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Just some more speculation following Monday’s RNS, why it was issued, how to interpret it, what it has to do with the recent request to tender, etc.

First why no mention of Cytiva? It’s been suggested BBI have in some way taken over their role. But go back to the Q&A after the September Interims. The fact AS chose this as the first thing to answer surely tells us Cytiva has a key role. This is how he explained it all fitting together:
Q1: "... please give an explanation of Cytiva’s role in the manufacture of the rapid antigen test.”
Answer: “That’s a good question, which allows me to clarify… So Cytiva are a materials company, they manufacture the materials to make the strip … they supply the finished nitrocellulose strip, not the finished IVD. So the manufacturers who supply the finished IVD are the likes of BBI Solutions and Abingdon Health… It’s really a process of raw materials from Cytiva and Avacta… So we have partners who do the strip manufacturing, and partners who do what’s called the kitting, who put the kits together and then obviously the logistics of shipping those out”

Cytiva seemed to get singled out by some as the culprit in the switch from spit to swab. I am not sure. Equally it could all go back to the mad panic March onwards when PPE, reagents, face masks, swabs and all the rest of it were virtually unobtainable. Then remember the five pillars - the fifth, research, included building up a sovereign diagnostics capability. So Avacta come up with a super spike binding very specific affimer reagent and partner with Cytiva who suggest or are persuaded the use of saliva is doable rather than the use of swabs, sourcing of which being from overseas would at that time have been problematic?

Through into late summer there is a reluctance to regard PCR as anything other than the gold standard. Dr Mina and others helped change that and the diagnostics powers that be (Porton Down, Prof Bell, etc.) decide LFTs could be OK but that spitting into a pot is unhygienic, saliva is subject to cheeseburger contamination, etc. (All conjecture on my part – which is what these threads are about?)

So by now swabs are becoming more readily available maybe now we can make them in the UK - like it seems we may now be making quantities of face masks. In his video on Monday AS says the issue with swabs has been simply sourcing but now he says “ we have done extensive work and we have more than one source – high volume source – in place”
So surely the government is just as likely behind the switch to swab as Cytiva. Also from the governments point of view the uniformity of messaging - education as to modality of use - that comes with using swabs in both Avacta’s and in the Innova test may also be an attraction?
But why was BBI singled out in last Mondays RNS and no mention made of Abingdon? Well for one BBI are the lead manufacturer. But is there something else? continued...

Very good article, though a few weeks old. It deals well with the strategies that will be necessary for vaccination and re the need for testing in the longer term, about which it starts by saying this this:

You need low case numbers to track and quarantine everyone infected, and UK numbers are currently too high. But vaccination should drive case numbers down to where containment becomes practicable. “We need to all become South Korea as quickly as possible,” says Joshua Gans of the University of Toronto, author of Economics in the Age of Covid-19.

Bodes well for building up delivery throughout next year of a gold standard LFT!

Dogs80... To me it was a strange RNS to put out, I felt like a lot was being held back and it was only put out for a reason, I don’t think spit is over, I think there more to it than it just didn’t work out.

There is one clear reason for the saliva to anterior nasal swab switch RNS yesterday. Who knows whether we are in the running in this current £512m tender, but if we are awarded something 16th Dec it would come as a shock on the day to find out we were being awarded a swab contract when everyone believed we were about to launch a unique saliva test. Without yesterday's announcement we could not be in contention.

A key point well made by Michael Mina in this tweet:

This paper also does not look at symptomatic vs asymptomatic use... But WHY??

Because the test DOES NOT CARE about symptoms. Clinical medicine cares. A public health test for contagiousness ONLY CARES ABOUT VIRUS presence

I wish @US_FDA could understand this

Sir John Bell said they have found about 6 LFTs with usable S & S with his validation being published tomorrow. He does not say clinical validation . I cannot see why pre BBI pilot samples e.g. produced by Cytiva, cannot have been included in his assessment, done maybe by Porton Down?

If such work has been going on I cannot believe AS would want to pre-empt Sir Johns statement and make mention of it in todays tweet, which they were clearly forced to put out by yesterday's sp drop. In fact a pedantic reading of AVCT's tweet today seems to leave wide open that possibility that Sir john has included the Avacta LFT in his validation work. AVCT's tweet refers to preparing for "the first clinical evaluation of the rapid antigen test", which clearly does not preclude some preceding S & S validation.

Poundcake - you say next up, the bid stats contract for Avacta.

This is something that I have always wondered about? Rather than being a massive order for Avacta, since they will not be supplying the end product - the LFD test kit - will not it rather be several massive orders for BBI, Abingdon and whoever else? Avacta will then obviously get a huge junk of revenue on the back of these orders. Clearly though Avacta will get all the kudos - ideally each LFD should be stamped 'Avacta Affimers Inside' ;-)

Surely there is another reason for the funnel being needed, as well as a pot, which is that by using these in combination it must be possible to get the user (particularly those self-administering) to mix a fairly precise and consistent proportion of saliva and buffer? Just swigging something and spitting in a pot would be hopeless in this respect and as pointed out an elf and safety nightmare.

Monkshood/Jaylarc - thanks, very interesting discussion. Looking at it another way however, would it not actually be fairly straight forward in practice for AVCT to deal with new emerging variants? Through April it took them a matter of weeks to identify the affimers appropriate to the then dominant strain. So presumably new affimers for any new variant could be very quickly identified and substituted for the original ones. On the one hand this sounds very simplistic. But I cannot imagine that the switching of affimers would make any difference to the dynamics of liquid flow in the device, wicking through the membrane, etc. And I doubt there would need to be any changes with the other reagents, buffers etc? Assuming the current approval process has all been completed, CE approval gained and the LFD in its initial iteration has been launched and is in use, then presumably the main work in switching to a new set of affimers would be limited to re-affirming S & S in another set clinical trials? Four weeks or so maybe? Always the optimist!

The role of Cytiva does seem to cause some confusion! It has been clear all along that they are the key partner - not BBI, Abingdon and others to come. I thought AS made this clear earlier. Cytiva, and formerly Whatman from whom much of Cytiva's expertise derives, is both a developer and manufacturer of the core test strip at the heart of the LFD assembly. AL said this earlier - he said he was pleased to have the opportunity to clarify their role - they will be producing all the nitro cellulose membrane material, which I imagine will be pre- laced with affimer and other reagents, although he did not spell this out. On one of his slides he explained the four parts to the overall process - production of affimers, production of the test strip, assembling the final kit - BBI, Abingdon and others not yet signed up - and finally logistics - distribution. I know what Cytiva do and they are an impressive outfit. cI cannot imagine they will have been responsible for any delays, perceived or otherwise.

Thanks. I'm wondering whether there will be an after hours announcement on Friday too. There was a brief mention in the D Tel a few days ago that Boris was due to speak Friday although saying it was to be brought forward - i.e. to yesterday. Could he still have something else to unveil!

That all fits together very convincingly but I am curious as to why the protocol dated 15th August was only released today? Any thoughts @Energyshares, anyone?

The interesting thing was that the contributors, who were clearly knew what they were talking about, recognised that the whole subject was totally baffling to non experts and that journalists and government ministers didn't have a clue what it was all about. The really interesting thing however was at the end when Prof Spiegelhalter said the whole thing about false positives didn't really matter anyway. I wish he had explained that!

Clearly as you say @PL75, AS is satisfied that specificity is of a very high order and that AVCT's affimer based testing is clinically impressive. But even with the best of tests there will be unavoidable false positives. I guess the way the authorities look at it is that the economic and societal downsides of a large number of false positives is far outweighed by the overall hoped for benefit - that mass testing will bring things under control pending roll out of a vaccine.

Way back at the start of the pandemic WHO's mantra was test, test, test. The political kudos that will flow from successfully introducing a simple, cheap almost instantaneous self mass testing device will be immense - a get out of gaol card for the government. I cannot see the false positive issue derailing this with prevalence rising again.

In yesterday's D Telegraph there was an piece about current forecasts of a significant increase in mortalities if something isn't done quickly - circuit breaking measures etc. - being proposed by the CMO and others. And then saying that over this weekend the government will be looking at all the options. In amongst it was a snippet that it had been decided Mr Johnson's announcement for next Friday is to be brought forward to Tuesday.

Interesting to speculate that next Friday's announcement (post the market close at 5pm on past similar occasions) would have included something on mass testing allowing AVCT to disclose where things are up to on the 28th? Or will something come out on Tuesday about both tightening the current restrictions further and mass testing.

Interesting week ahead!

@abdalina re "Rate of false positives is a function of prevalence and test specificity which is the biggest stumbling block currently to implementation..." Clearly a lot of false positives is not a good outcome. So is this an argument for not ramping up mass testing until or maybe only in specific hotspots (and maybe unless) prevalence is high? Or have I got the wrong end of the (test) stick?

@Timster and others. The fact the Cytiva release is from Amersham may possibly be an interesting pointer. Not only did GE Healthcare - now Cytiva - buy Amersham plc but of much more relevance they bought the 200 year old UK Whatman company - of filter and chromatography paper fame - well known to anyone that has worked in pretty much any sort of UK lab. Whatman now also now do lateral flow membranes (I am not sure how to post links on here but if this doesn't work look it up on the rather poor Wikipedia page for Whatman plc):

HTTPS://en.wikipedia.org/wiki/Whatman_plc

After Whatman was taken over their historic Maidstone works - paper mill - was closed and new facilities were established alongside those of Amersham International in Buckinghamshire.

As per others @Wild_Card, great post. I agree it is interesting to see so much attention being given to identifying those most infection - would this result in Cytiva being asked to adjust the sensitivity of the test strip? Very interesting article from the Minnesota epidemiologist too - Covid 19 here for the foreseeable and vaccines may not provide durable immunity. Which I assume means we may have to learn to live with the virus long term, which in turn would require continuing worldwide cheap self-testing? (PS I put the Telegraph text up because I realised you and others could be outside the paywall - and I hope you didn't stay up specially till 1.50 to reply!)

The relevant LFT bits from the Sir John Bell article - most of it is about vaccines, which is his speciality, he is a a top immunologist :

Currently, he says, scientists are trying to scale up what is called a “lateral flow test” so millions are available each day.

These 15-minute tests would detect infectivity rather than diagnose Covid in all its forms, and so would have to have much less sensitivity.

Within a few weeks, Sir John says they will likely have more idea over how much of the virus the test will need to detect to pick up infectious people. “Say you end up with a sensitivity of 70pc or 80pc, the people who you wouldn’t pick up are the people with very little virus in their nose and mouth.”

“I’m not going to say we’ve got one for sure, but we’re pretty close and over the next few weeks, we’ll have a pretty good idea of where we are.”

Then, everything will rest on getting the tests manufactured at scale. The focus, he says, has turned very much to these tests over those that detect antibodies, which were once branded a “game-changer”.

Those have now been put “on the back-burner”. “We still don’t really know what antibodies do to protect you,” Sir John says.

Lateral flow tests, on the other hand, could allow for people to start doing things such as returning to cinemas, travelling by aeroplane again and attending football matches.

“It would definitely put us in a good holding pattern until we do get a vaccine,” Sir John says.

It seems maybe he is not in the LFT loop and doesn't know how good the Avacat test is?

There were actually two relevant articles in the Telegraph today. The discussion on the earlier thread this morning is only about one, an article about Moonshot testing. So far as I can see the first few paragraphs, which purport to describe the current government position, was unfortunately not posted? Though perhaps not revealing anything new, the way these paragraphs are put together is interesting - the use of the phrase 'proving grounds' etc:

"A pilot of the Moonshot Covid-19 testing programme will begin next month despite Government scientific advisers warning that it could be seen as "authoritarian".

Salford and Southampton have been chosen as the proving grounds for mass testing, with separate pilots to be carried out at sports and leisure venues such as football stadiums and theatres.

Although the test kits on which Boris Johnson has pinned his hopes are still in development, ministers want to get over the logistical hurdles so they are ready once the technology exists."

To my mind this latter clearly relates to the 10 million a day 'pregnancy' style tests that Boris wants, with the 'proving grounds for mass testing' and 'separate pilots to be carried out at sports and leisure venues' confirming that the Salford / Southampton work is aimed at the logistics, exploring how rapid 'pregnancy' style testing can best be used, rather than to validate the tests themselves. The rest of the article is a bit muddled, reporting a reluctance on the part of the Sage and some of its scientific advisors to go along with mass testing and describing in detail the iAbra and Halo tests, inferring they are the ones that will deliver the 10 million tests a day.

The second article reports how ministers think the new tracing app can operate as a 'passport' and says this about how it might relate to the proposed Moonshot mass testing:

"The Telegraph understands that ministers are looking at integrating the app into the ambitious Moonshot project to accelerate UK testing from around 200,000 a day to 10 million by 2021, radically increasing the ease with which people can get one.

A senior Government source said: "The app will launch on September 24, while the Moonshot pilot doesn't start until October and we don't yet know when that might become a nationwide programme.

"In time, though, the Moonshot could well be integrated with the app so that you can use the app to show that you have tested negative. It's early days for the Moonshot, though, so we will have to work out what is possible."

Hopefully ministers are now too committed to all this for them to back track. The question is how quickly they can get it all to come together. And hopefully the anticipated high performance of the AVCT test will win over Sage - the comments of Lord Bethell in the recent House of Lords were very complimentary, referring to what I believe can only be the Avacta test - well worth watching right through.

And at the very end, the relevant bit ! is:

With a large and well-resourced partner, a neutralising Affimer therapy could potentially be developed more quickly than a vaccine and we believe that the likelihood of success would be high.

Its from

RNS 15 May 2020, SARS-COV-2 Neutralising Affimers - Potential for a COVID-19 Therapy

Avacta Group plc (AIM: AVCT), the developer of Affimer(R) biotherapeutics and reagents, is pleased to announce that several of the Affimer reagents recently generated for development of a point-of-care COVID-19 antigen saliva test have now also been shown to block the interaction between the virus' spike protein and ACE2, a receptor on human cells that is key to the virus infection pathway(1) .
Avacta has already successfully generated a large number of Affimer reagents that bind to the SARS-COV-2 virus' spike protein as part of its partnership with Cytiva (formerly GE Healthcare Life Sciences and now part of Danaher Corp). As previously announced, Avacta and Cytiva are working together to develop a rapid point-of-care COVID-19 antigen saliva test to be mass produced for large-scale population screening and for self-testing by consumers.
Further work at Avacta(2) has now shown that several of these Affimer reagents block the interaction between the virus' spike protein and a receptor found on human cells, called ACE2, to which the virus spike protein binds in order to infect cells. Affimer reagents that block the binding of the virus spike protein to ACE2 therefore have the potential to prevent infection and act as "neutralising" therapies.
Neutralising therapies could be given to those exposed to the virus (such as health and social-care workers) to prevent infection, as well as to patients already infected by the virus, to help treat and prevent disease progression.
Large pharmaceutical companies, such as AstraZeneca and GSK, are now starting programmes to develop neutralising antibodies in an attempt to block the SARS-COV-2 spike protein's interaction with ACE2. Avacta has now demonstrated that several Affimer reagents also perform this blocking function and the Company is now seeking a partner that has the resources available to develop a neutralising Affimer therapy as quickly as possible.

Dr Alastair Smith, Chief Executive Officer of Avacta Group, commented:
"This is a very exciting development in the COVID-19 programme. It only took four weeks to generate more than fifty Affimer reagents that bind the SARS-COV-2 virus spike protein and amongst those we now know that there are neutralising Affimers that block the interaction with a key human cell surface receptor, raising the potential for a therapy to prevent infection.
Recently GSK invested $250 million in Vir Biotechnology Inc(3) to develop potential antibody treatments for COVID-19 by selecting antibodies from recovered patients, and AstraZeneca also recently announced that it would start a programme to find new monoclonal antibodies that block the spike/ACE2 interaction(4) .
There is significant potential for a therapy that could help prevent infection and limit the progression of the disease, providing immediate benefit to patients. With a large and well-resourced partner, a