NSW Health Minister Brad Hazzard visited the worksite on Tuesday to check the project's progress after unveiling the latest designs for the "centrepiece" of the $780 million John Hunter Health and Innovation Precinct.

Minister Hazzard said plans for a new seven-storey acute services building at the John Hunter Health and Innovation Precinct site had been lodged with the Department of Planning, and "preliminary work" could begin on the site by the end of the year.

"There is no question that this is three quarters of a billion dollars of the best spent money the Hunter will ever see," he said.

"To develop a new facility worth $780 million is a massive job. It is a very challenging site. We know it's on a ridge, and there was always some concerns about what we could actually do here in a synergistic way."

But Minister Hazzard said that while the design of the facility had "no doubt proved a challenge", he felt the new building would be something the community would be "very proud of".

The development of the John Hunter and John Hunter Children's Hospital's "clinical tower" would mean a 60 per cent increase in intensive care capacity, and almost 50 per cent more theatres.

The building will include a new emergency department, critical care services for adults and paediatrics, operating theatres, imaging services, birthing suites and a neonatal intensive care unit and special care nursery.

The development would "improve" the internal road network and eventually connect to the Newcastle Inner City Bypass. It would also have a rooftop helipad and more parking.

Minister Hazzard said they were continuing to investigate possible sites for Newcastle's mass COVID-19 vaccination hub.

"On the issue of COVID and the vaccines, I am really concerned that some of the community think it's OK to sit on our haunches and not get the vaccine," Minister Hazzard said.

"You really need to get it, and the five cases that have just broken out in Melbourne are a reminder of the danger of this virus. It is a deadly virus and we can't afford to sit back and wait."

Minister Hazzard said they hoped to have firmed up a mass vaccine site in Newcastle within the next month.

It may take "another seven" weeks to fit out the venue, and the site could be required for "at least a year or two, possibly three" to administer both AstraZeneca and Pfizer vaccines.

"The odds of you getting ill or dying if the virus breaks out here are far greater than the odds of you having a problem with the AstraZeneca or Pfizer vaccine," he said.

"When we walk around in our society, where we've managed to look after the community fairly well in all states... we tend to live in a fool's paradise.

"It is extremely dangerous, it is out there, it is more rampant than it has been at any point - and we need to be on high alert for quite a while."

Hunter New England Health chief executive, Michael DiRienzo, told the Newcastle Herald they hoped to have a shortlist of vaccine sites "in the next week or so".

"We'd like to have it operational as soon as possible," he said.

"We have looked at some of the sites recommended by local business people and the community," he said. "We are just working out the details."

Mr DiRienzo confirmed they have considered setting up the hub at McDonald Jones Stadium, as well as other sites suggested by businesses and the local community.

But given the vaccine centre may be required for more than a year, or even up to three years, the decision was not as simple as choosing a big space with lots of parking.

"When we look at stadiums and other venues where they are entertainment-based, we then have to come up with a way of being able to leave for a few days so they can use the facility, and come back," Mr DiRienzo said.

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