Pacific Rim trade ministers have failed to clinch a deal to free up trade between a dozen nations after a dispute flared between Japan and North America over cars, New Zealand dug in over dairy trade and no agreement was reached on monopoly periods for next-generation drugs.

Trade ministers from the 12 nations negotiating the Trans-Pacific Partnership (TPP), which would stretch from Japan to Chile and cover 40 percent of the world economy, fell just short of a deal on Friday at talks on the Hawaiian island of Maui.

"We have made significant progress during the last week's meetings," US Trade Representative Michael Froman said. "We have advanced towards the conclusion."

The result frustrated negotiators who had toiled to cross off outstanding issues and made significant progress on many controversial issues.

Three sources involved in the talks told the Reuters news agency that a last-minute breakthrough had been viewed as unlikely due to issues with dairy and auto trade and a standoff over biologic drugs made from living cells.

Australian Trade Minister Andrew Robb said the problem lay with the "big four" economies of the United States, Canada, Japan, and Mexico. "The sad thing is, 98 percent is concluded," he said.

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Failure to seal the agreement is a setback for US President Barack Obama, given the trade pact's stance as the economic arm of the administration's pivot to Asia and an opportunity to balance out China's influence in the region.

The talks, which drew about 650 negotiators, 150 journalists and hundreds of stakeholders to Maui, had been billed as the last chance to get a deal in time to pass the US Congress this year, before 2016 presidential elections muddy the waters.

The deal seeks to meld bilateral questions of market access for exports with one-size-fits-all standards on issues ranging from workers' rights to environmental protection and dispute settlement between governments and foreign investors.