Several countries in the European Union (EU) have temporarily suspended use of AstraZeneca’s COVID-19 vaccine due to a small number of incidences of blood clots forming in people who had received the COVID-19 vaccine while the European Medicines Agency and other regulatory agencies evaluate and report findings from their investigations.

Regulators in Germany, France, Spain, Ireland, Luxembourg, and Latvia announced this week (week of March 14, 2021) that they have suspended distribution of AstraZeneca’s COVID vaccine due to small number of reports of thromboembolic (blood clotting) events, until the assessment of the vaccine by the EMA’s Pharmacovigilance Risk Assessment Committee (PRAC) is completed.

Earlier this month (March 2021), regulators in Denmark, Norway, and Austria announced that they had suspended the vaccine distribution for at least two weeks for the next 14 days (as reported on March 11, 2021) while European regulatory authorities conduct an investigation.

The World Health Organization (WHO) is in contact with the EMA and global regulators for the latest information on COVID-19 vaccine safety. The WHO Global Advisory Committee on Vaccine Safety is assessing the latest available safety data for the AstraZeneca vaccine. Once that review is completed, WHO says it will communicate the findings to the public.

The EMA is working with AstraZeneca, experts in blood disorders, and other health authorities, including the UK’s Medicines and Healthcare products Regulatory Agency (MHRA).

This week (March 18, 2021), the MHRA and the EMA reaffirmed that the benefits of AstraZeneca’s COVID-19 vaccine continue to outweigh the risks.

The MHRA reported its review of the small number of thromboembolic events in over 11 million people who received the vaccine in the UK. The UK regulator confirmed that the benefits of the vaccine in preventing COVID-19 far outweigh the risks, and people should continue to get vaccinated when asked to do so. The MHRA concluded there is no evidence that blood clots in veins are occurring more than would be expected in the absence of vaccination. A detailed review of five UK reports of a very rare and specific type of blood clot in the cerebral veins (sinus vein thrombosis) occurring together with lowered platelets (thrombocytopenia) is ongoing. This has been reported in fewer than one in a million people vaccinated so far in the UK and can also occur naturally; a causal association with the vaccine has not been established.

Subsequently, the EMA’s PRAC concluded there was no increase in the overall risk of blood clots (thromboembolic events) with the vaccine. However, the PRAC also concluded that, for very rare cases of serious thromboembolic events, a causal link with the vaccine is not proven, but is possible and deserves further analysis. Furthermore, there was no evidence of a problem related to specific batches of the vaccine or to particular manufacturing sites.

AstraZeneca says it will continue to work closely with health authorities to ensure the appropriate use of the vaccine. The company says it will implement the recommendations of the PRAC, including the update of the product information, while continuing to understand the nature and relevance of these events to ensure the safe delivery of the vaccine.

Supply to the EU

AstraZeneca also reported that it is facing shortfalls from its European supply chain due to lower-than-expected output from the production process. The company reported that it was looking to compensate for part of this shortfall by sourcing vaccines from its international supply network. In a March 12, 2021 statement, the company said it is disappointed to announce a shortfall in planned COVID-19 vaccine shipments to the EU despite working to accelerate supply.

Half of the EU’s supply in the second quarter of 2021 and 10 million doses in the first quarter of 2021 were due to be sourced from the company’s international supply chain. The company said export restrictions will reduce deliveries in the first quarter of 2021 and are likely to affect deliveries in the second quarter of 2021.

AstraZeneca started delivery of the vaccine to the EU in February (February 2021), and aims to deliver 100 million doses in the first half of 2021, of which 30 million are due to be delivered in the first quarter of 2021. The company is collaborating with the European Commission and EU member states to address the supply challenges.

Manufacturing in Japan

In a separate development, Daiichi Sankyo has started manufacturing the AstraZeneca’s COVID-19 vaccine in Japan. The marketing approval application for AZD1222 in Japan was submitted by AstraZeneca on February 5, 2021.

Daiichi Sankyo is using undiluted solutions provided by AstraZeneca to manufacture the vaccine in Japan, including the vial filling and packaging, in accordance with the companies’ outsourcing agreement, which was concluded with AstraZeneca in February 2021. The manufacture of the vaccine is being undertaken by Daiichi Sankyo Biotech Company, a subsidiary of Daiichi Sankyo.

Source: AstraZeneca (March 18, 2021 safety update), AstraZeneca (March 14, 2021 safety update), AstraZeneca (supply update), World Health Organization, European Medicines Agency (investigation), European Medicines Agency (update), Germany, France, Spain, Ireland, Luxembourg, Latvia, and Daiichi Sankyo