Aseptic Blow-Fill-Seal Technology vs. Traditional Aseptic Processing

 
The BFS critical processing zone is continually supplied with HEPA-filtered air by an air shower device (shroud).  The BFS critical zone is the area where the containers are exposed during filling. Air in the critical zone meets Class 100 (ISO 5) microbiological standards during operations. The critical zone is continuously monitored to ensure a positive differential pressure is maintained between the shroud and the adjacent cleanroom.
 
Plastic vs. Glass Containers

Injectables, ophthalmics, biologicals and vaccines are produced in a number of different types of containers, including bottles, vials and ampoules that are made from glass and plastic. Protecting the contents of these aseptic liquid drugs through filling, packaging and transportation, and allowing for safe and easy administration are critical objectives in the aseptic process. The industry is infused with a strong quality control emphasis. Raw materials, and in-process and finished products are continually checked for approval and rejection.  
 
The packaging needs for pharmaceutical liquids are quite demanding. It is not unusual for degradation of the product to occur during processing or while in transit. The physical properties of liquids can be altered with inadequate packaging components. For aseptic filling, the package must be produced, stored, filled and sealed under conditions that preserve sterility. Likewise, the appearance of particulates in sterile solutions is equally undesirable.
 
Glass, although a standard in the aseptic pharmaceutical liquids industry, is not without its limitations. There is the safety issue – glass vials are subject to breakage, both in transit and while being administered.  Handling glass containers always involves a certain amount of risk of lacerations and glass splinters. Glass ampoules, for example, generate a fine array of small glass particles during opening.  
 
Manufacturers using glass containers are also subjected to design limitations when the designs become somewhat complex. With glass containers, as design complexity increases so does the cost. Once glass containers are produced, they need to be transported to the aseptic facility. Glass is typically transported in cardboard boxes that can contain mold spores, such as Penicillin sp. and Aspergillus sp., as well as bacteria like Bacillus sp.  Paper, also used in the shipping of glass, can also contain mold spores. The rubber closures used on the glass containers can have mold contamination.
 
Domestic drug companies have been slow to change to plastic, primarily due to the existing installed base of glass production of small-volume parenteral drugs in the United States. However, the same is not the case with new drugs that are coming onto the market. These are more frequently being looked at, and submitted for FDA approval, in plastic containers produced by advanced BFS aseptic processing. Supporting this move is that the BFS processing resins, polyethylene and polypropylene, are generally considered inert by the FDA. Many of the blow molding resins used in BFS processing have received international acceptance as suitable for food and drug applications, and many of the drug products produced outside of the United States can be found packaged with these resins.
 
With the continued refinement of BSF technology, its acknowledgment by the FDA as a preferred technology for aseptic processing, and its growing acceptance by drug companies, the migration from glass to plastic containers used for aseptic pharmaceutical liquids is growing rapidly. It has become more cost effective to use plastic containers for aseptic liquids, which effectively costs manufacturers one-third of the cost of glass. Plastic is less expensive to ship because the containers are lighter. For small-volume parenterals, the use of plastic is inevitable, and increasingly being considered for these reasons.
 
Although many BFS systems make available only a limited number of container choices within each container category, some BFS machines do allow for broad versatility in container design. Advanced BFS machines can design virtually any container mold through the use of sophisticated CAD/CAM technology and 3-D modeling. These design systems, when interfaced with the latest in CNC and EDM machinery, ensure fabrication of key components to precise tolerances.  

BFS machine designs also allow for mounting of separate sterile items (inserts) within the BFS container, and in-mold coding and engraving, which provide further opportunities for innovative design over that of glass products.
 
Flexibility with Changeovers Allows Shorter Runs, Increased Uptime, Maximized Throughput

Modern BFS system design is focused on simplicity and flexibility. Many BFS machines are configured to produce more than one bottle shape or format. This makes it easy to change over from one container size to another. A BFS machine might produce a family of 2, 3 and 5ml, then switch to a family of 5, 10 and 15ml, or to one of 10, 15 and 20ml, moving from one to the other with relative ease of machine set-up. This is ideal for manufacturers performing contract packaging of aseptic liquid pharmaceutical solutions, because of their need for changeover flexibility.
 
The growing usage of biologics is demanding packaging in different formats. They usually require smaller process runs and are typically heat sensitive.  Many of these new biotechnological drugs do not withstand steam sterilization or irradiation and so are best treated aseptically. More advanced BFS machines have been designed so they can handle these heat sensitive products.
 
Machine models are available that can produce containers ranging in size from 0.1mL to 1000mL at production rates of 15,000 units per hour, depending on container configuration. BFS machine efficiency is very high.  More advanced BFS machines can approach 99 percent uptime efficiency, which is significantly higher than traditional aseptic processing which is plagued with slow-downs in part because of manual interventions. To further minimize potentials of system downtime, some manufacturers are now segmenting their high-volume process lines into more short-run lines, in the event that if one of the lines goes down for maintenance or repair, it will not stop the entire production throughput.
 
When aseptic throughput is interrupted, or not running because of downtime, the entire process line is affected, which represents a significant production loss to the manufacturer.  
 
An Aseptic Technology Destined to Prevail

More rapid container closure processing, elimination of aseptic critical-area personnel interventions, increased system uptime over traditional processing, pyrogen-free molding of containers and ampoules, more flexibility with container design, and an increased capability to capitalize on short runs - these are some of the benefits for manufacturers inherent in advanced blow-fill-seal aseptic technology. And for the consumer, increased safety and confidence in their drug products are strong additional benefits.
 
These are advances that are significant, if not fully realized yet within the aseptic liquid pharmaceutical marketplace. But it is apparent that advanced BFS aseptic technology is destined to become a major player in this arena.