ICH Q7 - Good Manufacturing Practice Guide for Active Pharmaceutical Ingredients 18.3: Use closed systems or controlled environments for aseptic additions and open manipulations, monitor critical culture parameters, clean and sterilise equipment and media, and detect, assess and record contamination

What does 18.3 require?

Aseptic additions (cell substrates, culture media, buffers, gases) should use closed or contained systems wherever possible, with controls and procedures to minimise contamination where inoculation, transfers or additions are made in open vessels. Where microbial contamination can affect quality, open manipulations should take place in a biosafety cabinet or similar controlled environment, by suitably gowned staff taking special care with cultures. Critical operating parameters such as temperature, pH, agitation, gas addition and pressure should be monitored for consistency with the established process, along with cell growth, viability and productivity where relevant (some may not apply to classical fermentation). After use, equipment for cell culture needs cleaning and sterilising, fermentation equipment cleaned and sanitised or sterilised as appropriate, and media sterilised before use where needed. Procedures should detect contamination, set the response, assess product impact and decontaminate equipment for reuse; foreign organisms should be identified and their quality effect assessed where needed and considered in disposition. Contamination events should be recorded, and shared multi-product equipment may need extra testing after cleaning between campaigns.