Contract givers should either provide a full HBEL assessment to contract manufacturers or provide the data to allow the contract manufacturer to conduct the HBEL assessment.

In either case, the HBEL assessment, including data references and relevant experts, should be available on request during the manufacturer’s inspection.

Although the EMA guideline (EMA/CHMP/CVMP/SWP/169430/2012) may be used to justify cleaning limits (as per Introduction paragraph 3), it is not intended to be used to set cleaning limits at the level of the calculated HBEL.

For existing products, the manufacturer’s historically used cleaning limits should be retained. They can be considered alert limits provided that when taking cleaning process capability into account, they provide sufficient assurance that excursions above the HBEL will be prevented. A similar process should be adopted when establishing cleaning alert levels for products introduced into a facility for the first time.

Results above the alert cleaning limit should trigger an investigation and, where appropriate, corrective action to bring the cleaning process performance within the alert cleaning limits. Repeated excursions above the alert cleaning limit will not be considered acceptable, where these indicate that the cleaning method is not in control. Recognised appropriate statistical methods may be used to determine whether the cleaning process is in control or not.