Originally Published: 11 AUG 21 04:00 ET

Updated: 11 AUG 21 13:35 ET

By Clare Foran and Ali Zaslav, CNN

(CNN) -- Senate Democrats approved a $3.5 trillion budget resolution early Wednesday morning, setting the stage in the weeks and months to come for the party to craft and attempt to pass a sweeping economic package expanding the social safety net that President Joe Biden has made a signature agenda item without the threat of a filibuster from Republicans who oppose it.

The vote was 50-49 and the measure passed after a lengthy series of amendment votes known as a "vote-a-rama," which started on Tuesday afternoon and went until just before 4 a.m. ET.

The Democratic-controlled House must next take up and pass the budget resolution. Majority Leader Steny Hoyer sent a letter to colleagues Tuesday saying the chamber planned to return the week of August 23 to consider the budget resolution.

Passage of the budget resolution by both chambers will unlock the ability for Democrats to use a process known as budget reconciliation to pass legislation on a party-line vote addressing health care, aid for families, the climate crisis and more. Tuesday's vote is only the first step in what will be a lengthy process. The resolution needs to be approved by both chambers before Democrats can move on to the reconciliation plan, which still must be drafted and will be considered in the fall.

Democrats will need to put together the far-reaching legislative package in such a way so as to ensure the backing of every Senate Democrat from the moderates to the progressives. Senate Majority Leader Chuck Schumer cannot afford to lose a single vote within his caucus in the 50-50 partisan split chamber, where Vice President Kamala Harris can break ties.

The effort to keep every Democrat in line will put leadership to the test, and there are already signs of the major challenge ahead.

Moderate Democratic Sens. Kyrsten Sinema of Arizona and Joe Manchin of West Virginia have pushed back on the bill's price tag, in a warning sign for Democrats that they may have to pare down their bill.

"Given the current state of the economic recovery, it is simply irresponsible to continue spending at levels more suited to respond to a Great Depression or Great Recession -- not an economy that is on the verge of overheating," Manchin said in a statement Wednesday.

Sinema has already said that she does not support a bill that costs $3.5 trillion, though she has signaled she is willing to negotiate.

Returning to the Capitol later Wednesday, Schumer steadfastly refused to say if he would agree to lower the price tag and downplayed Manchin's concerns.

When asked by CNN if he was open to lowering the topline, Schumer said: "Every part of Biden's proposal will be there in a big, robust way. There are some members in our caucus who are less, there are some members in our caucus who are more. We're going to come together to meet that goal."

Asked Wednesday whether the White House views Manchin as a team player in light of his statements, White House press secretary Jen Psaki said, "Absolutely and a key partner to the President."

Manchin's statement, Psaki said, "unintentionally confounded" some aspects of the Biden agenda. Paski described Biden's sweeping social infrastructure agenda as "the cost cutting agenda for working families," and said it will lower costs on childcare, health care, preschool, prescription drugs, college, commuting and household expenses.

"This is also an eight-year investment to make us more competitive," she said. "It's not about putting a huge amount of money into the economy over the next few months, but these are critical investments."

Republicans have denounced the plan as a reckless spending spree for liberal priorities.

Democrats will also be subject to constraints on what they can include under the budget reconciliation process. Provisions have to directly impact the budget, and the Senate parliamentarian may rule that certain priorities cannot be included as a result. The parliamentarian is responsible for advising the chamber on how its rules, protocols and precedents operate.

The budget resolution, which Senate Democrats formally unveiled on Monday, serves as a blueprint for what they expect to include in the far-reaching package and it sets a target date of September 15 for committees to submit their reconciliation legislation.

According to a summary of the resolution, Democrats plan to invest in four major categories: families, climate, health care, and infrastructure and jobs. Among other provisions, the measure seeks to establish universal pre-K for 3- and 4-year-olds and make community college tuition-free for two years. It calls for the establishment of a Civilian Climate Corps, adds new dental, vision and hearing benefits to Medicare coverage and would make a "historic level" of investment in affordable housing. The resolution also aims to lower the cost of prescription drugs and provide "green cards to millions of immigrant workers and families."

Congressional Democrats are pursuing a dual-track strategy to passing major infrastructure and economic legislation and have worked to advance both bipartisan and partisan packages. Earlier on Tuesday, the Senate passed a $1.2 trillion bipartisan infrastructure bill following painstaking and drawn-out negotiations between a bipartisan group of senators and the Biden administration. The push to pass a separate legislative package on a party-line vote will allow Democrats to enact key Biden priorities left out of the bipartisan deal that go beyond the traditional definition of physical infrastructure.

The Senate Budget Committee says the investments of the reconciliation package will be fully offset by a combination of new tax revenues, health care savings and long-term economic growth. The instructions also list corporate and international tax revisions and Internal Revenue Service tax enforcement as options -- both of which Republicans shot down in the bipartisan infrastructure bill. A memorandum to Democratic senators sent Monday specifies that new taxes on families making less than $400,000 a year, small businesses and family farms would be prohibited.

This story has been updated with additional developments Wednesday.