Its sprawling campus in downtown Seattle may still be on the architects’ drawing boards, but the world’s biggest philanthropic foundation is at work on the reconstruction of its own internal processes. The Bill & Melinda Gates Foundation, created by the billionaire co-founder of Microsoft and his wife, had long been the globe’s largest such organisation. Then, in 2006, Warren Buffett, the world’s second richest man, raised the stakes by pledging to double its $29bn endowment. The associated publicity triggered a burst of new interest in giving by wealthy individuals, including a few other direct donations.

But Mr Buffett’s commitment also brought challenges. It increased pressure by adding the condition that the foundation double its spending to $3bn a year by 2009, and stretched the organisation as it struggled to cope with a sharp upswing in demands for support well beyond its administrative capacity, financial ability or strategic objectives.

The higher visibility his pledge provided has brought fresh scrutiny that has slightly dimmed the foundation’s halo, with criticism of a lack of external accountability and transparency. This triggered calls for its corporate investment policies to be brought more in line with its stated philanthropic goals through “mission-related investment”.

There is little doubt that the foundation has done much to stimulate fresh interest in giving by wealthy individuals, sparked wider discussions about philanthropy and begun to deliver results. It has helped promote new, high-profile public debates on education reform, the “neglected” diseases of the poor across the world, and the broader challenges of economic development. One of its single largest recipients, the Global Alliance on Vaccines and Immunisations, claims alone to have saved 2.3m future deaths by protecting against disease.

And it has catalysed new approaches to funding, setting a pioneering example as a non-governmental donor to the UN-backed Global Fund to Fight Aids, TB and Malaria. It has helped promote alternative financial models to tackle market failures, including Advance Market Commitments and a planned Affordable Malaria Facility.

Now, the organisation has started to take steps to respond to its critics. It has split into two legal entities, formally separating the Bill & Melinda Gates Trust Foundation, which invests its endowment, from the Bill & Melinda Gates Foundation, which spends part of it each year.

Mr and Mrs Gates are trustees of both. Mr Buffett has added some external scrutiny by becoming a third trustee of the foundation, but not the trust, which in its most recent filings showed that the Berkshire Hathaway shares pledged so far by Mr Buffett accounted for more than 13 per cent of its equity holdings.

While remaining discreet, the foundation has expressed scepticism about mission-related investment, arguing that it is best to generate the maximum financial returns in order to increase the amount that can then be paid out to further its philanthropic objectives.

But in more recent statements, it has said that the Gateses instruct their managers to vote as proxies “consistent with the principles of good governance and good management”, and to consider in investment decisions “issues beyond corporate profits, including the values that drive the foundation’s work”. Its only explicit bans are on acquiring shares in tobacco companies or those with links to Sudan.

The foundation is also increasingly studying – both directly and through intermediaries that it supports – revolving credit funds and even equity vehicles designed to generate financial returns while fulfilling social objectives.

If investing the money presents difficulties, however, spending it is at least as challenging.

As Patty Stonesifer, chief executive of the foundation, put it in the latest annual report: “Giving away money isn’t hard. Giving it away effectively sure is.”

In efforts to achieve its aim “to help reduce inequities in the United States and around the world”, the foundation has formally split into three divisions, covering global health, global development and the US. Its workforce, now numbering more than 450, is growing fast.

At a strategic level, the foundation has taken steps to respond to the accusation that it is unaccountable to anyone beyond its principal donors. It has unveiled plans for an advisory boards for each of its three divisions, each with half a dozen luminaries appointed for a single three-year term, and meeting twice a year.

It is also beginning to provide more information on its website, including a series of case studies of organisations and activities that it has funded to describe “what is working, and what isn’t”.

One detailed evaluation by the American Institutes for Research of the foundation’s programmes to improve US schools has been published. It concluded that students had achieved better English results but worse scores in mathematics. Similar reports in other areas have not been made public so far.

The greatest challenge for the foundation remains how far it can get in achieving its objectives. It has long argued that it is aiming to solve problems, not simply to provide charity, and it has added to the urgency by committing to spending its entire endowment within 50 years of the Gateses’ lifetimes.

However, with the slow pace of pharmaceutical and vaccine development, for instance, it is only now that a number of the projects that the foundation has supported since the turn of the millennium are moving towards later-stage clinical trials. Recent failures of HIV vaccines and microbicides have highlighted the significant scientific challenges in meeting some of its most ambitious health goals. Any products that win regulatory approval will still need to reach those who need them most, including the poorest people living in the most inaccessible places. And such challenges will require ever more money, far beyond the capacity of the foundation alone.

Yet other donors have been slow to respond, whether because of financial restrictions, suspicion towards particular projects, the relative merits of alternative causes, such as global warming, or a belief that the Gates Foundation has already provided enough support for everyone.

For instance, a report in November by the Treatment Action Group, an advocacy organisation, to trace support for new research into vaccines, diagnostics and drugs for tuberculosis highlighted that funding had been almost stagnant during the previous year, with governments’ contributions dropping and much of the shortfall made good by the Gates Foundation.

A similar “displacement” effect may have been behind the decision of Larry Ellison, the billionaire head of software company Oracle, to pull back from support for a research programme at Harvard University into health metrics. The Gates Foundation took up the slack, bringing Christopher Murray, the academic behind it, to Seattle to continue his work.

But such gestures have their limits. Sustainable success will be uppermost on Mr Gates’s desk when he steps down from Microsoft next summer to devote his time more fully to the foundation.