Blow-fill-seal machines

Figure 3.29. Photographic representation of a blow-fill-seal machine, which can be particularly useful in the aseptic filling of liquid products (refer to text for details). While used fairly extensively in facilities manufacturing some traditional parenteral products, this system has not yet found application in biopharmaceutical manufacture. This is due mainly to the fact that many biopharmaceutical preparations are sold not in liquid, but in freeze-dried format. Also, some proteins display a tendancy to adsorb onto plastic surfaces. Photo courtesy of Rommelag a.g., Switzerland...

Form/Fill/Seal Machine Targets Bottle Blow Molding, MP, June 2003. 

Blow/fill/seal units are purpose built machines in which, in one continuous operation, containers are formed from a thermoplastic granulate, filled and then sealed, all by the one automatic machine. Blow/fill/seal equipment used for aseptic production which is fitted with an effective grade A air shower may be installed in at least a grade C environment, provided that grade A/ clothing is used. The environment should comply with the viable and non-viable limits at rest and the viable limit only when in operation. Blow/fill/seal equipment used for the production of products for terminal sterilisation should be installed in at least a grade D environment... 

Two process variants exist. In both, the first step is to provide sterility for the blowing operation, including the air used in forming the container. In the blow and hold process, the bottle is sealed in the mold to preserve its sterility, and can then be released into a non-sterile environment. In a subsequent filling operation, it is cut open under sterile conditions, filled, and sealed again. In the blow-fill-seal process, the bottle is blown, filled with product (often while still in the mold), and sealed, all within the sterile environment of the blow molding machine, either at a single station or at multiple stations. 

LDPE is generally used for small volume blow moulded articles, mainly for household, domestic, and pharmaceutical applications. Due to its high purity, LDPE is the preferred raw material for medical and pharmaceutical packaging applications. In the pharmaceutical field, blow moulded articles have a particular importance because they can be filled under sterile conditions immediately after production, while still in the blow moulding machine (blow-fill-seal process). To ensure sterilisation, higher density LDPE is preferred. 

This method is slow because of the multiple operations on a shuttle machine. The heat of extmsion sterilizes the bottle, which is not readily achieved after molding. Blow-mold/fill/seal systems are used commercially for beverages and for pharmaceutical packaging. 

Blow-fill technology is an aseptic process whereby the container is formed from thermoplastic granules, filled with sterile solution and sealed, all within one automatic operation. The bulk solution should have a low bioburden and is delivered to the machine through a filling system that has been previously sanitized and steam sterilized in situ. Concern has been expressed that the machine itself may generate particles. The plastic granules are composed usually of polyethylene, polypropylene or one of their copolymers and are heat extruded at 200°C into a tube. The two halves of a mould close around this tube and seal the base. The required quantity of sterile fluid is filled into the container, which is then sealed. Products packed in this way include intravenous solutions, and small volume parenteral, ophthalmic and nebulizer solutions. The... 

There are several machine systems available for aseptically filling glass and plastic bottles for still juices. (Aseptic filling of drink cartons is covered in Section 9.7.) Carbonated drinks are not aseptically filled. There are two main aseptic filling workflows, with a third workflow used less frequently. The first system sterilises the container, fills and seals it the second takes a sealed, precleaned bottle, removes the seal in a sterile environment, fills and re-seals the container. The third system blows a bottle and while it is still sterile fills it and then seals it, all within the same machine, this is known as a form-fill-seaF (FFS) system. 

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