The NFL and the players' union did not reach a final agreement on proposed changes to the league's drug policy by Saturday afternoon, meaning suspended players potentially eligible for reinstatement -- like Denver Broncos receiver Wes Welker -- will not play Sunday.
The NFLPA voted Friday to accept a new policy that would implement testing for human growth hormone and significantly increase the threshold for positive marijuana tests.
But despite the union's approval, the deal still had not been finalized due to "significant unresolved issues," according to NFL spokesman Greg Aiello.
"We have not yet reached an agreement with the union," Aiello said Friday. "There continue to be significant unresolved issues."
An agreement needed to be in place by Saturday's 4 p.m. ET roster deadline in order for Welker and Dallas Cowboys cornerback Orlando Scandrick, who both received four-game suspensions, to play in Week 2.
"We hope to have final agreements, including effective date for players with adjusted discipline, very soon," the NFLPA said in a statement released earlier Saturday.
Coach John Fox and quarterback Peyton Manning were among the many members of the Broncos who had hoped Welker would play in Sunday's showdown against the AFC West rival Kansas City Chiefs. Denver even left an opening on its 53-man roster for Welker, who also had been attempting to return from a concussion suffered in the preseason.
Testing for HGH was originally agreed upon in 2011, but the players have balked at the science in the testing and the appeals process for positive tests. If the proposal they voted on Friday is put into action, testing would begin for this season.
The player reps also approved an increase for the threshold for positive marijuana tests from 15 nanograms per milliliter to 35 ng/ml.
Overall changes are retroactive for players suspended under previous policies, as well as for those in the appeal process. Those players, including Welker, Scandrick and Cleveland Browns receiver Josh Gordon (suspended for the season) are subject to standards of the new policies.
Welker and Scandrick both were suspended for amphetamine use in the offseason, but punishment for that is being switched from the performance enhancers policy to the substance abuse program -- except for in-season violations. A two-game suspension would be issued for a player convicted of driving under the influence. But an NFL proposal to immediately suspend a player, owner, coach, team executive or league employee for a DUI arrest was rejected by the union.
ESPN NFL Insider Chris Mortensen and The Associated Press contributed to this report.