for equipment cleaning processes that address different scenarios (e.g. one process for different batches, different processes between product changes, etc.).
  • Written cleaning validation procedures, including who is responsible for performing and approving the validation study, the acceptance criteria, and when re-validation will be required.
  • Written cleaning validation protocols for the inspection of each piece of equipment that address common issues (e.g. sampling procedures, analytical methods, etc.), conducting the validation according to the protocols and documenting its results.
  • Final cleaning validation report stating whether or not the cleaning process for a specific piece of equipment or manufacturing system is valid.