A method of minimizing headspace between a substance filled in a medical administration barrel and a piston sealing off an open proximal end of the medical administration barrel, the method comprising the steps of: sealingly engaging a vacuum enclosure with the proximal open end of the medical administration barrel, the vacuum enclosure receiving the piston therein; and applying a vacuum to an interior of the sealed vacuum enclosure and medical administration barrel, such that pressure within the sealed vacuum enclosure and medical administration barrel is less than pressure external to the medical administration barrel; physically advancing the piston into the medical administration barrel; and disengaging the vacuum enclosure from the proximal open end of the medical administration barrel, thereby relieving a portion of the medical administration barrel between the piston and the proximal open end of the medical administration barrel from the vacuum and creating a pressure differential across the piston causing the piston to slide further toward the substance in the medical administration barrel and minimizing the headspace between the substance and the piston; characterized in that: the medical administration barrel has at least one groove defining a length extending a distance from the open end of the medical administration barrel toward an opposing distal end of the medical administration barrel, the at least one groove permitting fluid to bypass the piston when positioned along the at least one groove; and the physically advancing step includes physically advancing the piston into the medical administration barrel along the length of the at least one groove, the at least one groove permitting fluid to bypass the piston; and ceasing physical advancement of the piston upon reaching an initial portion of the interior wall of the medical administration barrel free of the at least one groove, thereby sealingly engaging the interior wall of the medical administration barrel and providing an air-tight seal inside a portion of the medical administration barrel between the piston and the distal end of the medical administration barrel and maintaining the vacuum between the piston and the substance positioned within the medical administration barrel. sealingly engaging a vacuum enclosure with the proximal open end of the medical administration barrel, the vacuum enclosure receiving the piston therein; and applying a vacuum to an interior of the sealed vacuum enclosure and medical administration barrel, such that pressure within the sealed vacuum enclosure and medical administration barrel is less than pressure external to the medical administration barrel; physically advancing the piston into the medical administration barrel; and disengaging the vacuum enclosure from the proximal open end of the medical administration barrel, thereby relieving a portion of the medical administration barrel between the piston and the proximal open end of the medical administration barrel from the vacuum and creating a pressure differential across the piston causing the piston to slide further toward the substance in the medical administration barrel and minimizing the headspace between the substance and the piston; characterized in that: the medical administration barrel has at least one groove defining a length extending a distance from the open end of the medical administration barrel toward an opposing distal end of the medical administration barrel, the at least one groove permitting fluid to bypass the piston when positioned along the at least one groove; and the physically advancing step includes physically advancing the piston into the medical administration barrel along the length of the at least one groove, the at least one groove permitting fluid to bypass the piston; and ceasing physical advancement of the piston upon reaching an initial portion of the interior wall of the medical administration barrel free of the at least one groove, thereby sealingly engaging the interior wall of the medical administration barrel and providing an air-tight seal inside a portion of the medical administration barrel between the piston and the distal end of the medical administration barrel and maintaining the vacuum between the piston and the substance positioned within the medical administration barrel. the medical administration barrel has at least one groove defining a length extending a distance from the open end of the medical administration barrel toward an opposing distal end of the medical administration barrel, the at least one groove permitting fluid to bypass the piston when positioned along the at least one groove; and the physically advancing step includes physically advancing the piston into the medical administration barrel along the length of the at least one groove, the at least one groove permitting fluid to bypass the piston; and ceasing physical advancement of the piston upon reaching an initial portion of the interior wall of the medical administration barrel free of the at least one groove, thereby sealingly engaging the interior wall of the medical administration barrel and providing an air-tight seal inside a portion of the medical administration barrel between the piston and the distal end of the medical administration barrel and maintaining the vacuum between the piston and the substance positioned within the medical administration barrel.