Reg, it's their document. It'll mean exactly what they want it...

Reg,

it's their document. It'll mean exactly what they want it to mean. I'm not aware of any published interpretations of this phrase in the SOPP, but IMO 'final' means 'as a last (or v close to last step) in the process of manufacture' i.e. a test which does not disturb the prior process data or the conlcusions to be drawn from them & so able to be considered within the lesser 2 month period. Just my view.

This is the problem with having to 'demonstrate' things - at the end of the day, FDA will make up it's own mind when it's had/got enough i.e. to admit that it's been 'demonstrated'. All this rubbish about 2 trials, and has to be ramdomised etc doesn't stack up against the FDA's willingness to approve some drugs/ biologics on the basis of a PhI/II trial, perhaps still in process, poor correlation of potency withoutcomes & so on.

Yet that's exactly what happened with tisagenlecleucel (Kymriah) in 2017 - see my earlier post above. e.g. from the article reviewing CTP approvals in the US and the wild variances in approval-supporting evidence, consider this graph.

Count the number of approvals based on single-arm trial designs - with all their flaws bleated & moaned so self-righteously about by FDA personnel at ODAC - and remember there was no published FDA "guidance" on CTPs pre-September 2023 even stating that a single trial might be good enough for a CTP approval:



...and this from the FDA's very own 2017 Briefing Document to ODAC (Vote 10-0 in favour of approval) on Kymriah:


So, "difficult to correlate" isn't a problem for the FDA when it doesn't want it to be a problem.

It would be easy to get angry with the apparent hypocritical behaviour of the FDA, especially with their use of the mantras re acting 'in the best interests' of the children.

But I'd rather get approval.

IMO FDA have (internally) reached that point of 'demonstration' with the data they already have received from MSB, and which they've had for analysis & which I think we've been chatting with them about for since we got their formal "responses" i.e. on 26 March this year.

Just my view of things.

Cheers
GLTA(LT)H