For many years, most parenteral drug products have been packaged in borosilicate glass. Why has glass remained the standard for so long and why would the pharmaceutical industry be interested in exploring other packaging options?
Early packaging of pharmaceuticals was based on the availability of mass-produced containers of the day. Glass was the best choice at that time for many non-parenteral drugs. Borosilicate glass became a better option over ordinary soda-lime glass due to its higher hydrolytic resistance and thermal shock resistance. These unique properties enabled parenteral and freeze-dried drug products to be packaged in borosilicate glass.
Over the years, polymers have become widely available, however, existing polymers alone do not adequately address all pharmaceutical packaging requirements. During that same period, drug product and vaccine formulations became more complex, requiring packaging with increased flexibility and durability. Even with the introduction of formulation additives to mitigate potential adverse effects of glass and stabilize the drug molecule in the formulation, eventually the needs of complex biologic drugs, vaccines and therapies have outpaced the performance capability of glass. For example, the cold storage requirements, pH extremes, reduced particulate counts and protein aggregation concerns along with other stringent demands have motivated pharmaceutical developers to search for better packaging options. These long-standing packaging issues have been managed, but resulted in product recalls, drug shortages and immunogenic harm to patients.
With the development of advanced drug formulations, has the use of plastic or polymer containers been explored to address some of the issues encountered? If so, why hasn’t this alternative become a new standard for pharmaceutical packaging?
While there are advantages to the use of plastic containers, there are some definite limitations that have slowed full conversion to this type of container. Compounds originating from the polymer can leach out and migrate into the drug product. Chemicals in adhesives used to adhere labels can migrate through the polymer. Obviously, these are major concerns for safety and efficacy reasons; greatly limiting the length of time drug products can safely be stored in the container. Furthermore, plastics are breathable materials with poor gas barrier properties. This is a major problem for drugs that are sensitive to oxidation from oxygen in the air and radiation sterilization technology. Some biologic formulations require a stable reduced or non-aerobic environment to prolong the shelf-life. Even some plastic manufacturers warn against using sterilization technologies such as e-beam and gamma because it can lead to reactive oxidant species in the plastic that can migrate and oxidize the drug product.
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In particular then, can you tell us what sort of technologies address the current unmet needs of biologic drugs and vaccines while offering a safe and tested solution?
Over the last decade material scientists have developed a robust alternative to ordinary glass and plastic containers that addresses the shortcomings of both materials. SiO2 Materials Science has developed a technology that coats the inside of plastic containers with an ultrathin glass-like barrier layer that eliminates the major concerns of glass and plastic when these materials are used alone. SiO2 coated containers have been exhaustively tested and found to be superior to glass and plastic containers. Multiple drug stability tests have been completed and many more are underway. In fact, the FDA is familiar with the technology and is working with SiO2 in establishing a regulatory pathway for our customers to use as a glass substitute. This is because these hybrid containers not only pass all the compliance, biocompatibility and toxicity requirements, but show significantly lower leachables, particles and resistance to hydrolytic attack compared to glass. This is just an overall better product.
There are other primary container options on the market such as Schott Type I Plus, which is a pure glass coating on borosilicate glass that eliminates ion migration. Why has this option not become more mainstream in the marketplace?
Because it only addresses a niche need in the marketplace. For drugs that have sensitivity to metal ions due to chelation, such as zoledronic acid… this could be a good option. However, it does not solve all the other problems that are omnipresent with glass. Borosilicate glass containers are prone to chipping and breakage and are far more dimensionally variable than plastic containers, which can compromise sealing integrity. These shortcomings are not overcome by incorporating a coating layer on glass containers. SiO2’s hybrid containers combine the best features of glass and the best features of plastic with none of the shortcomings. In addition, the coating applied to the inside surface of the container is engineered to be chemically consistent and uniform. The coating can be optimized for the specific drugs to ensure drug stability over the shelf life.
There are new and improved glass options on the market that claim to improve breakage and chemical resistance that leads to delamination. What is the future for this glass?
Again, it addresses a segment of the market, but is still burdened with inherent issues. Despite improvements in the strength of glass to reduce the occurrence of breakage, as with chemically strengthened aluminosilicate glass or Valor glass, …it can still break. Look no further than the protective gorilla glass on everyone’s mobile phone. This is in principle the same material…it breaks!
What makes SiO2 technology so attractive to the US government that they have invested $143 million in their primary containers for the eventual launch of COVID-19 vaccine?
Besides the performance advantages of SiO2 technology, there are a few key things that differentiates SiO2. The most obvious is securing a US source of primary containers since most of the supply is overseas. SiO2 manufacturing is based in Auburn, Alabama. Second, there has been ongoing concerns of a glass shortage due to the vacuum of demand from COVID-19 vaccine developers and the existing biologic drug market that continues to grow. The glass-like material that’s inside each SiO2 container is derived from raw materials that have no ties to the glass supply chain. Its more closely related to raw materials used in the manufacture of microelectronic devices and silicone polymers. Lastly, the ability to scale-up SiO2 technology is unmatched compared to traditional glass manufacturing. In a very short time, 80 million units of vial manufacturing capacity is already on-line in Auburn, Alabama and another 50 million coming on-line in December. It only takes 3 to 4 months to add that capacity due to the inherent flexibility and design of their manufacturing unit operations.