Hillary Rodham Clinton declared her opposition to the Trans-Pacific Partnership trade accord on Wednesday, her most significant break with President Barack Obama since launching her campaign for the Democratic presidential nomination. 

"I think there are still a lot of unanswered questions," she said of the big trade deal in an interview with PBS' "Newshour." "As of today, I am not in favor of what I have learned about it." 

Her push-back against the chief economic proposal of Obama's second term is a blow to the president, undermining his arguments to Congress as the White House is in the final stretch of winning approval of a deal years in the making. 

Clinton joins the rest of the Democratic field in challenging a trade pact that's enraged the labor unions, environmentalists and other liberal constituencies whose support will be crucial to her electoral success. 

Her position on the agreement also marks a striking reversal for the former secretary of state, who promoted the deal in dozens of appearances during Obama's first term in office. During a 2012 trip to Australia, she called it the "gold standard in trade agreements." 

In the interview, she said the agreement does not meet her standard for creating jobs, raising wages and protecting national security. Clinton raised specific concerns about a potential for currency manipulation by China and provisions that she said would benefit pharmaceutical companies at the expense of patients. 

"I don't believe it's going to meet the high bar I have set," she said. 

The united opposition from the Democratic presidential field leaves Obama in the uncomfortable position of watching a Democratic debate next week in which none of the major candidates is willing to defend a deal that the White House sees as a key piece of his presidential legacy. 

Obama and many Republican lawmakers favor the accord, saying it will greatly help the U.S. economy by boosting exports of American products. 

Clinton's campaign and the Obama administration have always said the time would come when she would outline her own policies and deliver criticisms, implied and direct, of the president. 

"I am not running for my husband's third term or President Obama's third term," Clinton told voters in Davenport, Iowa, on Tuesday, repeating a frequent line from her campaign speeches. 

"I'm running for my first term." 

 Last month, she came out against the Keystone XL pipeline, which would carry oil from Canada to the U.S. Gulf Coast; the administration remains undecided. 

In August, she said Obama's decision to approve offshore drilling in the Arctic wasn't "worth the risk" to the environment. She subtly resurrected her 2008 primary attack of Obama's approach to world affairs, taking a more hawkish stance toward Russia, Syria and Iran. And she's promised to work to repeal the "Cadillac tax," a tax on high-cost employer-sponsored insurance that the Obama administration says is necessary to fund the health care law. 

On both immigration and gun control, she has also pledged to use executive power as president to do more than Obama. 

On immigration, she cited Obama's deportation policy this week and said, "I'm not going to be breaking up families. And I think that is one of the differences." 

Still, she added, "I totally understand why the Obama administration felt as though they did what they did under the circumstances." 

Campaign veterans in the White House say the impact of Clinton's departures from Obama policies are minor and they dismiss some of her proposals as routine campaign fodder. Candidates use policy plans to declare their priorities. Worries over practical implementation come later. 

Clinton aides know she must tread lightly when it comes to criticizing Obama, given that much of her strategy relies on the still-loyal coalition of African-Americans, Latinos, women and younger voters that twice elected Obama. But at the same time, they say she must find ways to distinguish herself -- and undercut Republican attacks that Clinton would simply provide a third Obama term. 

Many of Clinton's top aides joined her campaign from the White House and the two staffs remain in frequent communication. 

Before Clinton announced her opposition to the Keystone pipeline and gun proposals, campaign staff alerted the White House. After Obama last week appeared to deride her proposal for a no-fly zone over Syria, aides called to make sure Clinton understood the criticism wasn't aimed at her, according to a senior White House official who spoke on condition of anonymity to discuss private conversations. 

The White House doesn't deny that Clinton's new distance has sometimes created awkwardness for the president. 

On immigration, Clinton's promise to go further than Obama in using executive authority to ease the threat of deportation for immigrants living illegally in the U.S. contradicts Obama's assertion that he's done all he can under the law. 

Similarly on gun control, just days after Obama said "this is not something I can do by myself," Clinton seemed to think otherwise. She promised to close the "gun-show loophole" through executive action.