FDA Cleaning Validation Protocol

The FDA cleaning validation protocol is an integral part of cleaning all equipment used in pharmaceutical manufacturing processes, including equipment used to manufacture sterile drug products and non-sterile final drug products. It should be noted that cleaning validation for pre-production equipment requires greater stringency, including documented verification and validation activities. The purpose of cleaning validation in a drug manufacturing environment is to ensure that minimum levels of cleanliness are being met so as to avoid the possible contamination of a drug product. 

The FDA recommends that companies whose products require sterilization and/or high-level disinfection should validate their cleaning and thoroughly investigate their facilities for residues before putting them into use in order to prevent cross-contamination and ensure good manufacturing practices. The validation process requires manufacturers to establish criteria for the cleaning process, the number of tests that must be done to qualify a process, and testing methods. 

What is cleaning validation and how is it done?

Validation is the demonstration that the cleaning and disinfection procedure produces a processing cycle that does not reduce or remove the bioburden to an unacceptable level or adversely impacts any other aspect of device performance, and there is evidence that it will achieve this for at least one reprocessing cycle. Validation should be performed by an individual who understands the validation process, is competent to judge reprocessing results, and has full authority for implementing corrective actions. This process must be conducted under conditions similar to those expected during routine use. If there are any deviations from normal procedures (i.e., cleaning or disinfection cycle time, temperature, chemical concentration), they must be identified and justified.

The FDA recommends a minimum of three tests on three consecutive days with a time interval between each test. Each test should include two samples from locations where bacteria can survive in some machine components or fittings, such as air or cooling water supply line, a water coil, or an area where hydraulic fluid accumulates. The first sample should be taken immediately before the cleaning process, and the second one should be taken after the complete drying of all components or fittings. The intervals between each test are designed to ensure that no residues are left behind during the drying period.

The validated cleaning and disinfection procedure should include:

  1. A list of all device components or items to be reprocessed. 
  2. Description of the cleaning protocol including environmental conditions (room/automotive type humidity recirculating system, etc.), cycle time, pressure or vacuum level, temperature, the concentration of the cleaning agent(s), buffers, etc.
  3. Procedures for performing or witnessing all critical steps in the reprocessing procedure are required except where it is impractical to witness a particular step by personnel other than the person actually performing that task.

The FDA recommends that all reprocessing be conducted in a validated environment so the exact conditions used during process development are duplicated. The recommended cleaning, disinfection, and sterilization validation protocol are designed to provide performance information under conditions most likely to occur when the device is actually reprocessed.

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