Matt Smith and Jenna-Louise Coleman will be joined by returning stars David Tennant and Billie Piper for the special, but a BBC source recently told Digital Spy that Christopher Eccleston has chosen not to take part.
McGann - who played the Eighth Doctor - offered his own opinions on the anniversary to ZBTV by suggesting that Eccleston's decision not to appear could mean changes to showrunner Steven Moffat's plans.
"I think Chris Eccleston is probably a big factor in it. I don't want to speak for him... he's probably reluctant to get involved in anything that's ongoing," McGann said.
He continued: "So that's something that they have to somehow get over and deal with. I'm guessing they've got time to do it. It's not quite the anniversary yet. The anniversary doesn't start until November.
"Whatever it is that they're planning and they are making, they've got time to do it. It's my feeling [and] this is just a personal thing, once they resolve Chris Eccleston's participation or non-participation either way, then they're free to [figure it out]... Being actors anyway, they'll call us on the Friday and say, 'You're starting on a Monday'."
McGann then added: "We're not going to know until the 11th hour. Half past 11... I can't count the times as an actor, when [you're] offered something and you start next week!"
Past Doctors Colin Baker and Sylvester McCoy have both recently suggested that they are unlikely to return for the anniversary, with John Barrowman and Freema Agyeman making similar comments.
Doctor Who's 50th anniversary will include several nods to the show's heritage, including bringing back Jemma Redgrave as UNIT's Kate Stewart and a revival for villains the Zygons.
John Hurt has also been cast in an unspecified role in the celebratory episode, which is being filmed now in the UK.
The series continues on Saturday on BBC One in the UK and BBC America in the Mark Gatiss-penned episode 'Cold War'.
Watch Paul McGann discuss the 50th anniversary below: