The Relevance of Primary Packaging in Maintaining Drug Stability
From the moment pharma companies formulate a drug to when a doctor injects it into a patient, the primary packaging (the packaging that is in direct contact with the drug) plays a crucial role in preserving and protecting that drug.
Drug stability is a drug’s capacity to maintain the chemical, physical, microbiological, therapeutic, and toxicological properties it possessed at the time of its manufacture throughout storage and usage.1 Pharmaceutical companies typically perform stability testing throughout the entire drug development process. The primary packaging of a drug can significantly affect its stability over the shelf life of the drug. As the government’s Operation Warp Speed (OWS) races to get COVID-19 vaccines to the 328.2 million people of the United States, pharma companies are scrambling to ensure that they have sufficient primary packaging options that are effective and safe. The OWS goal is to produce and deliver 300 million doses of safe and effective vaccines with the initial doses available by January 2021.
Essential Qualities of Primary Packaging for Pharma Drugs
Ideally, primary packaging should have an impenetrable and inert barrier that blocks anything from migrating into a drug formulation. It should also eliminate interactions that can pull out the active pharmaceutical ingredients of a drug or its excipients. A package that will not break or leak and one that can protect the product from adverse external influences like light, moisture, oxygen, biological contamination, and mechanical damage over its lifetime would also be ideal.
Vaccines, like most injectable drugs, are typically packaged in sterile glass. Borosilicate glass is the most popular primary packaging material for injectable drugs. Glass is chemically inert and its visual clarity makes it an excellent choice for inspecting products. Plastics are also used for primary packaging, albeit less commonly, because of their flexibility, low-weight, and cost-effectiveness.
Both borosilicate glass and plastic have their merits to satisfy some of the previously mentioned requirements for primary packaging. However, both materials do not fulfill all requirements.
SiO2 Introduces a New Hybrid Primary Packaging Solution for COVID-19 Vaccines
SiO2 has leveraged the principles of materials science and engineering to develop a new hybrid primary container that blends the advantages of glass and plastic materials without their respective deficiencies. We believe that vials and pre-filled syringes constructed from this hybrid material are the closest things to an ideal primary container on the market today.
The surface of the hybrid SiO2 containers is composed of a material that maintains drug stability adequately – it is shatter-resistant, optically clear, low-weight, and chemically durable. This technological advancement is based on the synergy between high-precision injection-molded plastics and plasma coating technology. The container itself is molded out of a medical-grade, engineered cyclic olefin polymer (COP), a type of plastic that is resistant to breakage and durable over a wide range of temperatures (-80 to 121 °C). COP serves as the foundation for depositing a proprietary glass-like barrier coating system as shown in Figure 1
Each layer of the barrier coating system is deposited sequentially by a process known as plasma-enhanced chemical vapor deposition (PECVD). This process, which originated from the microelectronics industry,3,4 can deposit inorganic and organic nanomaterials with physical and surface characteristics that have been unachievable with conventional polymers. We engineered the layered architecture to block the migration of contaminants originating from the container or the environment entering the drug formulation.
Furthermore, the dense and inert glass-like chemical composition of the drug contact surface eliminates any metal ion leachables and resists hydrolytic attack, which is unachievable by any glass material.5 The entire barrier system adheres to the polymer backbone through strong covalent chemical bonds that remain intact after extremes of chemical, thermal, and mechanical stress.
Quality Control: Testing the Integrity of Si02 Vials
Extensive testing was conducted to demonstrate the performance integrity of the barrier coating system. SiO2 vials passed hydrolytic resistance and surface durability (i.e., delamination) tests according to USP <660> and USP <1660> guidelines, respectively.
We developed an internal set of rigorous tests that demonstrated hydrolytic and delamination resistance to formulations ranging in pH from 3 to 14 at elevated temperatures. SiO2’s testing was purposely designed to exceed the conditions of both USP <660> and USP <1660> to demonstrate the robustness of the barrier coating system.
Results of comprehensive extractables and leachables (E&L) testing on SiO2 vials revealed that the drug contact surface was ultra-clean without any compounds originating from the underlying polymer. Any detectable compounds were at trace levels or well below the established analytical evaluation thresholds.5,6
A full battery of compliance testing was completed on SiO2 containers to support drug product submissions. The compliance testing included compendial (i.e., EP, USP, JP), biocompatibility (i.e. ISO 10993), and toxicity (ICH-Q3D). This information is included in SiO2’s drug master file submission to the FDA.
Lastly, the barrier to gases such as oxygen and ethylene oxide (i.e. for terminal sterilization) is taken for granted in glass since it is an impenetrable material to gases. Most plastics, however, are breathable materials with measurable but varying permeation to gases that can compromise drug stability. Drugs that are sensitive to oxidation can degrade more rapidly in ordinary plastic containers, which can significantly reduce shelf-life. The pure silicon oxide layer has the highest density of any layer in the barrier coating system stack, which is an important requirement to block gas permeation. In fact, the oxygen barrier performance of the coating is maintained after 1000 lb of compression force is applied to coated vials.7
When it comes to preserving drug stability, the choice of primary packaging plays a crucial role. The primary packaging can either extend or cut short the shelf life of a drug.
Pharma companies are working overtime to develop safe and effective vaccines according to a mandate by the US government’s OWS. Not only are we experiencing a global shortage of potential COVID-19 vials, but when these vials become available, we need them to satisfy all the requirements for primary packaging. SiO2’s hybrid packaging advanced technology is a contender to previous packaging models and can potentially save millions of lives.
Let SiO2’s Smart Vials help bring your new innovations to life and keep your patients safer.
- Wong AW, Datla A. 13 – Assay and Stability Testing. In: Ahuja S, Dong MW, eds. Separation Science and Technology. Vol 6. Academic Press; 2005:335-358. doi:10.1016/S0149-6395(05)80057-1
- Guidelines on Packaging for Pharmaceutical Products. Accessed November 10, 2020. https://www.who.int/medicines/areas/quality_safety/quality_assurance/GuidelinesPackagingPharmaceuticalProductsTRS902Annex9.pdf
- Hamedani Y, Macha P, Bunning TJ, Naik RR, Vasudev MC. Plasma-Enhanced Chemical Vapor Deposition: Where We Are and the Outlook for the Future. InTech; 2016.
- Jones SW. Introduction to Integrated Circuit Technology. Published online 2001:21.
- Weikart CM, Pantano CG, Shallenberger JR. Performance Stability of Silicone Oxide–Coated Plastic Parenteral Vials. PDA J Pharm Sci Technol. 2017;71(4):317-327.
- Weikart C, Saaler-Reinhardt S. Glass Like Inner Barrier Coating Prevents Contamination of Drug Products with Potential Impurities From Primary Containers Composed of COP, A Case Study. Published online 2016.
- Weikart CM, Breeland AP, Wills MS, Baltazar-Lopez ME. Hybrid Blood Collection Tubes: Combining the Best Attributes of Glass and Plastic for Safety and Shelf life. Slas Technol. 2020;25(5):484-493. doi:10.1177/2472630320915842