AstraZeneca and one of its key European suppliers have defended the quality of their Covid-19 vaccine production process after the EU drugs regulator said it was investigating whether there could have been manufacturing defects in specific batches.
The European Medicines Agency inquiry follows reports of possible side-effects, including blood clots, that have led to at least 16 European countries to suspend or limit use of the shot. The EMA has said it was unlikely the reported adverse events were connected to the vaccine or to specific batches but that a link could not yet be ruled out.
AstraZeneca said each batch of vaccine is subject to “more than 40 different quality control tests” between the laboratory and people’s arms.
“Every batch made in our supply network must meet the same exacting production and quality standards. Regular quality control testing is carried out at every stage of production, to ensure the production process is well controlled and results are consistently within required levels,” the company said in response to questions. “Each of these tests have been validated and has a specific step-by-step process that must be carried out.”
In Europe, where most of the reported blood clot events have been recorded, Oxford/AstraZeneca’s vaccine is manufactured in a multi-step process. The active ingredient or drug substance is supposed to be produced at plants including one in Belgium and one in the Netherlands. It is then shipped to so-called “fill and finish” facilities where the drug product is manufactured and put into vials.
One of AstraZencea’s fill and finish facilities is the Anagni plant in Italy, run by US company Catalent. That plant produced two of the batches that initially triggered the suspension of vaccinations in Austria and Italy, ABV 5300 and ABV 2856.
Those batches are not being used in the UK, according to UK health officials, but they have been distributed widely across Europe.
Mario Gargiulo, the president of the European biologics division of Catalent, told the Financial Times that every batch shipped from Anagni had met rigorous quality specifications and testing.
“All documentation and quality assessments pertaining to these batches were once again reviewed by Catalent, AstraZeneca, and the Italian [drugs] regulator, AIFA,” he said. Italian regulators will inspect the plant a third time this week, officials said.
Anagni had a manufacturing problem earlier this year, before delivery of the Oxford/AstraZeneca vaccine to the EU had begun, according to people familiar with the matter. On that occasion, RIVM, the Dutch regulator in charge of batch testing of Oxford/AstraZeneca doses for the bloc, found that one batch was less potent than required because of a malfunction at the end of the drug product manufacturing process and the batch was not released, the people said.
In response to questions about that manufacturing issue, Gargiulo said: “Every Catalent product that has been made available to the public has been fully reviewed, quality-checked, and approved by Catalent, our customer, and the appropriate regulatory body.”
AstraZeneca’s drug substance facility at Seneffe in Belgium is run by Thermo Fisher Scientific, which declined to comment on the EMA probe. The drug substance facility at Leiden in the Netherlands, run by Halix, is yet to supply vaccine ingredients to the EU as it is still awaiting EMA approval. Oxford BioMedica in the UK, which is also approved to provide drug substance for AstraZeneca in the EU, also declined to comment.
The EMA is expected to issue further findings on Thursday. At a press conference on Tuesday EMA head Emer Cooke said an initial investigation after Austria’s suspension of the ABV 5300 batch had yielded no “plausible” link between that batch of vaccine and the reported adverse events.
“We have been doing some ongoing evaluation of different, additional manufacturing sites,” she said, without providing further details. The EMA declined to comment further.
Catalent also has manufacturing sites in the US, where it fills vials for Johnson & Johnson and Moderna. Earlier this year, it had to resort to checking vials manually for J&J because of a manufacturing issue, which delayed some deliveries.
Additional reporting by Guy Chazan in Berlin, Michael Peel and Sam Flemming in Brussels, and Sarah Neville in London