Understand ICH Q7 S5

To what extent can quality risk management be used in establishing appropriate containment measures to prevent cross-contamination? 

The principles of quality risk management [ICH Q9, Annex II.4] should be applied to the design of buildings, facilities and controls for the purpose of containment, taking into consideration the pharmacological/toxicological/chemical/biological properties of the raw material, intermediate and/or API to be handled or manufactured. Appropriate containment measures and controls [ICH Q7, 4.42] include but are not limited to the following: • Technical controls (e.g., dedicated production areas, closed/dedicated HVAC system, closed manufacturing systems, use of disposable technologies, design of facility and equipment for containment and ease of cleaning) 

Procedural (organisational) controls (e.g., cleaning, personnel flow, environmental monitoring and training) Monitoring systems are important to check the effectiveness of the containment controls. 

For dedicated equipment, is ‘visually clean’ acceptable for verification of cleaning effectiveness, (i.e., no expectation for specific analytical determination)?

Visually clean’ may be acceptable for dedicated equipment based on the ability to visually inspect and sufficient supporting data from cleaning studies (e.g., analytical determination to demonstrate cleaning effectiveness) [ICH Q7, 12.76]. Equipment should be cleaned at appropriate intervals (e.g., time or number of batches) to prevent buildup and carryover of contaminants (e.g., degradants or objectionable levels of microorganisms) so that they do not adversely alter the quality of the API [ICH Q7, 5.23, 12.7].

Should acceptance criteria for residues be defined for dedicated equipment? 

Yes. Regardless of whether equipment is dedicated or not, it is expected that acceptance criteria for residues be defined and that the equipment be cleaned at appropriate intervals to prevent build-up and carry-over of contaminants. Intervals can be based on number of batches, product change-over, time, etc. [ICH Q7, 5.22, 5.23, 5.24, 5.25, 8.50]. Cleaning intervals and acceptance criteria should be established based on an understanding of the process/reactions/degradation, taking into account solubility, potency, toxicity, etc. Establishment of acceptance criteria does not necessarily imply sampling and testing after every cleaning. Visual inspection of equipment for cleanliness is an expectation of [ICH Q7, 5.21]. Where validation data has confirmed effective cleaning, cleaning procedures should be monitored at appropriate intervals [ICH Q7, 12.76].