COVID-19 — Coronavirus

Status
Not open for further replies.
03 March 2002 said:
Doesn't is not correct but for all intents and purposes that's true yes. You description here is probably quite spot on for the average person to understand what's happening here.

Also, scientists will rarely ever say this happens at this time. What's more correct is that it has only been tested up to the 5th day and such we can only say it's stable for 5 days.
Click to expand...
I got there eventually :)
 
domalino said:
I'm quite interested in this.

Are you saying they've likely not had time to work out what temperature it has to be stored at yet and -70C is just the default position they take until they've worked out how long it takes to degrade at -20 or 2-8?

I would have thought that would be something they'd do straight away because of its ramifications for the logistics of widespread rollout.
Click to expand...
You are correct.

The thing is manufactured to the scale of the planned clinical trials with the knowledge that by no means do all drugs entering clinical trials make it to market. Some even get shelved for other reasons, despite promising clinical trials. It sounds like not a lot of work to do those tests but it really is. They take time, if you want to demonstrate stability for 6 months, well guess what? it's on stability for 6 months, plus the time it takes to do the tests, often a week or 2, then a few more weeks to review data / produce reports and have QA work done. Stability studies usually comprise a large chunk of development.
There are rules and regulations to follow and usually you'd lay down several 100s/1000s of vials which eats into your development costs as these are no longer available for clinical trials.

There are some more novel therapeutics beginning to enter the market called Oligonucleotides which can cost in excess of $1M/gramme to manufacture and so you can imagine things like stability are the last thought once you know it's stable at -80c.

When you start to consider all these things you see why it costs ~15B to bring them to market.
 
Healdplace said:
Patients 873 v 1117 v 1257 v 1235 today - Patients DOWN - but then if you lose 103 to death in 48 hours numbers will go down.
Click to expand...

Healdplace said:
ICU ventilators 72 v 85 v 94 v 93 today - decrease - but the same caveat of so many deaths will reduce these numbers.
Click to expand...
Whilst you would think this was right, the graphs here have a new admissions button for hospital admissions and icu admissions,and are both decreasing
www.travellingtabby.com

Scotland Coronavirus Tracker

Current and historical data of the Coronavirus outbreak in Scotland. Includes breakdowns by region, maps, charts, and more!
www.travellingtabby.com www.travellingtabby.com
 
domalino said:
By this are you saying that they would need it to be at -70C for long term storage but that it's possible it is delivered out to inoculation centres from a regional hub and kept at -20C for a few hours while the vaccine doses are being administered?
Click to expand...
Without committing to those number, the premise is what I'm saying. All focus will now switch to how to make it more stable/easier to transport/easier to administer etc. These are the areas the development costs are clawed back in. If we can make it for half as much and transport twice as much without affecting the cost, it's payday.

Look, we have hexagon but let's make a circle.

I do however still believe that the AZ/Oxford candidate is more of a decagon :)
 
domalino said:
By this are you saying that they would need it to be at -70C for long term storage but that it's possible it is delivered out to inoculation centres from a regional hub and kept at -20C for a few hours while the vaccine doses are being administered?
Click to expand...

The typical way this is done is to define a long term storage condition and period and test the product at start and end.

Also an "in use" period is defined - where the patient/pharmacist has the treatment. That might be, for instance with a bottle of pills designed to last a week, to demonstrate the contents are stable after the seal has been broken for a week. In this case it could be 5 days at fridge temperature.

Finally, transport studies are done, which demonstrate stability for limited periods of time outside of normal conditions eg high temperature excursions if sat on an airport in the sunshine in Texas for that bottle of pills, or perhaps a few hours at room temperature in this case. These can include freeze/thaw cycles as that can affect product performance more than temperature change per se.

Stability may need to be demonstrated with all of these concurrently ie period of shelf life at long term storage PLUS a transport excursion PLUS a period in use - as that's what will happen.

Exactly what studies are done depends on what is already known about the fundamental stability, the intended supply chain and end use. Typically, regulatory agencies will insist on new stability data for each site of manufacture, as subtle changes in manufacture can affect stability.

Now some speculation: This vaccine has not had very long in development at all, so stability data and understanding will be much more limited than usual. There may be almost none for some manufacturing sites. Also, it might be very difficult to characterise degradation for a long RNA strand - I doubt it is possible to precisely characterise, and I've no idea what criteria might be used. It might be that -80 is used because of the difficulty of defining how much degradation is acceptable, or to standardise between sites of manufacture.
 
@Healdplace since you seem to be able to get stats so efficiently, any way we can compare attrition rates year-on-year to see exactly what the difference is in terms of real deaths? I appreciate it'll not be that simple given fluctuations etc but are we actually seeing more deaths from this than the natural death rate?
 
03 March 2002 said:
@Healdplace since you seem to be able to get stats so efficiently, any way we can compare attrition rates year-on-year to see exactly what the difference is in terms of real deaths? I appreciate it'll not be that simple given fluctuations etc but are we actually seeing more deaths from this than the natural death rate?
Click to expand...

I am in no way a maths whizz or expert. So I would have no clue how to do that.

As I have said before I just have the time and the inclination to read the numbers from the governments own site. Anyone can do it if they have the time and patience.

But happy to look for and find any information you need if I can.

That goes for anyone on here wanting something specific.
 
roubaixtuesday said:
Finally, transport studies are done, which demonstrate stability for limited periods of time outside of normal conditions eg high temperature excursions if sat on an airport in the sunshine in Texas for that bottle of pills, or perhaps a few hours at room temperature in this case. These can include freeze/thaw cycles as that can affect product performance more than temperature change per se.

Now some speculation: This vaccine has not had very long in development at all, so stability data and understanding will be much more limited than usual. There may be almost none for some manufacturing sites. Also, it might be very difficult to characterise degradation for a long RNA strand - I doubt it is possible to precisely characterise, and I've no idea what criteria might be used. It might be that -80 is used because of the difficulty of defining how much degradation is acceptable, or to standardise between sites of manufacture.
Click to expand...
I've never heard of a transport study before? Perhaps something for the very end of the drug life cycle, post-launch?

I'm not sure what the application would be in the case of temperature deviations. That would not comply with GMP requirements and would likely lead to the loss of that material or writing a technical memo to assess the impact of the temperature fluctuation. Certainly that material would not enter patients.

I'm by no means an expert in RNA/DNA but I'd have thought the RNA/DNA would be incredibly stable, the loss of the lipid capsule 'vehicle' into the cell would be far more damaging and indicative of degradation. Those tests are fairly easy to do using UV spectroscopy.
 
shemnel said:
there are indications in other sources that the current deaths from ALL respiratory causes (inc. Covid-19) is currently stable and that excess deaths in the UK from all causes is still within 1 s.d., for the time of year. That was up to end of Oct i think, so things can change.
Click to expand...

Data here. Excess deaths are rising in line with COVID deaths

Coronavirus (COVID-19) latest insights - Office for National Statistics

The latest data and trends about the coronavirus (COVID-18) pandemic from the Office for National Statistics and other sources.
www.ons.gov.uk
 
roubaixtuesday said:
Data here. Excess deaths are rising in line with COVID deaths

Coronavirus (COVID-19) latest insights - Office for National Statistics

The latest data and trends about the coronavirus (COVID-18) pandemic from the Office for National Statistics and other sources.
www.ons.gov.uk
Click to expand...
Cheers @roubaixtuesday. Interesting stuff, another morbid rhetorical question would be, given the average age of COVID/COVID-related death, what impact will this have on the average age of people worldwide?
 
03 March 2002 said:
I've never heard of a transport study before? Perhaps something for the very end of the drug life cycle, post-launch?

I'm not sure what the application would be in the case of temperature deviations. That would not comply with GMP requirements and would likely lead to the loss of that material or writing a technical memo to assess the impact of the temperature fluctuation. Certainly that material would not enter patients.

I'm by no means an expert in RNA/DNA but I'd have thought the RNA/DNA would be incredibly stable, the loss of the lipid capsule 'vehicle' into the cell would be far more damaging and indicative of degradation. Those tests are fairly easy to do using UV spectroscopy.
Click to expand...

Transport studies are not normally submitted to agencies but done to generate data for internal company use to justify release of material in case of temperature excursions (temperature excursions during transport are a fairly common occurence). Routinely done as part of development now, though less so historically.

Not sure what you mean by loss "into the cell". You think the lipid vehicle is limiting for stability? I can believe that, but I'm very surprised ultra low temperature required for that purpose - I'd assumed something "special" about the RNA strand used - I think these are chemically modified rather than natural RNA? - or maybe the secondary structure matters??

But as you can tell, this is pure speculation rather than informed comment
 
Healdplace said:
That Dr Yeadon sells his argument well and I can see why he thinks as he does.

And goodness me if he is right the world can celebrate making itself bankrupt for nothing.

But that's the question. One country not seeing this, I can get. Many countries missing these facts I can get too if driven by ideology, just about. But every country sheepishly believing the opposite is hard to get your head around.

They must all be guided by scientists who broadly think the opposite. Why not one or two with the opposing view having had influence? And based on experience of things like the 3 waves of the 1918/1919 killer flu we SEEM to have obvious evidence that even when a virus runs unchecked as we had no real way to fight it then it can return seasonally in waves and be worse, which he seems to be denying then I can understand the reservations too.

I suspect the answer is somewhere in the middle and both sides here are right to a degree. That way more have had it/are immune than realised - that as a result it likely is generally waning outside localised spikes - not getting worse widely - but that it may not yet be all but literally over as he seems to think.

Much as I would dearly love him to be right.
Click to expand...
Isn’t it possibly, that the down side is always unforgiving? If the ‘scientists’ and the government said it’s probably over and we will just see the same seasonal respiratory deaths we always see, and then it wasn’t, big trouble I suspect.
If they say 4000 deaths a day, R number at 2, hospitals overflowing and ‘cases’ rising everywhere, if they’re wrong, it doesn’t really matter. Even if we end up at 1000 deaths a day, they’ve ‘saved’ 3000 a day....
It actually looks like the R was 0.9 on November 6th. Therefore, admissions, patients in hospital and deaths will all be coming down on December 2nd (probably by 24th November if not before). Will the lockdown have had anything to do with it? Probably not. Will they say it did? I’d imagine so...
 
Status
Not open for further replies.
Unread Posts

Don't have an account? Register now and see fewer ads!

SIGN UP
Back
Top