Replies to post #196736 on NorthWest Biotherapeutics Inc (NWBO)

[exwannabe]

In the Q&A you link, "similarity" is in reference to considering what the Orphan protect covers.

In this case, if DCVax-L was to obtain approval for glio, then no other whole tumor lysate DC would be approved for glio for 10(?) years. OTOH, a DC agent like Inova's or CLDX's could be.

So if somebody wanted "their" version of DCvax-L approved in glio, no luck. And changing to a closed system would not be sufficient to make their'e different.

I am not sure where you are going with this, but this is far different from the manufacturing lock-down needed to insure a product is "the same".

The issue with manufacturing changes is that we have no way of knowing what something like DCVax actually is. Biologics are defined by the steps and checks that make them. Change those steps, and you are changing the product.

[sentiment_stocks]

Ummmm... wow?!

It is stressed that not all changes to the manufacturing process can qualify as a change in manufacturing technology. For example, a change in manufacturing process (e.g. cultivation of cells in an open system vs. a closed system; change in the number of cell passages) or a change in equipment (e.g. upgraded bioreactor) generally cannot support a finding of non-similarity.

That passage covers a lot of ground. Ground that we’ve been covering a great deal recently.

Just curious... would number of cell passages describe the TFF process?

[doingmybest]

Lykiri,

Like a lot of issues discussed here it is quite difficult to be definitive with such partial knowledge of the facts. However the principles of how to prove similarity apply to all types of products. The mfgr has to ensure through science and testing that safety, efficacy, purity and quality are not negatively affected. You may already know this. We know they have introduced TFF into the mfg process. TFF is mostly an efficiency improvement but it can, like all changes have additional desired or not desired effects. In this application it is probable that it is a significant efficiency improvement due to the difficulty in attaining the appropriate type of DC's. We know they hired the German technology group to optimize the mfg process. We don't know what all was changed here. My guess is that the majority of work was focused on process definition and not changes per se. This means the work was focused on defining the appropriate ranges for each critical process parameter through testing. This work is typically started prior to P3 but often mostly done concurrent with P3 clinical trial activity due to mfg preparedness activity. I'm not aware of any major differences introduced to their processing technology. I don't see anything of concern here. It is always good to have guidance from RA's to provide structure to technical tasks and to technical discussions with them. There is no reason not to believe their technical people at Cognate and elsewhere that they employed are not expert at honing this process and that their regulatory people are not expert at knowing how to manage the info to the RA's inside and outside of clinical activity.

[Doc logic]

Lykiri,

The guidance states that closed vs open system is not sufficient to itself create a dissimilarity. By indirect inference this means that this change is not sufficient to cause a change in product eqivalency in and of itself either. What all the bears are having a hard time with is that the product cellular characteristics are not being changed by what NWBO seems to have done. They do appear to have made changes that create greater purity and balance within each vaccine of desirable cells created from the same original maturation/activation process. This is ENCOURAGED by regulators as previous posts of non binding guidance strongly suggests. Les is correct (this is for exwannabe and others).. END PRODUCT CELLULAR CHARACTERISTICS HAVE NOT CHANGED FROM THOSE CREATED UNDER THE ORIGINAL PHASE 3 IND. Best wishes.

[flipper44]

More patent protection in the first bolded paragraph, clinical trial equivalency* basic assumption (in spite of possible TFF addition) in second. That's what it means to me, fwiw. IMHO



*One might argue the blended Journal publication was produced to substantiate this assumption. (Both published in May)