The increasing demand for parenteral products delivered in vials brings with in an increased demand for sterile vial filling — can closed-vial technology help manufacturers keep up?
By the year 2021, the global market share for pharmaceutical products housed in vials and ampoules is expected to reach $12.4 billion, thanks in part to increased demand for products such as biopharmaceuticals, vaccines, and insulin. This demand will increase all over the world, especially in emerging markets in Asia, which is already a nearly $3 billion market, expected to reach over $4 billion by 2021.
Vials have overtaken ampoules as the delivery method of choice for many parenteral products due to a lower risk of breakage and contamination. As the demand for these products continues to grow there is a commensurately increased need for sterile vial filling that can keep up with escalating demand.
In spite of continuous improvements in technology and best practices, sterile or aseptic vial filling remains one of the most complex and expensive processes handled by drug manufacturers and CMOs today. Closed-vial technology is one advance which may simplify sterile vial filling, but it has both advantages and drawbacks for those in the pharmaceutical industry.
The risks associated with contamination during sterile vial filling are real, even as advances have helped to drastically reduce contaminations rates.
Every year, patients are exposed to contaminated parenteral products, with a mortality rate as high as 15%. While advances in aseptic filling technology and practices have helped to drastically reduce the rate of contamination, the fact is that the risk remains real and ever-present.
Many contaminations occur in hospitals and pharmacies as a result of user error, but around 20% of contaminations in parenteral products occur as a result of the manufacturing process, including mistakes in aseptic filling. Because of the very real and present danger associated with contaminated parenteral products, sterile filling requires a complex and time-consuming quality control process to ensure product efficacy and patient safety.
Advances in technology have helped to reduce the rate of contamination and protect both patients and manufacturers. Isolators, process analysis technology, and improvements in personnel gowning procedures have all improved the aseptic filling process. These advances also slow the process down, however, and as demand grows, the need to quickly — and safely — address sterile filling requirements becomes more and more pressing.
Closed-vial technology offers one solution to sterile vial filling that allows pharmaceutical manufacturers and CMOs to meet increasing demand without sacrificing quality or safety.
Closed vials are molded in an ISO5 cleanroom. Vials consist of the vial itself, a stopper made of a heat-sensitive material, rings, and a polyethylene cap. Once the vial has been assembled, it is sterilized, preferably by gamma irradiation. Because the vial stopper is heat-sensitive, autoclaves and other heat-based sterilization procedures cannot be used for closed vials.
To fill the vial, a needle is inserted through the stopper to deliver the drug product. The puncture trace is then filled in using a laser. Closed vials arrive ready-to-fill, and can be loaded in a variety of ways, including beta-bags or vaporized hydrogen peroxide airlocks. Regardless of how the vials are loaded, the sterile, ready-to-fill vials cut down on component preparation time and cleanroom space.
Closed vials can be used for lyophilized products, but special equipment is needed to handle filling, and the primary drying phase is longer than for traditional glass vials. Tests suggest, however, that closed-vial lyophilization may produce a more stable product.
Closed-vial technology offers numerous benefits to manufacturers during the sterile vial filling process and to end users.
By using a closed vial, the opportunities for contamination are reduced, and aseptic filling can be handled more quickly without added risk. Besides reducing time for component preparation and streamlining the aseptic filling process, closed-vial technology also offers other advantages to drug manufacturers and CMOs engaged in sterile vial filling.
- Reduced risk of contamination – Closed vials are closed from the moment of their manufacture and remain closed by design. The only time that a closed vial runs the risk of contamination if handled properly is during the brief period of needle penetration. By contrast, traditional glass vials may stay unstoppered for as much as 30 minutes, substantially increasing the opportunity for contamination.
- A smoother supply chain – Because component prep time is reduced, the risks and challenges that come with component preparation are removed as well. Closed vials arrive already sterile and ready-to-fill, eliminating the need for water for injection washing, sterilization, and hot-air depyrogenation. This means filling can be done faster, without sacrificing quality.
- Easier handling – While instances of patients becoming exposed to contaminated parenteral products is relatively rare, in the vast majority of cases where such contamination does occur, it is due to handling in hospital pharmacies or by healthcare providers. By capping the closed vials with easy-to-open polyethylene caps and stoppers with large piercing areas, closed vials make handling easier and reduce the risk of contamination by hospital staff.
Closed-vial technology is one extremely useful tool to help meet the increasing demand for sterile vial filling, but it has limitations.
At the end of the day, closed-vial technology is another huge leap forward in the realm of sterile vial filling, but it doesn’t solve every problem, and it isn’t the right fit for every drug manufacturer or every CMO. Closed-vial filling requires certain changes to workflow and supply chains that not every CMO can accommodate.
Closed vials must be held still during piercing and laser sealing, and manufacturers may have to invest in new equipment to take advantage of closed-vial filling. Closed-vial filling also requires different validation than sterile filling using traditional glass vials.
While the use of closed vials can provide a safer and faster solution for sterile vial filling, it isn’t right for every situation. Manufacturers should take every relevant factor into account when deciding on how best to prepare their product in a way that ensures efficacy, quality, and patient safety.