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Sp being chiselled by the day drones aided and abetted by the usual Micky &Minnie
I did some further research on this including the updated document provided by Ndn71.
Batch size:
Both the EMA and FDA have a 10% rule meaning the validation batch size should be at least 10% of the commercial production batch size. Based on RM’s comments of 100k treatments per month that would equate to 10k treatments or 140k doses. (I’m ignoring the 100k validation batch size (measured in doses) as that’s less than what RM alluded to and the Regulatory requirement states ‘greater of 10% or 100k)’.
Number of batches:
In my earlier post I mentioned three batches, but that’s based on old (FDA) language. The FDA does not specify the minimum number of batches while the EMA seems to require data on a minimum of three batches. The number of validation batches will be dictated by the required confidence level while achieving statistical significance.
Manufacturing partners & combinations:
We know Akron and Catalent are part of the supply chain. Based on the Investors Chronicle article we have Thermo Fisher on board for fill finish and seem to be retaining the relationship with Rentschler. Are we testing each of these combinations? Probably not, but I guess we would at least test a combination of Akron & Catalent and Akron & Thermo Fisher. I might be wrong on the latter – just have a hunch TF was brought in as a result of ACTIV-2 and so it would need to be tested
For simplicity I assume commercial scale batch would equal that of a month’s production i.e. 100k treatments. As to how much have we manufactured - good question - if this assumption is correct probably about 30k treatments. Could be wrong.
Fruitsnveg – re ACTIV-2, I remember looking at it earlier this year and as part of the application process Synairgen had to provide evidence that it can successfully upscale production. I have not seen anything to suggest batch validation procedures have been amended specifically for ACTIV.
Thx for your input Fruitsnveg & Ndn71.
Disclaimer: 1) This aims to address the question on potential current production levels as part of the supply chain validation process and not future commercial production.
Page 17 section V(A)(1) https://www.fda.gov/media/70949/download
Pages 5/6 section 5.1 https://www.ema.europa.eu/en/documents/scientific-guideline/guideline-process-validation-finished-products-information-data-be-provided-regulatory-submissions_en.pdf
https://www.investorschronicle.co.uk/news/2021/01/14/with-vaccine-roll-outs-underway-what-does-the-future-hold-for-covid-19-treatment/
Good stuff Ndn71.
Matterhorn,
I have to say, the 100,000 figure I give below might be accurate in our case, or it might not. Like I said, those guidance notes may have been updated for the Pandemic. A guesstimate at best. The ideal would be to have a Chemical /Pharma Manufacturing bod comment on this (there were a few on the BB in 2020 I think?), they would be better placed to comment on it than I.
BTW, I concur with the 100k per month figure, that too was my understanding.
Fruitsnveg - that’s brilliant. Thx!
In addition it seems you need to produce at least three batches as part of the validation process. That means in a best case scenario we could be looking at 300k doses manufactured which is roughly 21.5k treatments.
Doc - the animation didn’t say whether it was per month, but RM stated 100k treatments per month. Numis’ broker note was also based on 100k per month. It would be right to conclude that’s what the animation was referring to.
Matterhorn,
"If it’s their aim to manufacture circa 1m doses per month then the question would be how much (i.e. doses) should they produce as part of a test run or runs to give them a sufficient level of confidence that they can pull off 1m doses per month."
Below is a link to an old "Note for Guidance on Process Validation" produced by the EMA back in 2001, where it states that 'pilot' batches (which, if you read the definition in pages 3/4 of the link below, seems to be what RM was talking about) should be 10% of production scale or 100,000 doses whichever is the larger. Pages 3 & 4 are where you need to look. I cannot find a more recent version if one exists, but I cannot imagine the standard pilot batch figure would have changed in 20 years. Up until recently the pharma world was somewhat of a dinosaur I imagine. It could however be that the FDA/Warp Speed guidelines of 20/21 stipulate a different amount due to the urgency of this pandemic, but I have not yet been able to wade through sufficiently to find a batch figure in their guidance. That's not to say it's not out there, I just have not found it, yet.
https://www.ema.europa.eu/en/documents/scientific-guideline/note-guidance-process-validation_en.pdf
The MRC animation stated 1m doses which equals about 71.5k treatments per month.
100k?
The reference I made to RM’s comment which was ‘done to validate commercial scale’ could give an indication as to potentially how much product they may have produced. As I mentioned, it’s open for interpretation. What’s worth bearing in mind is that, if it’s their aim to manufacture circa 1m doses per month then the question would be how much (i.e. doses) should they produce as part of a test run or runs to give them a sufficient level of confidence that they can pull off 1m doses per month. I don’t know the answer to that, although I would think it has to be a fair bit.
Of course we won’t have huge quantities and we shouldn’t have yet, but what I was trying to convey is that I’d say or think that we have a decent amount of product on the shelf already.
Doc - you’re right I didn’t add that very last sentence, but it was deliberate. I wanted to focus on manufacturing done as part of process validation and the potential quantities produced as a result.
Part of the process validation will be the fill & finish by Catalent. So maybe someone with manufacturing experience could share with us what they think the minimum quantities required by Catalent would be to do a such a test run(s).
Interesting how much more considered and constructive this board is after a certain time of day ...
Manufacturing featured quite a bit over the past day or so. The best way to address the topic would be to refer to Richard’s comments during the AGM's Q&A session back in June. That is of course in the absence of the soon to be released interim results.
Forward to 11.50 of the video
https://www.lsegissuerservices.com/spark/Synairgen/events/1cd87eb6-5e01-4e1a-b3bd-f8288bbb6b5b
This is what RM said:
- They have manufactured multiple drug substance batches i.e. interferon beta; and
- several drug product batches which are now undergoing stability studies.
- This is done to validate commercial scale end to end manufacturing process.
The last bit of the answer ‘validate commercial scale’ is potentially open for interpretation. Does it mean …
1) they are producing (a one off) at commercial scale to test the manufacturing process or
2) it’s not at commercial scale, but (much) smaller batches to ensure commercial scale would be possible?
Either way it would not be wrong to deduce from this that there are potentially quite a bit of drug sitting the shelve ready for distribution. I would be particularly keen on knowing to what extend Thermo Fisher is involved which was referenced in an interview by Investors Chronicle in Jan 2021. This is the only time the company mentioned TF's involvement. Is it maybe linked to ACTIV-2 on request of the US Gov, hence no word about it.