The aseptic blow–fill–seal (BFS) process blow-molds unit- or multidose containers, fills sterile product, and hermetically seals the package in one highly automated machine. Because the BFS process eliminates human interventions in the filling environment, the biggest source of contamination, makers of ophthalmic, inhalation, and parenteral products such as biologics and vaccines find BFS technology appealing.
In fact, the US Pharmacopeia considers aseptic BFS to be an advanced aseptic process (1). "Aseptic BFS systems offer a unique combination of flexibility in packaging design, low operating cost, and a high degree of sterility assurance," explains Chuck Reed, director of sales and marketing at Weiler Engineering, (Elgin, IL), in a white paper titled "Advances in Aseptic Blow–Fill–Seal Processing of Pharmaceutical Liquids Improve Product Integrity and Patient Safety."
The blow-molding process itself helps achieve high sterility-assurance levels because it produces a container that is free of viable micro-organisms and endotoxins. Reed's white paper cites a study that shows fractional spore-contamination levels of less than 1 × 10–6 and a three-log reduction in endotoxins. The probability that the blow-molding process will create a nonsterile unit is roughly 1 in 1,000,000 (2).
The BFS process consists of the following five completely automated steps (3–4):
- Step 1: Thermoplastic resin such as high-density polyethylene or polypropylene is melted and extruded into a tubular shape or parison.
- Step 2: When the parison reaches the proper length, the mold closes and the parison is cut. The bottom is pinched shut, the top is held in place, and the mold is positioned under the blowing and filling nozzle.
- Step 3: The blow–fill nozzle descends into the mold and expands the parison with a jet of sterile compressed air or vacuum. Once the container is formed against the mold, the nozzle precisely fills sterile product into the container.
- Step 4: Separate sealing molds close to form the top and hermetically seal the container.
- Step 5: The mold opens and the sealed container exits the machine for inspection, labeling, and cartoning.