Wentworth Miller jokingly admits he was nervous about his character Chris Redfield being similar to his Prison Break (2005) character Michael Scoffield: in both cases, he is in a prison and his first lines are "I know a way out of here".
The weird creatures with the flower-like mouths are called majini. They are lifted directly from the game Biohazard 5 (2009). It is interesting to note that in the game, the majini are not the result of infection with the T-virus, but with a parasitic organism. The movie does not provide an explanation for their different appearance.
The original plan was to have some brief flashback sequences which would elaborate on the backstory of Chris and Claire Redfield, and reveal the ongoing search of the two siblings to find one another. This is a storyline well established in the video games, where Claire Redfield comes to Raccoon City to search for Chris in Resident Evil 2 (1998), but doesn't meet up with him until Resident Evil Code: Veronica X (2000). The idea was scrapped.
After seeing footage of James Cameron's Avatar (2009), Paul W.S. Anderson was sold on the idea of making the film in 3D. He and his crew spent two weeks in pre-production learning how to properly use the 3D camera system.
The back-story reveals that the trip of Claire and K-Mart from Nevada to Alaska took a lot longer than they had anticipated. When Alice finds the abandoned chopper and reads the diary, there are notes written by K-Mart describing their course. They made many stops for refueling and new supplies and they eventually arrived at Alaska a few days before Alice.
This marks the fourth time that Paul W.S. Anderson has written the script for a Resident Evil movie. He has written all of them since the first one. This also marks the second time Anderson has directed a Resident Evil movie, something no other director has done. In an interview, Anderson stated that his dissatisfaction with Mortal Kombat: Annihilation (1997) (with which he had no affiliation) had led to him stay with the Resident Evil franchise, so that he could be responsible for how future movies turned out.
The opening scene in the movie is quite symbolic - all people are carrying umbrellas in the rain except the zombie girl. "Umbrella" is also the name of the corporation who is responsible for the creation and spread of the T-Virus, on which the main plot of the Resident Evil series is based.
The only film in the series to feature Chris Redfield, a character from the video games. Ironically, Chris is one of the most featured elements in the games, showing up as a playable character in six of the main series games (as of 2018, not including remakes and spin-offs).
The sequence in Tokyo after the helicopter crash was extended. According to the script, Alice would search through the debris and would discover the body of Albert Wesker. She would shoot him repeatedly to ensure he died. After Alice left, Wesker's body would begin to regenerate and even start forming the majini mouth.
This was the first film to feature Smith and Wesson's new .460 Magnum revolver, which replaced the .454 Casul as the second most powerful production handgun in the world after the .500 Smith and Wesson Magnum.
The trivia items below may give away important plot points.
The superspeed that Albert Wesker manifests as well as his grudge against Chris and Claire Redfield are elements from the video games. His climactic fight with the Redfield siblings is an almost shot-by-shot reenactment of a scene directly from the game.
The intention of writer/director Paul W.S. Anderson was that this would be the first film in the series to have an optimistic ending. The producers, however, wanted an intense cliffhanger as the ending. The director added the massive attack, leaving the film open ended.
Despite prominent billing for actress Spencer Locke, her screen time is very limited since she appears briefly at the end. Additionally, the character of K-Mart does not utter a single line of dialogue during the entire film (excluding archive footage from Resident Evil: Extinction (2007)).
First film where Chris and Jill are both present. However Chris and Jill never meet or share any scenes in the film, unlike the Resident Evil games where the two are very close. In fact the couple have worked together in Resident Evil (1996), Baiohazâdo reberêshonzu (2012) and Biohazard 5 (2009).
Chris and Claire confronting Wesker is slightly reminiscent of Resident Evil Code: Veronica X (2000). Coincidently Wesker first shows his superhuman powers in Code Veronica to Chris and Claire same as in this film Wesker first uses his powers on Chris and Claire in the films.
Jill Valentine (Sienna Guillory), who shows up in the mid-credits scene, is being manipulated through a device she is wearing on her chest. The same thing happened to Jill in the game Biohazard 5 (2009).
Claire Redfield (Ali Larter) running away from the axe-wielding BOW as it slashes at her and breaks down much of the surrounding is a visual reference to Resident Evil Code: Veronica X (2000). In that game, Claire runs away from a mutated Steve as he tries to hit her with his axe.