Method of manufacturing, sterilisation and filling of flexible pouches, comprising the subsequent steps of: - in a site of a producer subject, producing a plurality of pouches, wherein each pouch comprises a container body formed by walls made of flexible film and a spout comprising an entrance portion with an inlet and a tube with an outlet, said spout being sealingly applied to the container body so as to protrude outside of it with at least a section of the tube; - providing a plurality of sacrificial closures reversibly applicable to the outlet mouth of the spout; - applying the sacrificial closure to the outlet of the spout, thereby obtaining provisionally closed non-filled pouches to be sterilised; - loading a plurality of provisionally closed non-filled pouches to be sterilised on a transport device for collective transport; - forming a transport group, containing a plurality of transport devices, each carrying the provisionally closed non-filled pouches to be sterilised, stacked; - transporting the transport group from the site of the producer subject to a site of a steriliser subject or a filler subject that also performs sterilisation; - performing a sterilization of the entire transport group loaded with provisionally closed non-filled pouches, by ionising radiation; - picking the sterilised provisionally closed non-filled pouches from the transport group and sending them in succession to a sterile chamber of a filling machine; - for each sterilised provisionally closed non-filled pouch, making at least a portion of the tube provided with the sacrificial closure to pass through the sterile chamber; - during said passing through of the sterile chamber, separating the sacrificial closure from the tube, filling the sterilised open pouch and applying a tamper-proof cap to the tube to close the pouch. - in a site of a producer subject, producing a plurality of pouches, wherein each pouch comprises a container body formed by walls made of flexible film and a spout comprising an entrance portion with an inlet and a tube with an outlet, said spout being sealingly applied to the container body so as to protrude outside of it with at least a section of the tube; - providing a plurality of sacrificial closures reversibly applicable to the outlet mouth of the spout; - applying the sacrificial closure to the outlet of the spout, thereby obtaining provisionally closed non-filled pouches to be sterilised; - loading a plurality of provisionally closed non-filled pouches to be sterilised on a transport device for collective transport; - forming a transport group, containing a plurality of transport devices, each carrying the provisionally closed non-filled pouches to be sterilised, stacked; - transporting the transport group from the site of the producer subject to a site of a steriliser subject or a filler subject that also performs sterilisation; - performing a sterilization of the entire transport group loaded with provisionally closed non-filled pouches, by ionising radiation; - picking the sterilised provisionally closed non-filled pouches from the transport group and sending them in succession to a sterile chamber of a filling machine; - for each sterilised provisionally closed non-filled pouch, making at least a portion of the tube provided with the sacrificial closure to pass through the sterile chamber; - during said passing through of the sterile chamber, separating the sacrificial closure from the tube, filling the sterilised open pouch and applying a tamper-proof cap to the tube to close the pouch.