15th of April 2021

Toxicological assessment continues to gain acceptance for cleaning validation

WHO publishes decision on setting acceptance criteria for cleaning validation


The WHO Expert Committee on Specifications in Pharmaceutical Preparations , as announced on March 25, 2021, has decided to require toxicologically based limits for cleaning validation in the future. The procedure for setting the limits has already been published. The guideline for performing cleaning validation will be adapted.

The WHO follows the paradigm shift initiated by the EMA in 2015. Health-Based Exposure Limits (HBELs) have to be used as acceptance criteria in cleaning validation. In the meantime, the PIC/S has published a corresponding guideline in 2018, but has left it up to the participating authorities whether they implement the guideline in their area of responsibility.

In the first step, the Permitted Daily Exposure (PDE) must be determined on a toxicologically justified basis by a qualified expert. For this purpose, all available data have to be evaluated and, if necessary, further data have to be collected in studies. The determination of the PDE has to be based, if possible, on the NOAEL value(s) (No Observed Adverse Effect Level). The lowest calculated PDE value is decisive.

Based on the PDE value and information on the batch size, possible dosage strength of the drug and contact area, the MSC (Maximum Safe Carryover) and MSSR (Maximum Safe Surface Residue) have to be calculated for the individual product changes.

Valicare GmbH (subsidiary of Syntegon Technology GmbH) has planned and implemented cleaning validations based on PDE values successfully in several projects. We have all necessary documents and specifications available to enable you to implement quickly toxicologically based limits in cleaning validation.

For more information about our GMP-compliant cleaning validation services, please visit our homepage. 

Author: Dr. C. Börger, Senior GMP Consultant, Valicare 

Ellen Sons Brinkmann

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Dr. Ellen Sons-Brinkmann
Tel: +49 69 153 293 709
Mail.: ellen.sons-brinkmann@valicare.com