Kurt Busiek created the Madame Masque bio-duplicates during the Nefaria Protocols storyline. He used them as a means to retcon most of Madame Masque's prior appearances that he didn't like or which didn't serve his story and killed most the duplicates off. One of the big factors of the retcon was the reveal that the Madame Masque who had joined the Avengers some years previously was one of the engineered clones who also wound up dying.

The retconned first appearance of a Madame Masque duplicate is in Iron Man #129 and almost every Madame Masque appearance between 1977 and 2000 has been attributed by Busiek to a bio-duplicate.