(at around 59 mins) The line that Inmate 333 says while they are all watching The Human Centipede films, "this trash belongs to a world where stars don't shine" was originally written by Roger Ebert in his review for The Human Centipede (First Sequence) (2009).
Dieter Laser and Laurence R. Harvey, who played the villains from the first and second movies, appear here as different characters.
Although it was promoted as the final installment of the series, and with Tom Six even stating that he saw the films as a trilogy, he mentioned he is open to a fourth film, focusing on the Human Caterpillar concept shown in this film. While promoting The Onania Club, Six confirmed that he was developing a new film based on the Human Caterpillar.