4.1.3 The cleaning validation protocol should include:

• the objectives of the validation process;

• the people responsible for performing and approving the validation study;

• the description of the equipment to be used, including a list of the equipment, make, model, serial number or other unique code;

• the interval between the end of production and the commencement of the cleaning procedure (interval may be part of the validation challenge study itself)

  - the maximum period that equipment may be left dirty before being cleaned as well as the establishment of the time that should elapse after cleaning and before use;

• the levels of microorganisms (bioburden);

• the cleaning procedures (documented in an existing SOP, including definition of any automated process) to be used for each product, each manufacturing system or each piece of equipment;

• all the equipment used for routine monitoring, e.g. conductivity meters, pH meters and total organic carbon analysers;

• the number of cleaning cycles to be performed consecutively;

• the sampling procedures to be used (direct sampling, rinse sampling, inprocess monitoring and sampling locations) and the rationale for their use;

• the data on recovery studies (efficiency of the recovery of the sampling technique should be established);

• the analytical methods (specificity and sensitivity) including the limit of detection and the limit of quantification;

• the acceptance criteria (with rationale for setting the specific limits) including a margin for error and for sampling efficiency;

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• the choice of the cleaning agent should be documented and approved by the quality unit and should be scientifically justified on the basis of, e.g.

  - the solubility of the materials to be removed;

  - the design and construction of the equipment and surface materials to be cleaned;

  - the safety of the cleaning agent;

  - the ease of removal and detection;

  - the product attributes;

  - the minimum temperature and volume of cleaning agent and rinse solution; and

  - the manufacturer's recommendations;

• revalidation requirements.