How To Incorporate Blow Fill Seal and Form Fill Seal Technology
Blow-Fill-Seal (BFS) technology is a manufacturing technique used to produce small, (0.1mL) and large volume, (>500mL) liquid-filled containers. Originally developed in Europe in the 1930s, it was introduced in the United States in the 1960s, but over the last 20 years it has become more prevalent within the pharmaceutical industry and is now widely considered to be the superior form of aseptic processing by various medicine regulatory agencies including the U.S. Food and Drug Administration (FDA) in the packaging of pharmaceutical and healthcare products.
The system has been employed in production of ophthalmic and respiratory therapy products for some time, and lately BFS technology has been gaining increasing acceptance in the parenteral drug marketplace, replacing traditional glass vials for a number of applications.
In BFS technology, a container is moulded from plastic, aseptically filled with liquid dosage form and hermetically sealed in one continuous, integrated and automatic operation, without human manipulation. By contrast, traditional aseptic processing allows a final sterile drug product to be achieved by individually sterilizing the containers, materials and equipment used in the process, resulting in a unified sterilized product. In traditional aseptic processing, containers are either supplied clean and sterilized to the filling line, or they are cleaned and sterilized within the aseptic filling line. Plastic containers, for example, are usually washed, dried, sterilized and cooled before filling. Traditional aseptic sterilization involves handling and manipulation of the material, containers and sterilization filling processes with human intervention, and therefore carries a high risk for contamination during processing. One of the most difficult issues to deal with is airborne contamination. The risk of this occurring is directly related to the number of people working in a clean-room and the level of congregation by personnel in areas where critical aseptic manipulations are carried out. Ordinary walking by a person can emit roughly 10,000 skin particles per minute, each of which has the potential of harbouring microbial contamination. Advance BFS technology overcomes the risk of airborne contamination by carrying out the process within a sterilized area in which there is no human presence.
The essential steps of modern BFS technology are:
1. Granules of a thermoplastic polymer (e.g. polypropylene, polyethylene, co-polymers or other blow-mouldable resins) are pneumatically conveyed from a non-classified area to the hopper of the BFS machine.
2. The plastic is fed into a multi-zone rotating screw extruder which produces a sterile homogenous polymer melt (typically by heating to 160-200 °C).
3. Melted polymer then flows to a parison head which produces a hollow tubular form of the hot plastic (called a parison). The parisons are prevented from collapsing by a stream of sterile filtered support air (hence the term blow-feed).
4. The bottom of the parison is pinched closed, while the tope is held open in a molten state.
5. Filling needles (called mandrels) deposit the required volume of liquid in the container.
6. The mandrels are withdrawn and the upper part of the mould closes to seal the upper part of the container.
7. The mould is opened and the completed filled containers are conveyed out of the BFS machine and sterile area to a remote station where excess plastic is removed and the finished product is sent for labelling and packaging.
Form-fill-seal is a term used for more general technology employed in a wide variety of industries for packaging products, e.g. baked goods, dairy, coffee, confectionary, meat, frozen foods and spices. For these applications the package may be a bag that is formed from a continuously supplied plastic tube that is heat sealed once the required product has been deposited within the bag. Form-fill-seal is a technology can also be applied to pharmaceutical products with the same goal as BFS, i.e., to reduce contamination by ensuring that the environment where production, filling and sealing of containers are done with minimal human intervention in a closed and sterile machine. Both technologies provide increase production using low operational cost while at the same time increasing the quality of the product compared with traditional aseptic processing.
In using the BFS and FFS technology for pharmaceutical liquid dosage forms, it is important that the machines are surrounded by class 1M environment, or better. The container formation, filling and the sealing must be conducted in a class 100 area. Before commercial production is begun, the system must be validated by a media fill run.
One container made during BFS and FFS systems can take approximately 10 to 15 seconds of production time, and the fill time is generally fast. The number of dosage forms, i.e., total volume that the company can make depends on the number of the moulds that the machine is equipped with. The larger the machine, the higher the throughput. Labelling is generally performed outside the machine in a non-sterile area.