GaryM,

 

Anyone who has worked in pharma mfg over time, whether large pharma or small pharma, including biotech and now cell therapies, will have stories about mfg processes which either tipped into reproducibility failure due to an unforeseen subtle change or experienced significant improvement of some sort due to something subtly similar.  The best approach is to have experienced eyes on the process starting from development through mfg.  Development of the process should provide a strong framework of testing and characterization to provide confidence in it.  When things happen new learning adds to the knowledge.  In a case such as NWBO I think it is key to keep in mind they have been mfg this product for several years now over quite a number of patients, in the trial and outside of it.  They have successfully transferred the mfg process multiple times which shows me they have a good working knowledge of the process variables which are most critical to product quality and process control in addition to a robust knowledge of the risks to a successful transfer.  

 

I don't have concerns about their ability to mfg this product and I am not sure why that is an issue other than startup of commercialization is always a general concern, but, generally due to size scale up, which mostly does not exist here.  This is a single patient mfg batch size process, so, the largest variable of scale up is mostly eliminated. Comparison to small molecules is good to understand but only partially applicable.  I was involved with a tech transfer of a small molecule drug where we had to replicate a 100 year old granulator via fabrication and remove and re-install a dryer from the sending plant to the receiving plant, all so that critical mfg conditions were replicated.  It succeeded.  My point is that NWBO is as reasonably ready as a company can be in a situation like this based on their experience base of mfg this product.   They appear to me to be ready to increase their operating capacity at their mfg sites.  It is the experience they have with this product mfg process that would give me confidence in their readiness, which is a good by product of such a long trial as this one.