Understand ICH Q7 S6

Is it expected that campaign manufacturing be addressed in cleaning validation? 

Yes. The cleaning validation section [ICH Q7, 12.7] does not specifically address campaign manufacture. However, sections [ICH Q7, 5.23, 8.50] set forth the expectations that equipment be cleaned at appropriate intervals (e.g., time or number of batches) to prevent build-up and carryover of contaminants so that they do not adversely alter the quality of the API. The appropriate interval is confirmed during cleaning validation. 

At product changeover, are both visual examination and analytical testing necessary to verify that equipment is clean? 

Appropriate cleaning validation verifies that the cleaning process is effective. During cleaning validation, both visual examination and analytical testing should be used to verify cleaning effectiveness [ICH Q7, 12.72-75]. Once the cleaning process is validated, routine monitoring of cleanliness of equipment at product changeover should include visual inspection [ICH Q7, 12.76]. Frequency of analytical testing to verify ongoing effectiveness of the validated cleaning process is determined by the API manufacturer using a risk-based approach. In situations where the cleaning process is not yet validated, both visual examination and analytical testing are expected. For APIs with a retest date, [ICH Q7, 6.13] states that records related to production, control and distribution should be retained for at least 3 years after the API batch is ‘completely distributed’, which is understood as the complete distribution of the entire batch of the API by the API manufacturer to the next party in the supply chain. In the case of APIs handled by agents, brokers, traders, distributors, repackers, and relabellers [ICH Q7, 17], ‘completely distributed’ refers to distribution of the received quantity of the batch of API. The intent of ICH Q7 is to retain records for the period of time that the API could be on the market in order to investigate any problems and/or product complaints. Based on accepted industry practice at the time ICH Q7 was written, it was not anticipated that a manufacturer would set a retest date longer than 3 years. However, the use of ‘at least three years’ in this section of ICH Q7 covers longer record retention periods, which is in alignment with the basic GMP principle and/or regional requirements that records be retained for the entire period the material is available on the market. It is good industry practice to consider retaining records for the period of time the drug product(s) in which the API was used may be available on the market.