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Gamble previously confirmed that the new episodes would see Sam (Jared Padalecki) and Dean (Jensen Ackles) battle "more monsters".
She has now told Entertainment Weekly that the brothers will begin investigating why the creatures have begun acting strangely.
"Sam and Dean are looking into the fact that monsters are acting off-pattern," said the showrunner. "It's sort of a post-apocalyptic landscape and monsters are acting in various weird ways. It's a monster mystery."
Gamble previously revealed that a forthcoming episode of Supernatural would reference the Twilight saga and other vampire-based series. She explained that she had been working on the instalment alongside creator Eric Kripke.
"I was just doing a bit of work on the script today with Eric," she said. "There are a lot of references to Twilight and... The Vampire Diaries."
Supernatural returns to The CW on September 24.
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