Head coach Eddie Jones has named 12 uncapped players in a much-changed England training squad for this autumn's internationals.
Players from six of the Premiership's 12 teams were unavailable for selection because of league commitments.
The 28-man squad will meet for a three-day training camp on Tuesday.
England face the Barbarians on 25 October, before completing the 2020 Six Nations against Italy and then playing four games in the Autumn Nations Cup.
Northampton scrum-half Alex Mitchell, Harlequins number eight Alex Dombrandt and Northampton lock David Ribbans are among the 12 uncapped players named.
"Our preparation to build the team for the Italy game starts now," Jones said.
"We'll be slowly building up, working on the basics and working on team cohesion. We're excited to be back together in camp representing England."
Players from Exeter, Wasps, Bristol, Bath, Sale and Worcester are not included in Jones' first training squad since the pandemic paused the 2020 Six Nations in March.
Sale's game against Worcester has been moved to Wednesday after the club recorded 19 positive coronavirus cases but there are doubts it will go ahead.
If Sharks win that game, they will make it to the play-offs instead of Bath. Exeter, Wasps and Bristol have already secured their places in the semi-finals which take place on 10 and 11 October.
Another England training squad will be announced after that, with the team meeting again on 15 October.
Bristol and Exeter have European finals to play on 16 and 17 October respectively and the Premiership final takes place on 24 October.
England play Barbarians the next day and the week after will attempt to secure the Six Nations title against Italy.
England should be back to full strength when they play their first match of the Autumn Nations Cup against Georgia at Twickenham on 14 November.
They then play Ireland and Wales, the other two teams in Group A, before facing the side in the equivalent finishing position from Group B, which contains Scotland, France, Italy and Fiji, on 6 December.
New faces step in with big names absent
Locks Courtney Lawes and George Kruis, who both featured in the World Cup final squad last November, are absent. Lawes has an ankle injury and Kruis is joining Japanese side Panasonic Wild Knights in November.
Northampton's South Africa-born second row Ribbans, 25, has been given the opportunity to step up in their wake alongside team-mate Alex Moon, with England regular Maro Itoje also in the squad.
Fellow Saints player Fraser Dingwall is included, with Sale centre Manu Tuilagi ruled out for six months because of a torn Achilles tendon.
Uncapped number eights Dombrandt and Jack Clement join Billy Vunipola in the squad.
But with Bristol tight-head prop Kyle Sinckler unavailable, Leicester's Joe Heyes and Harlequins' Simon Kerrod have been preferred to the more established Jamal Ford-Robinson.
Northampton flanker Lewis Ludlam is unavailable because he is self-isolating.
England squad
Backs: Ali Crossdale (Saracens)*, Elliot Daly (Saracens), Fraser Dingwall (Northampton Saints)*, Nathan Earle (Harlequins)*, Owen Farrell (Saracens), George Ford (Leicester Tigers), Piers Francis (Northampton Saints), George Furbank (Northampton Saints), Willi Heinz (Gloucester Rugby), Joe Marchant (Harlequins), Jonny May (Gloucester Rugby), Alex Mitchell (Northampton Saints)*, Ollie Thorley (Gloucester Rugby)*, Ben Youngs (Leicester Tigers)
Forwards: Jack Clement (Gloucester Rugby)*, Alex Dombrandt (Harlequins)*, Ellis Genge, (Leicester Tigers), Jamie George (Saracens), Joe Heyes (Leicester Tigers)*, Maro Itoje, (Saracens), Simon Kerrod (Harlequins)*, Lewis Ludlow (Gloucester Rugby)*, Alex Moon, (Northampton Saints)*, David Ribbans (Northampton Saints)*, Jack Singleton (Gloucester Rugby), Billy Vunipola (Saracens), Mako Vunipola (Saracens), Mark Wilson (Newcastle Falcons)
*uncapped players