InDepth – Is there any reason behind AstraZeneca vaccine concerns?

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CDE  – Officials in Ireland and a region of Italy have become the latest in Europe to halt AstraZeneca vaccinations following reports of blood clots and the death of a teacher in Italy given the Covid-19 jab.

The Piedmont region announced on Sunday it was suspending AstraZeneca vaccinations out of “extreme caution” until they find out if the vaccination is linked to teacher’s death.

Luigi Genesio Icardi, the northern Italian region’s health commissioner, said the death of the teacher in the town of Biella was Piedmont’s first encounter with a suspected problem with the vaccine.

The announcement came as officials in Ireland also said they were temporarily suspending AstraZeneca vaccinations based on four new reports of “blood clotting events” in Norway.

Ireland later noted a “small number” of blood clots following vaccinations, however the country’s Health Products Regulatory Authority (HPRA) said the reported clots were not of the nature described by officials in Norway.

The British MHRA also issued a statement saying that it is aware of the action in Ireland, the MHRA is closely reviewing reports but given the large number of doses administered, and the frequency at which blood clots can occur naturally, the evidence available does not suggest the vaccine is the cause. It added People should still go and get their COVID-19 vaccine when asked to do so. AtraZeneca Plc on Sunday said it had conducted a review of people vaccinated with its COVID-19 vaccine which has shown no evidence of an increased risk of blood clots.

The review covered more than 17 million people vaccinated in the European Union and United Kingdom.

“A careful review of all available safety data of more than 17 million people vaccinated in the European Union and UK with COVID-19 Vaccine AstraZeneca has shown no evidence of an increased risk of pulmonary embolism, deep vein thrombosis or thrombocytopenia, in any defined age group, gender, batch or in any particular country,” the statement said.

The company said that safety data of people vaccinated in EU, UK  shown no evidence of increased risk of pulmonary embolism, deep vein thrombosis or thrombocytopenia, in any defined age group, gender, batch or in any particular country.

Reported events of pulmonary embolism reported among those given vaccine is much lower than would be expected to occur naturally in general population of this size.

The company said that it is keeping this issue under close review but available evidence does not confirm that vaccine is cause

During the production of vaccine more than 60 quality tests are conducted by company, its partners & by more than 20 independent testing laboratories. Additional testing is being conducted by co independently by european health authorities and none of re-tests shown cause for concern

In terms of quality, there are also no confirmed issues related to any batch of our vaccine used across europe, or rest of world, adding that “we are going beyond standard practices for safety monitoring of licensed medicines in reporting vaccine events, to ensure public safety” furthermore, in clinical trials, even though number of thrombotic events was small, these were lower in vaccinated group. It also stated that there has also been no evidence of increased bleeding in over 60,000 participants enrolled.

The week that was

Bulgaria, Denmark and Iceland had joined Norway in suspending the vaccine’s use on Thursday while research is conducted into possible health problems.

The batch — ABV5300 — was delivered to 17 European countries (Austria, Bulgaria, Cyprus, Denmark, Estonia, France, Greece, Iceland, Ireland, Latvia, Lithuania, Luxembourg, Malta, the Netherlands, Poland, Spain and Sweden) and in total comprises one million doses.

The halt is expected to further delay Europe’s sluggish vaccine rollout, while critics say it may reduce the public’s trust in the AstraZeneca vaccine.

EU Industry commissioner on Sunday said “The good news is that even though there are delays with AstraZeneca we won’t be late with our vaccination program in the first quarter, as there’s also the very good news from Pfizer, I’m going to say it as there’s no reason not to talk about when things are going well — Pfizer is producing more, much more than planned and is going to deliver more to us, and that may be able to make up for it.”

Malta reported there were no adverse effects reported in Malta from a batch of the AstraZeneca Covid-19 vaccine which is currently being investigated in several countries about a possible link to blood clots. In a statement, the Maltese Ministry of Health said that the Malta consignment of the ABV5300 batch was used up several weeks ago and no doses remain. The health authorities have not received any reports of reactions by the persons who received it.

On Friday, Italy’s medicines agency Aifa stopped using a batch of AstraZeneca doses after a soldier died in Sicily. A link between vaccination and death has not yet been established.

On a national level, however, Italy’s government is sticking with the AstraZeneca vaccine, and Health Minister Robert Speranza stressed in a Sunday interview with La Repubblica newspaper that all vaccines in Italy and Europe are “effective and safe.”

The ministry said that while the health authorities would continue to closely follow the situation, there was no cause for alarm for anyone who had received the jab.

The UK medicines regulator is encouraging people to continue to get their COVID vaccines despite reports from other European countries about halting the vaccination campaign. “Reports of blood clots received so far are not greater than the number that would have occurred naturally in the vaccinated population,” said Dr Phil Bryan, the UK Medicines and Healthcare products Regulatory Agency’s vaccines safety lead.

Euronews reports that the vaccine has several advantages: it is considerably cheaper and easier to handle than the Pfizer and Moderna vaccines and has been given a green light by several regulators including the UK, EU and World Health Organization. Regulators have said the vaccine causes only mild to moderate side effects and is safe and effective at preventing COVID-19. The jab is based on a genetically-altered common cold virus from chimpanzees.

It also focuses on the supply row there was between the EU and AstraZeneca. In fact AstraZeneca had previously made headlines over production delays in the EU, an announcement that further slowed the bloc’s vaccination rollout. This was further confirmed this week, when cuts in delivery were announced.

The EU to release a redacted version of the vaccine contract which stated that AstraZeneca should use its “best reasonable efforts” to manufacture initial European doses.

On Friday, the British drugmaker said it aimed to deliver 100 million doses of the vaccine to the EU in the first half of the year, out of which it is targeting 30 million in the first quarter. “Half of the EU’s supply in the second quarter, and 10 million doses in the first quarter were due to be sourced from the company’s international supply chain,” AstraZeneca said. “Unfortunately, export restrictions will reduce deliveries in the first quarter, and are likely to affect deliveries in the second quarter.” AstraZeneca’s new aim to supply 30 million doses of its COVID-19 vaccine to the European Union by the end of March hinges on the bloc’s drug regulator approving supplies from a factory in the Netherlands, an internal document showed.

Earlier AstraZeneca was criticised about the vaccine’s efficacy, despite performing well in Phase III trials in November. The company’s first press release about the vaccine’s efficacy said it was 90% effective if administered at a half dose and then at a full dose and 62% effective at preventing COVID-19 if administered in two full doses. Mene Pangalos, head of biopharmaceuticals research and development at AstraZeneca revealed to Reuters and the NY Times that a “mistake” had resulted in a lower dose of the vaccine being more effective but experts had criticised the use of an average between the two dosing regimens to determine the efficacy of the vaccine.

On Friday, the EMA said that severe allergies should be added to the possible side effects of AstraZeneca’s coronavirus vaccine after likely links were found to a number of cases in Britain.

The EMA said it had “recommended an update to the product information to include anaphylaxis and hypersensitivity (allergic reactions) as side effects”. The update is based on a review of 41 reports of possible anaphylaxis seen among around 5 million vaccinations in the United Kingdom,” it said in the highlights of the EMA committee that assesses the risk of medications. After careful review of the data, (the committee) considered that a link to the vaccine was likely in at least some of these cases.” The EMA said however that anaphylaxis, or what it called “severe allergic reactions”, was already what it called a “known side effect that may occur, very rarely, with vaccines”.

The AstraZeneca vaccine‘s product information already said that people should be kept under “close observation for at least 15 minutes” after getting the jab in case of allergic reactions.

Originally the list of side-effects included:

  • Tenderness, pain, warmth, redness, itching, swelling or bruising where the injection is given
  • Generally feeling unwell
  • Feeling tired (fatigue)
  • Chills or feeling feverish
  • Headache
  • Feeling sick (nausea)
  • Joint pain or muscle ache

Globally, vaccines are manufactured across drug firms’ existing networks and often need to pass through several countries – and even between continents – before they are ready to inject into arms. Within the EU alone, more than 30 plants from Sweden to Spain are involved in the production of COVID-19 vaccines. AstraZeneca says it has manufacturing capacity in 25 sites across 15 countries, in a chain of partnerships that one company executive likens to a Rubik’s Cube puzzle.

It’s a similar picture for others, including vaccines made by Russia and China, and hitches are common when trying to accelerate production across multiple sites and borders. Switzerland-based Lonza Group AG makes the ingredients for Moderna’s vaccine which then go to Spain to be put into vials. J&J’s shot is made in the Netherlands and sent to the United States for bottling. Pfizer-BioNTech has contracted factories across a network of 13 sites to meet production needs this year – their supplies to Europe also briefly fell short when a plant had to be re-engineered.

But friction between AstraZeneca and the EU in Brussels has continued to chafe since a supplier to the drugmaker in Seneffe, Belgium ran into difficulty in January.

AstraZeneca’s vaccine production starts with living cells being infected with a modified form of the virus. The cells are grown in tanks, or bioreactors, harvested and purified over about two months. Once the active ingredient is created, water and proteins are added and the liquid is bottled – a stage known as ‘fill and finish.’ Sometimes, different stages happen at different sites.

Problems at the Belgian plant, combined with AstraZeneca’s contractual commitments to supply the United Kingdom, meant that even though the product involved was made a short drive from Brussels, EU citizens were left wanting.

The German company IDT Biologika now plans to cover all stages of the cycle. Other German vaccine developers BioNTech SE and CureVac NV, which are at the forefront of new vaccine technology and have both received government funding, will also be part of Germany’s cluster. BioNTech recently brought a new German plant online to produce up to 750 million doses per year and pharma giant Bayer AG will help make CureVac’s shot.

The developers of the Russian vaccine, Sputnik V, have also made inquiries about producing it in the region, Saxony-Anhalt premier Haseloff said. Russia’s sovereign wealth fund Russia’s Direct Investment Fund (RDIF), which is promoting Sputnik V internationally, declined to comment.

AstraZeneca’s arrangement with IDT is similar to other deals the company has reached, for instance in Japan and Australia. Arrangements like this also help reduce the risk for companies.

AstraZeneca declined to comment on the deals it has reached, but one of its executives has said in the past the company tried hard to create independent supply chains to enable full access to the vaccine around the world.

Building up vaccine production capacity makes sense given the need to vaccinate the world, potentially repeatedly, against COVID-19, as well as the threat of future pandemics.

But large manufacturing sites are the most efficient and at some point, extra capacity spread across many countries may not be economical.

Based on a review of reports on dpa/reuters/politico/euronews/ansa