During the purification process of some recombinant proteins, affinity chromatography techniques with monoclonal antibodies are used. It’s well known that leakage of antibodies frequently expected that would contaminate the API. How can this possible contamination with another biologically active entity be considered under control in order to validate the process? Is this procedure regarded by the Q7A as an appropriate procedure since it incorporates contaminants into the API production process?

I wouldn’t consider this to be inappropriate under Q7A. It’s certainly a process contaminant, but it would be expected and, as part of your monitoring program, you would evaluate the API for the monoclonal antibody that potentially could be coming off your affinity column. Moreover, as part of the column cycle, you should evaluate the lifespan of the column. That is, you should be periodically monitoring and know the lifespan of the column. You would be monitoring its use, and therefore, you will minimize the potential for what would be viewed as cross-contamination with the monoclonal antibody coming off the column. I agree with that completely, and I would add that typically, phase III studies sort of define the level of antibody contaminant that is tolerable because these studies showed that the product was safe and effective. So as long as you don’t exceed these levels in the marketed material, that’s typical an acceptable level of contaminant, then the trick is to make sure that the process does not exceed these levels. It could be validated as Jay mentioned always not to exceed those levels throughout the intended life of the column. Column lifespan is something that would be looked at on inspection. So if you have got a number of different columns in addition to an affinity column that is something that would be key for inspection because we often find it is lacking in the validation or prospective validation of the facilities.