PERTH, Australia – Australia’s Therapeutic Goods Administration (TGA) has approved Australian manufacture of Astrazeneca plc’s COVID-19 vaccine (ChAdOx1-S), which is being manufactured by CSL Ltd.

In February, the TGA granted provisional approval to the overseas-manufactured Astrazeneca vaccine. Initial supply of the vaccine was imported into Australia, and now ongoing supply will be manufactured in Australia. CSL has a contract to manufacture 50 million doses of the Astrazeneca vaccine, which the majority of Australia’s population will receive.

The TGA cleared Pfizer Australia Pty Ltd.’s COVID-19 vaccine, branded Comirnaty, in January, and most front-line workers have received the Pfizer vaccine as part of Australia’s phase IA rollout. The TGA acquired 142,000 doses of the Pfizer vaccine.

“We're really excited about the fact we have local manufacturing capability here in Australia, partnering with our partners CSL Seqirus, to manufacture almost 50 million doses of the vaccine right here on shore,” said Liz Chatwin, Astrazeneca’s president for Australia and New Zealand, during a March 23 media briefing.

“This vaccine now will be the main one that most Australians receive. We're probably one of a handful of countries that actually have local onshore manufacturing,” she said, and first doses are expected to be released “imminently.”

Establishing Australian manufacture of the Astrazeneca vaccine by CSL “has involved extensive work by both industry and the TGA over the last six months,” the TGA said, noting that specific TGA approval of Australian manufacturing was required to ensure that the locally manufactured vaccine had “the same composition and performance as overseas-manufactured vaccine, was made to the same quality and is free of contaminants.”

The vaccine is being manufactured at two sites in Melbourne: CSL-Behring Australia in Broadmeadows is manufacturing the active raw vaccine material, while the final vaccine doses are being manufactured, with vials filled and packaged at CSL’s Seqirus plant in Parkville. Quality control testing of the raw material and product is also being carried out in those facilities.

The final step for the Australian-manufactured vaccine is TGA batch release, which is required for “each and every batch of any vaccine supplied in Australia,” the TGA said. That process involves a review of documents supplied by the sponsor describing how the vaccine batch was made, tested, shipped and stored as well as TGA's in-house laboratory testing to ensure the vaccine has been manufactured according to required standards.

Australia’s rollout just getting started

The TGA anticipates that the first batches will be released in the next few days.

More than 1,000 general practices will join the COVID-19 vaccination program beginning March 24. These clinics have initially been supplied with imported Astrazeneca vaccine. Clinics will progressively increase in number to more than 4,000 by the end of April.

There has been some criticism that Australia is failing to meet its vaccine rollout targets and that the rollout has been slow.

Paul Griffin, director of Infectious Diseases at Mater Health Services and associate professor of Medicine at the University of Queensland, acknowledged that the government isn’t hitting its initially proposed targets, but he also said that this is “one of the most complex logistical undertakings that we've ever done,” and “we want to make sure we get this right.”

“Obviously, there's training and other things that need to be implemented. And, obviously, there's also been some supply issues outside of our control, which is why having locally manufactured product is obviously so critical.”

Astrazeneca’s Chatwin stressed that it has only been a year since Australia first closed its borders due to the COVID-19 pandemic, and that it was only in April that Astrazeneca announced its partnership with Oxford.

Australia is planning a 12-week interval between the two shots, which is the same schedule that the U.K. is choosing to follow.

It appears that the immune response gets stronger as the window between the two doses is longer than eight weeks, said Mene Pangalos, Astrazeneca’s executive vice president for Biopharmaceuticals R&D.

“I think the data clearly supports a longer dose interval,” concurred Griffin. “And while some people are saying 12 weeks is going to be difficult logistically, I think having the flexibility there will enable us to cope with a number of different situations.”

“In Australia, we're very fortunate our situation is under control at the moment, but as we've seen in many countries, that can potentially change, so I think the flexibility there makes sense.”

Astrazeneca is already working on next-generation variants, and clinical trial results should start to roll in by early spring next year, said Pangalos.

And in terms of regulatory requirements for the new variants, companies won’t need to conduct vaccine efficacy studies but instead will need to show compatibility in terms of immune response and the ability to neutralize both the new variants and existing variants, he said.

“In terms of supply chain, the good news is the supply chains are up and running now around the world, so it becomes a matter of deciding which vaccine you want to make and either switching one out for the other, or having … two vaccines running in parallel, but the process will be the same as it is for the current ChAdOx vaccine that we have going.”

When asked about adverse events with respect to the ChAdOx vaccine, Pangalos said that both the EMA and the U.K.’s Medicines and Healthcare products Regulatory Agency concluded that there was no cause to think that the vaccine was causing blood clots. Both regulators “agreed that there was no signal and that we should continue to vaccinate with our vaccine around the world.”

“But it's important that we continue to monitor safety signals, understand them, and continue to give the public confidence that the vaccines are safe,” he added. “That will never stop. In one year, two years, three years, we will always continue to monitor for signals ... And the regulators will demand it.”

The TGA also released a statement outlining that it believes the link with the receipt of the vaccine and those events has not been confirmed, “yet they are continuing to closely monitor, as they do with all such events,” Griffin said. “It would clearly not be in anyone’s interest to recommend a vaccine in which they were not genuinely completely confident in its safety, whether that be the manufacturer or relevant regulators.”

When questioned about the U.S. phase III results that were recently reported, Pangalos said that interim results were called “because we had a very convincing set of data, and so the independent board that was reviewing the data wanted us to be unblinded. The results that we will ultimately submit to the FDA … will be the full primary analysis, but with the 141 events that we have as the interim, we have a highly positive study.”

“The results aren't going to change,” he said. “We have a vaccine that demonstrated 79% efficacy in the population against symptomatic disease. It showed 80% vaccine efficacy in the over 65s. And they had 100% efficacy against severe COVID disease and hospitalizations.”