In a recent comment, Ben Todd of 80,000 Hours wrote about his desire to see more EA entrepreneurs who can scale their charities to spend larger amounts of money:
I'm especially excited about finding people who could run $100m+ per year 'megaprojects', as opposed to more non-profits in the $1-$10m per year range, though I agree this might require building a bigger pipeline of smaller projects.
He later tweeted
It's striking that the projects that were biggest in pre-2015 (OP, GiveWell, MIRI, CEA, 80k, FHI) are still among the biggest today, when additional resources should make new types of project possible.
It is striking and surprising that these are still some of the largest projects in the EA community. However, it's not surprising that these types of projects aren't spending $100 million or more each year. Other than regranting, GiveWell's largest expense in 2020 was staff salaries - they spent just over $3 million on salaries. In total, they spent about $6 million (excluding regranting). GiveWell would have to grow to 20x the size in order to become a $100 million 'megaproject' .
It is very hard for a charity to scale to more than $100 million per year without delivering a physical product. If you spend half your money on staff, like GiveWell, and spend on average $200,000 per employee including benefits and anything you owe to the government, you'd still need at least 250 employees. In comparison to GiveWell's $6 million in expenditure, the Against Malaria Foundation spent $65 million in 2020 on delivering bednets.
It makes intuitive sense that charities that deliver something tangible should spend more than charities with primarily desk-based staff, and that charities that deliver tangible benefits while remaining competitively cost-effective are particularly valuable, but most EA charities focus on desk-based work. By my count, 8 of the 13 charities incubated by Charity Entrepreneurship are focused entirely on research or advocacy, with the rest focused on other low-cost interventions like purchasing radio ads or sending text messages. These charities are good and I'm glad that they exist! And when we're focusing on cost-effectiveness, one of the best ways to achieve a good cost-benefit analysis is lowering costs. However, few of them seem likely to scale to a $100 million megaproject.
If EA wants to spend larger amounts of money cost-effectively, we will need to start identifying or founding charities with physical aspects to them. Some examples suggested are researching vaccines for neglected diseases (or researching how to speed up developing vaccines for novel viruses) or the Sentinal system for identifying new diseases. For more examples in the global poverty and climate space, the types of initiatives the Gates Foundation tend to invest in might be instructive -for example, developing low-carbon cement or gene-editing mosquitoes.
Being an executive at a charity that delivers a tangible product requires different skills to running a research or advocacy charity. A smaller charity will likely need to recruit all-rounders who are pretty good at strategy, finance, communications and more. In contrast, in a $100 million you will also need people with specialized skills and experience in areas like negotiating contracts or managing supply chains. If you want to start or join an EA charity that can scale to $100 million per year, you should consider developing skills in managing large-scale projects in industry, government or another large charity in addition to building relationships and experience within the EA community.
In summary, charities are more likely to be 'megascalable' if they involve staff doing something other than sitting at a desk, so if you're keen to lead a huge EA project consider developing delivery skills that are rarer in the EA community.
 The technical definition of 'megaproject' in the academic literature is unrelated to what Ben's talking about here - he's simply talking about very large projects.