Hello,

1) ISPE: Guide: Cleaning Validation Lifecycle - Applications, Methods, & Controls.

Guide: Cleaning Validation Lifecycle - Applications, Methods, & Controls | ISPE | International Society for Pharmaceutical Engineering. (For North America regulatory compliance.)

2) New changes to cleaning validation requirements (For European compliance)

The following documents explain the new requirements on cleaning validation:

• The EMA revised its guideline “on setting health based exposure limits…”, applicable as of June 2015 (3). Active or detergent residue limits (Maximum Acceptable Carry Over – MACO) have to be assessed through health-based limits using the Permitted Daily Exposure (PDE). The PDE represents a substance-specific dose that is unlikely to cause an adverse effect if an individual is exposed at or below this dose every day for a lifetime. The PDE is calculated using the NOAEL (No Observed Adverse Effect Level), the body weight and five uncertainty factors, e.g., toxicological and pharmacological clinical or non-clinical data. The PDE has to be assessed by an experienced toxicologist. The Lowest Observable Effect Level (LOEL) would be acceptable to use if the NOAEL data could not be determined (4). Finally, the toxicological data has to be part of the worst-case product identification assessment, except if the active residue is known to be degraded and may become pharmacologically or toxicologically inactive.
• The EU GMP annex 15 “Qualification and Validation”, applicable as of the 1 October 2015 (5), requires cleaning validation to be based on a scientific and risk based approach. As a result, “visually clean only” criteria is no longer acceptable. The number of validation runs required may be determined through a risk assessment justification. To demonstrate robust cleaning, sufficient data is to be captured through continuous monitoring or on-going verification. The ongoing verification frequency will be driven by the quality and business risk assessment results. The Guideline also requires that the active residue limit is calculated using toxicological data (health based limit). As such, the worst case residue should be determined based on solubility, cleanability, and potency, including toxicological data review. Finally, dedicated equipment should be considered when a cleaning process is ineffective in order to remain below the calculated limit.

When it comes to cleaning validation for a specific process where you need to outline (equipment/product/) in a protocol you will need to contact firms of consultants that do this type of work.

You will not be able to get a protocol for your process unless you pay for the service of having someone with experience in cleaning validation to write it up for your process.

Hope that helps.