How the Pfizer COVID vaccine gets from the freezer into your arm



from www.shutterstock.com

Nicholas Wood, University of Sydney

From Monday, people at high risk of COVID-19 will be lining up to receive the Pfizer vaccine, marking the start of Australia’s long-awaited COVID vaccination program.

We’ve heard about the need to store the vaccine frozen at about -70℃ — a temperature well below freezing and unusually cold, even for Antarctica. The vaccine also comes in a multi-dose vial, meaning the vaccine will have to be diluted then individual doses taken from the vial.

These two aspects make the Pfizer vaccine rollout one of the most complex vaccine programs ever delivered. So all nurses and doctors set to give the Pfizer vaccine in Australia need to have gone through special training in how to store, handle and administer the vaccine.

If you’re one of the high-risk groups set to receive the Pfizer vaccine from next week — because of your occupation or you are in aged- or disability care — here’s what goes on behind the scenes to get the vaccine from the freezer into your arm.


The Conversation, CC BY-ND

Once the vaccine leaves the freezer, the clock starts ticking

Once the vaccine is removed from the “deep freezer” there is no turning back; we don’t want to waste any of these precious vaccine doses.

As you would expect, the vaccine needs to be thawed before it can be injected. Once this happens, it cannot be re-frozen; it must be used.




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The thawing process has rules. Frozen vials are transferred from the freezer to a fridge set at 2-8℃ to thaw. A pack of 195 vials, containing about 975 doses, may take three hours. But it can sit in the fridge for up to five days, if needed. To speed things up, it is possible to thaw the frozen vials for 30 minutes at temperatures up to 30℃. But then, the vaccine needs to be used within two hours.

Either way, people must be lined up ready to be vaccinated to avoid wastage.

Once thawed, the vaccine needs to be mixed gently. So the vaccinator needs to turn each vial up and down (invert it) ten times. They cannot shake the vial as the vaccine is fragile.

Then each vial is split into individual doses

One of the challenges with the Pfizer vaccine is that it comes in multi-dose vials, containing enough vaccine for five or six doses.

Nearly all current vaccines in our national immunisation program are single-use. Many come already prepackaged in the needle and syringe. So for many vaccinators,
“drawing up” and giving a vaccine from a multi-dose vial will be new. This too has rules.

The vaccinator first needs to clean the top of the vial with an antiseptic swab. This is important to ensure the vials remain free from contamination.

Then the vaccinator injects a set amount of sterile saline into the vial, through the top, to dilute the vaccine. Care must be taken not to introduce contaminants during this part of the process.

Nurse giving vaccine to elderly person
Vaccinators have several steps to go through before giving the Pfizer vaccine.
www.shutterstock.com

The vial then needs to be turned up and down ten times to make sure the saline mixes with the vaccine. Again, the clock is ticking. Once the vaccinator injects the saline into the vial and mixes it, the vaccine must be used within six hours. After that, any unused vaccine must be discarded.

The vaccinator must then take a new needle and syringe, clean the top of the vial again and “draw” up 0.3 millilitres of vaccine from the vial. This is a new volume for our vaccinators to get used to as most vaccines given as part of our current immunisation program are 0.5 millilitres.

Once the 0.3 millilitres is in the syringe, it is ready to be injected into the upper arm.

The vaccinator must use a new needle and syringe to “draw” up the next dose. This is repeated until five or six doses have been removed from the vial.




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Ready, set, go

Next, the injection itself. In most cases, the person will be sitting down and have their upper arm exposed so the vaccinator can see the deltoid muscle. This is the large fleshy part of muscle on the outer edge of your upper arm.

There is usually no need to clean the upper arm unless it is visibly dirty. The needle is then inserted at 90⁰ to the arm and the vaccine injected slowly over a few seconds.




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Not sure about the Pfizer vaccine, now it’s been approved in Australia? You can scratch these 4 concerns straight off your list


That’s not all

Once you have been given the vaccine you will be asked to stay in the clinic for at least 15 minutes to make sure you don’t have any reactions. In some cases, especially if there’s a history of severe allergic reactions, people will be asked to wait for 30 minutes.

Your vaccine details will be added to the Australian Immunisation Register. This is now mandatory. That’s because it is very important we know exactly which vaccine you were given and will be checked when you return for the second dose, 21 days later.




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The Conversation


Nicholas Wood, Associate Professor, Discipline of Childhood and Adolescent Health, University of Sydney

This article is republished from The Conversation under a Creative Commons license. Read the original article.

Not sure about the Pfizer vaccine, now it’s been approved in Australia? You can scratch these 4 concerns straight off your list


Archa Fox, University of Western Australia

The Therapeutic Goods Administration (TGA) has today provisionally approved Australia’s first COVID vaccine, the Pfizer vaccine, paving the way for its rollout to begin in mid-to-late February among high-risk groups.

Two doses will be required, at least three weeks apart. The vaccine can be given to people 16 years and older.

The Pfizer vaccine is based on mRNA technology, a way of giving the body the genetic instructions it needs to make the coronavirus spike protein. The idea is to prime your immune system to mount a protective immune response if you encounter the SARS-CoV-2 virus.

As this is the first mRNA vaccine to be approved for humans, some people have taken to social media to voice their concern. But you can strike these four myths about mRNA vaccines straight off your list.

Myth 1: they enter your DNA and change your genome

Our genome is the complete set of instructions for making all the molecules our cells need to function. Our genome is made of DNA, a different type of molecule to the RNA in the mRNA vaccines. It’s generally not possible for RNA to become part of our genome.

The myth of mRNA vaccines modifying genomes may have surfaced as some types of RNA retroviruses, such as HIV, contain genes that make a protein called “reverse transcriptase”.

A retrovirus is a type of virus that inserts a copy of its RNA genome into the DNA of a host cell it invades, therefore altering the genome of that cell. Taking the example of HIV, reverse transcriptase can convert the HIV RNA into DNA, so the HIV genes can enter our genome.

But SARS-CoV-2 is not a retrovirus and the COVID-19 mRNA vaccines don’t make reverse transcriptase. They only contain one gene: the gene for the SARS-CoV-2 viral spike protein.




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So, the only way the COVID-19 vaccine mRNA might enter your DNA is if you were unlucky enough to be infected at precisely the same time with HIV, or another kind of retrovirus, and this virus was active for the few short hours the vaccine mRNA was present in your cells. The chances of this happening are vanishingly small.

Unlike DNA, mRNA doesn’t last long in our cells. The mRNA lasts just long enough to instruct the cell to make viral spike protein, but will then break down, like all the other thousands of mRNA molecules our cells make all the time.

Myth 2: they connect you to the internet

The Pfizer mRNA vaccine contains a piece of mRNA which is coated in a lipid (fatty) droplet. The lipid helps the vaccine enter our cells, as the membrane holding our cells together is also made mostly of lipid. The vaccine and the membrane can fuse easily, depositing the mRNA inside the cell.

Some other companies, developing different mRNA vaccines, are exploring mixing their vaccines with materials called “hydrogels”. The hydrogels might help disperse the vaccine slowly into our cells.

Bioengineers have used similar hydrogels for many years in different ways. For instance, they’ve used them to help stem cells survive after being put inside our bodies.

The use of hydrogels for these stem cell (and other) implants has created a myth they’re needed for electronic implants, which can be linked to the internet. Conspiracy theorists have jumped from implants to hydrogels to mRNA vaccines based on no evidence.

Since Pfizer’s COVID mRNA vaccines don’t include hydrogels as a component (nor do Moderna’s), this is not a concern. Though this wouldn’t be a valid concern even if these vaccines did use hydrogels.




Read more:
How mRNA vaccines from Pfizer and Moderna work, why they’re a breakthrough and why they need to be kept so cold


Myth 3: they cause autoimmune disease

Autoimmune diseases, such as arthritis and multiple sclerosis, are chronic (long-term) illnesses where our immune systems attack our own cells.

It’s not entirely clear where this belief has come from, but we don’t have any evidence to suggest mRNA vaccines can cause autoimmune diseases.

The fact mRNA is very short-lived inside our cells indicates this is highly unlikely, because you would usually need a long-lived foreign agent to trigger a chronic autoimmune response.

Interestingly, mRNA vaccines are now being designed and delivered to treat autoimmune diseases, such as multiple sclerosis. However, these are still at the early stage of development.

Myth 4: they make you infertile

Recent discussions on Twitter suggested antibodies against the SARS-CoV-2 spike protein might “cross-react” and also target a protein in the placenta. If the immune system attacks the placenta, as the argument goes, that could make women infertile.

The basis for this idea is that coronavirus spike proteins, including that of SARS-CoV-2, have a very short region of similarity to a protein called syncitin-1 found in human placenta.

That amounts to a short stretch of five or six amino acids, where three or four amino acids are identical between coronavirus spike proteins and syncitin-1. Proteins as long as the spike protein will always share tiny regions of similarity with other human proteins. Our immune system is trained to ignore this.

The chances of making antibodies that cross-react with syncitin-1 are very small.

There’s no evidence antibodies against any coronavirus cause infertility. If coronavirus spike proteins did lead the immune system to attack the placenta, we’d see widespread infertility after common cold seasons, which are caused by a range of viruses, including coronaviruses.

It’s true pregnant women were not included in the clinical trials for the Pfizer vaccine. Excluding this group from clinical trials is standard practice, but many have argued more COVID vaccine trials should include pregnant women.




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All technologies were new once

Of all the vaccine technologies being explored against COVID-19, mRNA vaccines have proved the most efficient in reducing the incidence of severe COVID disease.

However, we still don’t fully understand their long-term safety, as with all new medicines.

The TGA’s approval is valid for two years and it will continue to monitor
the vaccine’s safety both in Australia and overseas.The Conversation

Archa Fox, Associate Professor and ARC Future Fellow, University of Western Australia

This article is republished from The Conversation under a Creative Commons license. Read the original article.

The Pfizer vaccine may not be the best choice for frail people, but it’s too early to make firm conclusions


Nathan Bartlett, University of Newcastle

Reports of about 30 deaths among elderly nursing home residents who received the Pfizer vaccine have made international headlines.

With Australia’s Therapeutic Goods Administration (TGA) expected to approve the vaccine imminently and the roll out set to begin next month, this development might seem like cause for concern around the safety of the vaccine.

But there are a few reasons it shouldn’t be.




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What we know

We haven’t seen this issue reported in any other countries which are rolling out the Pfizer vaccine.

Norway has reported about 45,000 people around the country have been vaccinated against COVID-19 so far. Their vaccine program has mostly focused on residents in nursing homes.

In other countries, there may be more of a focus on frontline health-care workers in the first instance. So if there is any association between deaths in the elderly and this vaccine, it may not be apparent as yet.

It also depends on surveillance. Norway may have an especially rapid surveillance and reporting system in place, efficiently tracking everyone who has been vaccinated and quickly reporting any adverse outcomes.

We would expect surveillance reporting from other countries with an active vaccination program soon, increasing data critical to building a more accurate picture of vaccine safety across different populations.

Norway’s reports will sensitise other countries to monitoring vaccine recipients closely, particularly those in nursing homes who are older and vulnerable. We may see further reports on this coming through in coming weeks from other countries.

But we also may not. We have limited information regarding these cases in Norway. The people reported to have died were elderly and very frail. Many had significant underlying health conditions common in the very old, and may have been nearing the end of their lives independent of the vaccine.

Though they are under investigation, it’s important to note the deaths have not been linked conclusively to complications from the vaccine. Meanwhile, Australian experts have called for calm.

Vaccines and the elderly

In the recent history of vaccines, we haven’t seen any trends showing deaths in elderly people following vaccination. For example, there’s no evidence the annual influenza vaccine has been associated with deaths in older people — or people of any age.

It’s important to note though, that in making a comparison with the flu shot or another vaccine and the Pfizer vaccine for COVID-19, we’re comparing apples and oranges.

The Pfizer vaccine is based on mRNA technology, which is completely new in a human vaccine. This technology introduces part of the genetic material of the SARS-CoV-2 virus in the form of messenger RNA (mRNA). This instructs your cells to make part of the virus which stimulates an immune response that inhibits infection and protects against disease.

All vaccines are designed to generate an immune response — albeit in different ways — to prepare our bodies to fight the virus if and when we encounter it.

A nurse administers a vaccine to an elderly lady wearing a mask.
With any vaccine, different people will experience side effects differently.
Shutterstock

Creating an immune response leads to inflammation in the body. Some people will experience no side effects from a vaccine, but the inflammation can manifest in different ways in different people and between different vaccines. This may mean a reaction at the site of the injection, or fatigue, or feeling unwell.

The deaths in Norway were reportedly associated with fever, nausea and diarrhoea, which, while at the severe end of the spectrum of vaccine side effects, would be tolerable for the vast majority of people.

How different people will respond to the mRNA is what we’re starting to understand now. It’s possible this vaccine will have more serious effects in older, vulnerable people where the initial inflammatory response could be overwhelming.

But it’s still too early to draw any conclusions.




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Side effects show a vaccine is generating an immune response

Vaccines need to generate an immune response in order to work, and side effects are a byproduct of our bodies mounting an immune response.

While the deaths are sad, they shouldn’t be cause for alarm. This actually tells us the vaccine is stimulating an immune response. For most people that response will be entirely tolerable and lead to development of immune memory that protects you from severe COVID-19.

The big challenge for any vaccine is generating enough of an immune response so you’re protected from the disease in question, but not too much that you experience serious adverse effects. Where this line in the sand exists will vary across different people, but the oldest and frailest vaccine recipients are likely to be most at risk of severe, potentially life-threatening reactions.

So for those who may be more susceptible, we may want to be a little more cautious. In approving the Pfizer vaccine, the TGA may consider advising against this particular vaccine for people who are very elderly and frail, particularly those who have other conditions and are potentially nearing the end of their lives.

Ideally, the vaccine should be considered on a case-by-case basis for this group, carefully weighing up the risks and benefits in each situation, based on the best available data.




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The Conversation


Nathan Bartlett, Associate Professor, School of Biomedical Sciences and Pharmacy, University of Newcastle

This article is republished from The Conversation under a Creative Commons license. Read the original article.

The Oxford vaccine has unique advantages, as does Pfizer’s. Using both is Australia’s best strategy


Kylie Quinn, RMIT University; Holly Seale, UNSW, and Margie Danchin, Murdoch Children’s Research Institute

On Sunday, federal Chief Medical Officer Professor Paul Kelly said most Australians will be offered a vaccine from Oxford-AstraZeneca.

Australia currently has agreements in place to receive 53.8 million doses of the AstraZeneca shot, and 10 million doses from Pfizer-BioNTech.

So how do these two vaccines compare, how will they be used in Australia, and what can we learn from other vaccines?




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Comparing the two

Both the Pfizer and AstraZeneca vaccines induce immunity but in different ways. They both deliver the instructions for how to make a target on the virus for our immune system to recognise the spike protein.

The Pfizer vaccine packages the instructions up in a droplet of fat, while the AstraZeneca vaccine packages the instructions up in the shell of a virus, the adenovirus.

Clinical trials for both vaccines have shown they’re broadly safe.

In terms of efficacy, the Pfizer vaccine protects 94.5% of people from developing COVID.

The AstraZeneca shot protects 70% of people on average — still pretty good and on par with the protection given by a flu vaccine in a good year.

However, the optimal dose and timing of AstraZeneca’s shots is still unclear. One trial reported 62% efficacy, and another 90%, with a low dose for the first shot and/or longer break between doses possibly improving protection. More studies are underway to define this and the Therapeutic Goods Administration, Australia’s regulatory body, will evaluate new data as it comes through.

In any scenario, the AstraZeneca vaccine will still protect the majority of people that receive the vaccine from disease.




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While the Pfizer vaccine was more protective in clinical trials, the AstraZeneca vaccine has other advantages that could make it more appropriate for use outside of clinical trials:

From a logistical perspective, the AstraZeneca vaccine has a major advantage. The ability to distribute vaccines can be almost as important as the vaccine’s effectiveness.

The effect of these advantages on the impact of this vaccine shouldn’t be underestimated. We have lots of people to vaccinate, a low disease burden currently, are far away from the rest of the world in terms of shipping, and Australia is a pretty big country, so distribution to rural and remote communities is a massive hurdle.

Efficacy isn’t the only thing we should consider

It can be helpful to look at the flu vaccine as a contrast. The flu vaccine is far from perfect — it provides moderate protection, with effectiveness varying between different groups of people and from season to season. For example, in the 2015/16 season in the United States, the quadrivalent influenza vaccine (which covers four strains) was about 54% effective against laboratory-confirmed influenza.

People know it’s not perfect, but people don’t generally judge whether they’ll receive a vaccine based on its effectiveness alone. We know from talking to the community that many factors influence motivation, especially perceived risk and severity of infection, and confidence in the safety of the vaccine.

Every year, access to flu vaccines is prioritised to those at most risk, such as people with medical conditions, Aboriginal and Torres Strait Islanders and those aged 65 years and older. The public has confidence in this approach. We need to protect those most at-risk first, and we don’t have an issue doing this day-to-day. We now have a similar challenge with the new COVID vaccines.

The best approach for protecting everyone’s health amid the pandemic is to provide different vaccines to different people according to need and availability, at least in the short term. The best vaccine is always the one you can get to the communities that need it before they urgently need it.

Australia’s combination strategy

Because Australia is essentially COVID-free at present, it means we’re in a unique situation that permits a “combination” vaccine strategy.

The Pfizer vaccine is perfect for preventing the most extreme outcomes for people at very high risk of infection or disease: people on the frontlines of the fight against COVID and older people or people with high-risk health conditions.

The AstraZeneca vaccine has the ability to protect a large number of people against disease quickly, because we can make it easily and distribute it quickly.

As a result, Pfizer is likely to be prioritised for people with higher risk and AstraZeneca is likely to be prioritised for everyone else.

We won’t all be able to get the Pfizer vaccine straight away, so for many of us the choice in the short term will be between a 70% efficacious vaccine or no vaccine.

We all stand to benefit from a strategy that protects extremely vulnerable groups from severe disease and aims to rapidly generate immunity in the rest of our community.

There may also be other vaccines that become available. Australia is part of COVAX which can distribute a variety of vaccines, and it also has an agreement for a vaccine made by Novavax, pending the outcome of phase 3 clinical trials. There could be other vaccines that emerge or other agreements developed, and Australia’s strategy will no doubt respond to that.




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Nevertheless, both the Pfizer and AstraZeneca vaccines are essential tools in our public health toolkit, with vital roles to play in protecting the entire Australian population. We’ll also need to continue to use other public health tools like testing and contact tracing.

Factoring in effectiveness, availability and distribution challenges, a strategy that uses a combination of the two vaccines for Australia is the best of both worlds.


Shane Huntington co-authored this article. He is Deputy Director, Strategy and Partnerships, Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne.The Conversation

Kylie Quinn, Vice-Chancellor’s Research Fellow, School of Health and Biomedical Sciences, RMIT University; Holly Seale, Associate professor, UNSW, and Margie Danchin, Associate Professor, University of Melbourne, Murdoch Children’s Research Institute

This article is republished from The Conversation under a Creative Commons license. Read the original article.

People with severe allergies warned off Pfizer COVID vaccine for now. But that may change as more details emerge


Giovanni Cancemi Shutterstock

Nicholas Wood, University of Sydney and Ketaki Sharma, University of Sydney

Two people in the United Kingdom have experienced an allergic reaction to the Pfizer/BioNTech COVID-19 vaccine. This led the UK medicines regulator to issue precautionary advice earlier this week that “people with a significant history of allergic reactions” should not be given this vaccine for now.

This is an appropriate cautious move. The advice may change once we understand more about what caused these reactions.

Both people reportedly had known allergies and carried adrenaline autoinjectors, suggesting they had a prior history of severe allergic reactions, such as anaphylaxis, a severe and rapid form of allergy.

At this stage, we do not have many further details about the reported allergic reactions to the vaccine.

An advisory panel to the United States Food and Drug Administration (FDA) has recommended the authorisation of the Pfizer/BioNTech vaccine for emergency use. If the FDA grants this approval, it would be the third country behind the UK and Canada to do so.

How common are these types of reactions?

Severe allergic reactions to vaccines are extremely rare, with anaphylaxis occurring after approximately one per million vaccine doses.

Most reactions reported as possible allergic reactions to vaccines are most likely not true allergies.

Regardless, every person is normally asked about their medical history by their immunisation provider, including whether they have any known allergies, especially to a vaccine or its ingredients, before being vaccinated.




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As almost all severe allergic reactions occur within 15 minutes of exposure to the trigger, it is common around the world to monitor patients for at least 15 minutes after vaccination.

In Australia, it is recommended that any facility where vaccinations are delivered is equipped with the equipment and trained staff to recognise and treat allergic reactions. This applies to all vaccines, including COVID-19 vaccines.

What types of allergens are we talking about?

People can be allergic to a wide range of substances (called allergens), including foods and medications. If someone has a known allergy to a vaccine ingredient, they may be advised not to have that vaccine.

The Pfizer/BioNTech COVID-19 vaccine does not contain any ingredients that commonly cause allergic reactions, and the full list of ingredients has been published by the UK medicines regulator.

It is likely the two people who may have had an allergic reaction after the Pfizer vaccine will be reviewed by an allergy/immunology specialist. If found that they truly had anaphylaxis they would be unlikely to be given the second dose of the vaccine.

However in some situations, people who have had allergic reactions after one dose may be able to receive further doses of the same vaccine using a specialised approach, such as graded dosing, which can avoid triggering a reaction. This approach has not yet been reported for any COVID-19 vaccine.




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Aren’t clinical trials supposed to pick up issues like this?

People with a history of severe allergic reaction to a vaccine or to any ingredient of the Pfizer/BioNTech vaccine were not included in the late phase clinical trial for this vaccine.

This is a precaution designed to protect the safety of the trial participants. Clinical trials usually focus on healthy people without underlying medical conditions, although the Pfizer phase 2/3 trial allowed enrolment of people with stable pre-existing chronic conditions.

Once the safety and effectiveness of a vaccine is well established in healthy people, it can then be offered to other populations, such as people with severe underlying medical conditions.

This trial includes more than 40,000 participants and has shown the vaccine to be safe and well tolerated, with no serious safety concerns. The incidence of allergic-type symptoms after vaccination was slightly higher in the vaccinated group at 0.63% compared with the placebo group at 0.51%, however it is not clear whether this slight difference is due to chance.




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What are the implications for people with significant allergies?

As to the implications of this latest news for people with significant allergies, it’s too early to tell. We still don’t know if these reports were true allergic reactions.

There is also no theoretical reason to suspect allergic reactions would be more common with COVID-19 vaccines than with other vaccines, even those using newer technologies.

As always, people should discuss their medical history with their vaccine provider, including any history of allergy.




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We still need ongoing monitoring

Given COVID-19 vaccines will be delivered to millions of people around the world, it’s inevitable some adverse events will be reported. There is potential for an adverse reaction with any medication or vaccine, and that’s why people are monitored after being given a vaccine. A consideration of the risks and benefits is always important when considering whether to have a vaccine.

More than 1.5 million people have died from COVID-19 so far, and thousands more are dying each day. The benefits of vaccination will far outweigh the risks, particularly for the priority population groups most vulnerable to COVID-19.

Ongoing monitoring of COVID-19 vaccine safety is also crucial and will allow us to detect side effects that may be very rare, or which may be related to an underlying medical condition.

In Australia, we’ll be doing this with a robust vaccine safety surveillance system, which will be used to monitor the safety of any licensed COVID-19 vaccines in near-real time, and which will provide publicly available updates.The Conversation

Nicholas Wood, Associate Professor, Discipline of Childhood and Adolescent Health, University of Sydney and Ketaki Sharma, Clinical Lecturer, Discipline of Childhood and Adolescent Health, University of Sydney

This article is republished from The Conversation under a Creative Commons license. Read the original article.

‘Very convincing evidence’: Pfizer now has the data it needs to apply for COVID vaccine approval



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Kylie Quinn, RMIT University

On Wednesday, Pfizer and BioNTech announced their mRNA vaccine has demonstrated a remarkable 95% efficacy in the “final efficacy analysis” of its phase 3 trial.

The news comes hot on the heels of Pfizer/BioNTech’s interim analysis last week, which pointed to greater than 90% efficacy, and Moderna’s announcement on Monday, also based on an interim analysis, that its vaccine is 94.5% efficacious.

The word “efficacy” describes how well the vaccine offers protection against the target disease during the trial, whereas the word “effectiveness” refers to how well the vaccine protects against the disease in the real world.

This “final efficacy analysis” represents the Pfizer/BioNTech study’s “primary endpoint” — which means there are enough volunteers in the study who have developed COVID-19 to perform a solid evaluation of whether the vaccine is working.

Before the study began, statisticians designing the study identified that 164 people with confirmed COVID-19 would be enough cases to evaluate efficacy (more than 43,000 participants are enrolled in the trial in total).

There were 94 people who had COVID-19 in the interim analysis last week, and they reached 170 people this week — 162 of whom got the placebo and only eight of whom received the vaccine. This is very convincing evidence that this vaccine protects against developing COVID-19 disease.

The fact the primary endpoint was reached so quickly indicates cases are surging in the United States across a lot of the sites where the trial is taking place. Yes, these surging cases are providing more data than anticipated for phase 3 clinical studies; but they also highlight the urgency of the situation in the US.




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Deeper insights

Pfizer/BioNTech have provided three additional important pieces of information.

First, the vaccine appears to be safe. Volunteers in the study were asked to report different symptoms after receiving the vaccine, and the most common symptoms of note were fatigue and headaches (3.8% of participants experienced more severe fatigue, and 2% headaches).

Second, the vaccine appears to protect against severe disease. The trial saw ten people become severely unwell with COVID-19, only one of whom had received the vaccine. This is a huge relief, because severe COVID-19 puts immense pressure on health-care systems.

Third, they’ve reported the vaccine has 94% efficacy in older people. This is crucial as older adults are bearing the brunt of COVID-19. In Australia, people over 65 make up only 20% of cases but almost 50% of all ICU admissions and more than 95% of deaths from COVID-19.

This efficacy in older people exceeds what many researchers had anticipated, as vaccines often don’t work as well in this group.

An elderly lady wearing a mask walks with a frame in a garden.
The Pfizer/BioNTech vaccine appears to work equally well in older people.
Shutterstock

It’s not a competition

The Moderna vaccine has also shown promising results on those first two measures — safety and protecting against severe disease. We await data on its efficacy in older people.

This rapid-fire succession of press releases may feel like Pfizer/BioNTech and Moderna are competing for the “biggest” efficacy, but competition is not the driving factor.

The primary endpoints are pre-defined by both companies and, when the study reaches them, an interim or final analysis can be performed. Data and safety monitoring boards, independent from the companies, perform these analyses.




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From a scientific perspective, it’s plausible these two vaccines would have similar efficacy, because they use very similar mRNA vaccine designs. In fact, it’s reassuring they are similar because, in science, we must be able to repeat our results. This gives us confidence the data are correct and that we’ll see similar results outside the lab.

In any scenario, competition is redundant when you consider the size of the problem. Nearly eight billion people around the world urgently need a vaccine. Pfizer/BioNTech and Moderna have each indicated they can make enough vaccines for around 500 million people next year. That still leaves seven billion people needing a vaccine — more than enough of a market for both companies, and more.

Any way you look at it, the real competition is against the virus.

What’s next?

In the coming days, Pfizer/BioNTech will apply to the US Food and Drug Administration (FDA) for an emergency use approval for their vaccine. Moderna and other vaccine developers likely won’t be far behind once they reach their primary endpoints.

Applications to other regulatory bodies around the world will follow, including the Therapeutic Goods Administration in Australia. A successful emergency use approval with the FDA can accelerate approvals with other bodies.




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This study will continue for two years to collect “secondary endpoints” — more in-depth details on how the vaccine works and its safety longer term. It will aim to answer three important questions:

  • longevity: how long the vaccine protects people for

  • infection: these latest results show that the vaccine prevents people from getting sick and showing symptoms of COVID-19. But we also need to see whether the vaccine protects people from getting infected in the first place

  • transmission: whether the vaccine reduces the likelihood of an infected but vaccinated person passing the virus on to another person.

It’s fairly straightforward to measure whether a vaccine prevents people from developing disease — you wait for people to report symptoms that could be COVID-19 and then perform a COVID test. Longer timelines and more complicated, laborious lab work are needed to learn about longevity, infection and transmission.

So, there are more insights into the virus and vaccines to come. But these studies are an exciting landmark in vaccine development.




Read more:
Why we should prioritise older people when we get a COVID vaccine


The Conversation


Kylie Quinn, Vice-Chancellor’s Research Fellow, School of Health and Biomedical Sciences, RMIT University

This article is republished from The Conversation under a Creative Commons license. Read the original article.

90% efficacy for Pfizer’s COVID-19 mRNA vaccine is striking. But we need to wait for the full data


Harry Al-Wassiti, Monash University; Colin Pouton, Monash University, and Kylie Quinn, RMIT University

German biotech company BioNTech and US pharmaceutical Pfizer announced on Monday promising early results from their phase 3 clinical trial for a vaccine against SARS-CoV-2, the virus that causes COVID-19.

These early results are what is known as an “interim analysis”. It’s an early look at the data before a study is complete, to understand if there is any indication of whether the vaccine might work.

Currently, this trial has enrolled 43,538 volunteers, giving half the volunteers two doses of the vaccine and the other half two doses of a placebo. These volunteers then continued their normal lives, but they were monitored for any symptoms that could be COVID-19, with testing to confirm.

Analysis of 94 volunteers with confirmed COVID-19 suggests the vaccine has an efficacy of over 90%.

This means that if you took ten people who were going to get sick from COVID-19 and vaccinated them, only one out of ten would now get sick.




Read more:
Australia’s just signed up for a shot at 9 COVID-19 vaccines. Here’s what to expect


Can we get excited yet?

There is more data to come. This is a press release and the data have not undergone “peer-review” through scientific publication, although it has been assessed by an independent monitoring board. The study also won’t be complete until 164 volunteers have confirmed COVID-19, and the estimate of efficacy may therefore change. Finally, the volunteers must be monitored for a defined period of time after vaccination for any side effects and this must be completed.

Important questions also remain. It’s unclear how long protection will last, as this study has only been underway for three months. It’s unclear if this vaccine protects against severe disease or if this vaccine will work equally well in everyone. For example, a phase 1 clinical trial with this vaccine showed that immune responses were lower in older people.

But 90% efficacy is striking. To give some context, the US Food and Drug Administration indicated they would licence a SARS-CoV-2 vaccine with 50% efficacy. The flu vaccine often provides around 60% efficacy and the mumps vaccine, which is currently the fastest vaccine ever made at four years, provides around 88% efficacy.

The BioNTech/Pfizer vaccine could outstrip that, after just nine months of development. This level of efficacy means virus transmission could be very effectively controlled.

That has the research community excited. It bodes well for other vaccines currently being tested for SARS-CoV-2 and we could end up with multiple successful vaccines. This would be great because some might work better in certain populations, like older people.

Multiple vaccines could also be manufactured using a broad range of established infrastructure, which would accelerate vaccine distribution.

Producing mRNA on a commercial scale

The BioNTech/Pfizer vaccine is what’s called an mRNA vaccine.

As this article by Associate Professor Archa Fox, an expert on molecular cell biology from the University of Western Australia, explains:

mRNA vaccines are coated molecules of mRNA, similar to DNA, that carry the instructions for making a viral protein.

After injection into muscle, the mRNA is taken up by cells. Ribosomes, the cell’s protein factories, read the mRNA instructions and make the viral protein. These new proteins are exported from cells and the rest of the immunisation process is identical to other vaccines: our immune system mounts a response by recognising the proteins as foreign and developing antibodies against them.

A problem for Australia is that it can’t make mRNA vaccines onshore yet.

The Australian government has an agreement for ten million doses of the BioNTech/Pfizer vaccine. Since this vaccine requires two doses, this agreement is sufficient for five million Australians. It’s unclear how long it will take until any vaccine is widely available, but we may hear more about this in the coming weeks and months.

The vaccine requires storage at a temperature below -60℃. This will certainly be a challenge for shipping to Australia and local distribution, although not impossible. One solution to this problem is to form vaccination centres to roll out the vaccine once it becomes available. In a briefing by Pfizer, the company said it will use ultra-low temperature shipment strategies and the vaccine can then be distributed on “dry-ice”.

Currently, Australia has no capacity to produce mRNA on a commercial scale given the technology’s novelty. But we (the authors) and others have been working to coordinate and build the manufacturing capacity in Australia for future mRNA vaccine and therapeutics. With financial support aimed at private-public mRNA manufacturing collaboration, Australia can equip itself with this vital technological asset.




Read more:
Australia may miss out on several COVID vaccines if it can’t make mRNA ones locally


The Conversation


Harry Al-Wassiti, Bioengineer and Research Fellow, Monash University; Colin Pouton, Professor of Pharmaceutical Biology, Monash University, and Kylie Quinn, Vice-Chancellor’s Research Fellow, School of Health and Biomedical Sciences, RMIT University

This article is republished from The Conversation under a Creative Commons license. Read the original article.

Bottom of the canal: Pfizer’s billion-dollar tax ploy



File 20170803 28984 16qhxo6
The Netherlands is where nearly $1 billion from Australia was sunk into two companies liquidated three years later.
Alex de Haas/flickr, CC BY-NC

Michael West, University of Sydney

Pharmaceutical giant Pfizer has engaged in a series of paper transactions to create a A$936 million loss in Australia. It is, for all intents and purposes, a billion-dollar exercise in tax avoidance.

Pfizer and its auditor KPMG, the “Big Four” global accounting firm, refused to comment on the transactions or to defend them when presented with questions by this columnist. Pfizer was contacted on numerous occasions and refused. Both parties refused to return emails and phone calls.

These are transactions housed within a byzantine corporate structure. We will outline, in brief, the series of transactions with Pfizer associates in the Netherlands which led to this “bottom of the canal” tax scheme, then provide the background to the company’s activities.

The sequence of transactions

2011: Pfizer Australia Investments Pty Ltd issues $728 million in shares to Pfizer companies in the Netherlands, the US and Luxembourg.

Pfizer Australia Investments (PAI) then uses the cash from this share issue to buy two subsidiaries incorporated in the Netherlands. These are called Pfizer Australia Investments B.V. and Pfizer Pacific Cooperatief U.A.

There is no record of these two companies in Pfizer’s global accounts before December 31 2010.

2014: PAI issues more shares and invests another $208 million in the two Dutch companies. This brings the total investment in these companies to $936 million.

By the end of 2014, the Dutch subsidiaries have been liquidated with zero return for PAI. The financial effect of this round-robin transaction is that share capital of $936 million has been created in Pfizer’s Australian entity and losses of $936 million are recorded in Australia.


Michael West/Rachell Li, Sydney Democracy Network

This ring-a-ring-a-rosy has all the hallmarks of a transaction designed to create almost a billion dollars in losses which can be used for tax purposes in Australia. The Australian company has “invested” almost a billion dollars into two overseas companies which were suddenly liquidated – with no value left for shareholders. Nothing is heard of them since.

It brings to mind the infamous Bottom of the Harbour tax schemes of the 1970s and ’80s where the financial engineers – aided by the top end of the accounting community – made investments in companies, stripped those companies of their assets and left nothing for the taxman.

In Pfizer’s case, almost $1 billion of cash was “invested” in two companies in the Netherlands which went belly up within three years. That left the Australian entity – indeed Australian taxpayers – carrying the can for its losses as the freshly created $1 billion in share capital is now sitting pretty for tax-effective distribution to Pfizer overseas.

A company with form

Pfizer has form on such transactions.

Back in 2011, another Pfizer entity, Pfizer Australia Holdings, created new share capital of $733 million after it bought two subsidiaries from Pfizer Inc. The two subsidiaries were acquired for hundreds of millions of dollars.

Pfizer issued shares, rather than paid cash, to buy these assets from themselves. So, new shares were created at a value of $733 million. This enormous price relied on a fancy asset valuation for the intangible assets held by these subsidiaries, notably “product development rights” of $461 million. These were the main assets acquired.

By 2014, share capital of $408 million of this new share capital had been returned in cash, repatriated to Pfizer companies overseas. And the product development rights had already evaporated (amortised) by $161 million.

Share capital created, assets written off, again. This is the Pfizer pattern. Share capital is created and its assets vanish.

On December 1 2014, yet another Pfizer entity here, Pfizer PFE Pty Ltd, acquired the Innovative Products Oncology and Consumer business from Pfizer Australia Holdings for nil consideration. This included the mysterious product development rights. Nil consideration. These are the rights valued three years earlier at $461 million.

Traditionally, when one company acquires a business from another company, one company is the buyer and the other company is the seller. This immutable principle of commerce does not necessarily pertain to Pfizer.

Pfizer Australia Holdings describes the transfer of this Innovative Products business as a “distribution”, a “transaction with owners in their capacity as owners”, according to its statutory financial statements.

In reality it is no such thing. Pfizer PFE is not an owner of Pfizer Australia Holdings. It holds no shares. It is merely a related party with a common ultimate parent in the US, Pfizer Inc.

Behind this narrative of a “distribution to owners” is tax. When you make profits of hundreds of millions of dollars, avoiding the 30% corporate income tax rate is big business.

Then and now

In 2007, Pfizer Australia Holdings was at the helm of Pfizer’s tax consolidated group in Australia and prepared “General Purpose” financial statements, full financial statements and full disclosures.

In 2008, it switched to preparing “Special Purpose” financial statements with far less disclosure, especially about income tax. KPMG’s 2008 audit report gave this special purpose report a clean bill of health even though required disclosures of changes in accounting policies were not made.

From 2009 to 2012, Pfizer Australia Holdings paid franked dividends to shareholders of $576 million; that is more than half-a-billion dollars going overseas. This is the good stuff, though, the above-board stuff, dividends paid out of profits already taxed in Australia.

After 2012, Pfizer ran out of Australian profits to distribute. It had hit the “patents cliff”. The blockbuster drugs Lipitor and Viagra were coming off patent and being challenged by generic competitors. Pfizer’s sales peaked at $2.2 billion in 2012. This used to be the biggest pharmaceutical company in the country.

Yet Pfizer had hit another cliff. The company was running out of Australian profits to distribute as dividends. It needed another way to rake the money offshore. And it came in the guise of return of share capital – better than dividends as there are far lighter tax obligations.

In 2014, a return of capital of $408 million was made offshore. And now, in 2016, Pfizer has made sure, through transactions with associates in the Netherlands, that there is another billion dollars ready to go offshore when the US overlords make the call.

Two things stand out, two takeaways from the “magic pudding” of Pfizer share capital creation and its bottom-of-the-canal tax scheme.

One, PAI’s audited financial statements claim that two Netherlands subsidiaries were incorporated in Australia. We can find no record of this.

Two, in 2014, PAI invested $208 million in the two Netherlands subsidiaries that were liquidated in the same year for no return. What is an observer to make of that?


The ConversationThis column, co-published by The Conversation with michaelwest.com.au, is part of the Democracy Futures series, a joint global initiative between The Conversation and the Sydney Democracy Network. The project aims to stimulate fresh thinking about the many challenges facing democracies in the 21st century.

Michael West, Adjunct Associate Professor, School of Social and Political Sciences, University of Sydney

This article was originally published on The Conversation. Read the original article.