Guidance on aspects of cleaning validation in active pharmaceutical ingredients palnts

ACTIVE PHARMACEUTICAL INGREDIENTS COMMITTEE (APIC) initially updated in 2014 by the APIC Cleaning Validation Task Force on behalf of the Active Pharmaceutical Ingredient Committee (APIC) of CEFIC.

A revision of the guidance document was done in 2016 to bring it in line with the European Medicines Agency Guidance on use of Health Based data on setting health-based exposure limits for determining safe threshold values for the cleaning. The main changes were introduced in Chapter 4, Acceptance Criteria.

A further revision has now been done in 2018 - 2019 to address comments received from industry, to align further the guidance with the EMA Q&A2 on use of Health Based Exposure Limits (HBELs) and published articles on use of HBELs. 

The subject of cleaning validation in active pharmaceutical ingredient manufacturing plants has continued to receive a large amount of attention from regulators, companies and customers alike.

The integration of Cleaning Validation within an effective Quality System supported by Quality Risk Management Processes should give assurance that API Manufacturing Operations are performed in such a way that risks to patients related to cleaning validation are understood, assessed for impact and are mitigated as necessary. 

It is important that the requirements for the finished manufacturing companies are not transferred back in the process to active pharmaceutical ingredient manufacturers without consideration for the different processes that take place at this stage. 

For example, higher limits may be acceptable in chemical production compared to pharmaceutical production because the carry-over risk is much lower for technical and chemical manufacturing reasons.

The document reflects the outcome of discussions between APIC member companies on how cleaning validation requirements could be fulfilled and implemented as part of routine operations.

In addition, APIC has aligned this guidance with the ISPE Risk MaPP Guide3 that follows the Quality Risk Management Processes as described in the ICH Q9 Guidance on Quality Risk Management. 

The criteria of Acceptable Daily Exposure (ADE) or Permitted Daily Exposure (PDE) are recommended to be used by companies to decide if Dedicated Facilities are required or not and to define the Maximum Acceptable Carry Over (MACO) of API’s in particular, in Multi Purpose Equipment.

APIC cleaning Validation Guidelines