A method of manufacturing a prefilled drug delivery device of the type comprising a housing (10, 110) extending along a longitudinal axis and having a guide structure (13, 113) fixed therein, a variable volume drug reservoir (60, 160) having a displaceable wall (62, 162), a piston rod member (20, 22, 120, 122) extending through the guide structure (13, 113) and comprising a distal end portion adapted to interface with the displaceable wall (62, 162), and a piston rod guide (40, 140), wherein the piston rod member (20, 22, 120, 122) is operatively coupled with the piston rod guide (40, 140) and configured to undergo axial or helical motion through the guide structure (13, 113) in response to a rotation of the piston rod guide (40, 140) relative to the housing, the method comprising: (i) arranging the piston rod member (20, 22, 120, 122) and the piston rod guide (40, 140) in the housing (10, 110) such that ∘ the piston rod member (20, 22, 120, 122) extends through the guide structure (13, 113), and the distal end portion is in an initial assembly position, and ∘ the piston rod guide (40, 140) surrounds a portion of the piston rod member (20, 22, 120, 122) proximally of the guide structure (13, 113), and is in a first state being capable of bi-directional rotation with respect to the housing (10, 110), where rotation of the piston rod guide (40, 140) in a first direction relative to the housing (10, 110) causes distal movement of the piston rod member (20, 22, 120, 122) relative to the guide structure (13, 113), and vice versa, and rotation of the piston rod guide (40, 140) in a second direction relative to the housing (10, 110) causes proximal movement of the piston rod member (20, 22, 120, 122) relative to the guide structure (13, 113), and vice versa, (ii) subsequent to (i) bringing the displaceable wall (62, 162) of the variable volume drug reservoir (60, 160) into abutment with the distal end portion of the piston rod member (20, 22, 120, 122), characterised by (iii) subsequent to (ii) moving the variable volume drug reservoir (60, 160) proximally relative to the housing (10, 110) to a completely mounted position, thereby moving the distal end portion to a final assembly position proximally of the initial assembly position, and (iv) subsequent to (iii) bringing the piston rod guide (40, 140) irreversibly to a second state in which rotation of the piston rod guide (40, 140) in the second direction relative to the housing (10, 110) is prevented by a unidirectional ratchet mechanism. (i) arranging the piston rod member (20, 22, 120, 122) and the piston rod guide (40, 140) in the housing (10, 110) such that ∘ the piston rod member (20, 22, 120, 122) extends through the guide structure (13, 113), and the distal end portion is in an initial assembly position, and ∘ the piston rod guide (40, 140) surrounds a portion of the piston rod member (20, 22, 120, 122) proximally of the guide structure (13, 113), and is in a first state being capable of bi-directional rotation with respect to the housing (10, 110), where rotation of the piston rod guide (40, 140) in a first direction relative to the housing (10, 110) causes distal movement of the piston rod member (20, 22, 120, 122) relative to the guide structure (13, 113), and vice versa, and rotation of the piston rod guide (40, 140) in a second direction relative to the housing (10, 110) causes proximal movement of the piston rod member (20, 22, 120, 122) relative to the guide structure (13, 113), and vice versa, ∘ the piston rod member (20, 22, 120, 122) extends through the guide structure (13, 113), and the distal end portion is in an initial assembly position, and ∘ the piston rod guide (40, 140) surrounds a portion of the piston rod member (20, 22, 120, 122) proximally of the guide structure (13, 113), and is in a first state being capable of bi-directional rotation with respect to the housing (10, 110), where rotation of the piston rod guide (40, 140) in a first direction relative to the housing (10, 110) causes distal movement of the piston rod member (20, 22, 120, 122) relative to the guide structure (13, 113), and vice versa, and rotation of the piston rod guide (40, 140) in a second direction relative to the housing (10, 110) causes proximal movement of the piston rod member (20, 22, 120, 122) relative to the guide structure (13, 113), and vice versa, (ii) subsequent to (i) bringing the displaceable wall (62, 162) of the variable volume drug reservoir (60, 160) into abutment with the distal end portion of the piston rod member (20, 22, 120, 122), characterised by (iii) subsequent to (ii) moving the variable volume drug reservoir (60, 160) proximally relative to the housing (10, 110) to a completely mounted position, thereby moving the distal end portion to a final assembly position proximally of the initial assembly position, and (iv) subsequent to (iii) bringing the piston rod guide (40, 140) irreversibly to a second state in which rotation of the piston rod guide (40, 140) in the second direction relative to the housing (10, 110) is prevented by a unidirectional ratchet mechanism.