Described is a drug delivery system and method for priming such drug delivery system so that unwanted delivery of a drug is prevented. In one embodiment, a drug delivery system is provided that includes a drug infusion pump and a cartridge configured for insertion into the drug infusion pump. The cartridge includes a hollow barrel for receiving and storing a drug and a plunger having a first end and a second end. The first end of the plunger is slidably insertable and movable within the barrel. The second end of the plunger is slidably insertable and movable with a chamber of the drug infusion pump. The second end of the plunger also includes an interlock that is passively engaged by a piston within the drug infusion pump during priming to prevent unwanted delivery of the drug.