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COVID-19

Partnership vs. Salesmanship — Bringing Choice to Pharma Packaging

They grow stale. The needs of customers go unmet as incumbents feel content to provide only small iterations, confident in their knowledge that they own the market outright.

Innovation thrives on competition. Businesses need to feel the pressure of disruption at their backs to pursue new ideas and meet the evolving needs of their customers. Industries with little competition invariably innovate less than industries where competition is rampant.

The tech boom of the last 20 years delivered a wake-up call to many industries that had previously considered themselves safe. By now, most markets have shifted to favor the innovators, but a few have fallen through the cracks. For one such industry, pharmaceuticals packaging, that’s about to change.

Glass pharma packaging today is led by Schott, a company founded in 1884 by a man of the same name who invented the borosilicate glass that nearly all pharma companies still use today. While the longevity of his product is a testament to his genius, the world has gone nearly 140 years with almost no improvements to a product that desperately needs them.

Anyone who has worked in pharma or medicine long can talk at length about the problems of traditional glass products. They break easily, and even when they don’t break, they can cause delamination, a defect in which containers contaminate the medicines within them with potentially serious consequences. Incremental improvements have attempted to pacify buyers of pharma glass, but the world needs something better — especially with the COVID-19 vaccine approaching quickly.

Unfortunately, the same industry giants who have settled for incremental progress have decided not to hurry in the face of new pressures. The chairman of Schott recently spoke to the media on his commitment to reserve his glass supplies for the eventual winner of the COVID-19 vaccine race. That may be the safe choice, but while Schott keeps its supplies in reserve, smaller pharma and biotech companies are left out in the cold.

This pandemic should have inspired existing industry players to take action and innovate. Instead, they have responded with the same outdated thinking that has held back pharma glass for more than a century. It’s time to do better.

Breaking down an outdated process

Big glass manufacturers do not partner with their customers. They are simply order-takers. Customers get one option, and the companies fulfill that option. If they don’t like it, they have nowhere else to go.

Customers of established pharma glass companies report a humdrum sales process. The salesperson visits, makes small talk, asks how much they want, and places the order. Bigger customers might receive the occasional dinner invitation. No one feels like a partner. No one gets to voice complaints about unmet needs. The world spins as slowly as it always has.

What existing players in this industry have forgotten is that pharma glass is not a commodity. Far from it, pharma packaging plays host to a wealth of opportunities for anyone creative or bold enough to try something new. With so many customers unhappily settling for what they have always had, the advent of something better promises to shake the foundations of the pharma community.

Bringing true partnerships to pharma

Customers of companies like Schott (and the patients who deal with their products) have waited long enough. Finally, new contenders have risen to the challenge, invigorated by the demand generated by the COVID-19 pandemic and funded by hundreds of millions of dollars in investments.

These new pharma packaging companies don’t present a “take it or leave it” attitude. On the contrary, they want to know what their customers don’t like about existing products. They want to hear about problems with delamination, breakage rates, compromised samples, and all the other issues that have plagued the industry for so long. They want patients to receive the care they deserve, and they are ready to meet those needs with new products.

The new disruptors in pharma glass employ bright people in every part of pharmaceuticals from manufacturing to research and development. These contenders recognize that they face a market that has stagnated, and they want to bring something better to the table. Where the old guard focuses on maintaining sales numbers for outdated products, the new generation follows a patient- and customer-first approach.

That should scare the people who have sat comfortably at the top of pharma glass for far too long. The world is changing. Disruption has reached a new corner, and with the wheels in motion, the changes will not slow down until the industry has turned into something that hardly resembles its former self. Pharma glass has reached its moment, and by the time the COVID-19 vaccine finally enters production, the new market entrants will have staked their claims.

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COVID-19

Understanding the Glass Shortage in Pharma

Imagine someone announces a vaccine for COVID-19 tomorrow. People throw parades — at respectable social distances, of course. Politicians speak about the resilience of the population and the end of a global nightmare. Restaurants and gyms get ready to welcome back the masses, schools send out emails to prepare for fall classes, and then…everyone has to take it all back.

Why? Because the pharma system isn’t even close to ready to distribute vaccines on a large scale.

Dr. Rick Bright, former head of the U.S. Biomedical Advanced Research and Development Authority (BARDA), was recently fired from his position for what he says were political reasons. Among other issues Bright raised that may have angered others within the government, he claimed that manufacturers of traditional borosilicate glass had already exhausted their supplies in May. Further, he projected that it could take two years to produce enough new glass to meet U.S. vaccine needs, to say nothing of the rest of the world.

Others, including Bill Gates, have warned of the same problem. Even if researchers manage to discover an effective treatment for the virus outright, the current system relies on the production of glass vials, and the current producers are woefully unequipped to meet demand. Despite public projections of confidence, the behind-the-scenes truth is one of bare shelves and limited operating capacity.

Don’t listen to the executives of “big glass” and their reassurances that all is well. Medical researchers and smaller pharma companies asking for glass can’t get it. Industry experts all agree that the world doesn’t have enough of the glass necessary for vaccines. Those who stand to profit can mislead all they want, but they can’t produce more glass from thin air.

An Old Story of a Controlled Supply

The biggest players in pharma glass have owned the industry for a long time. Schott, the biggest company in this space, is more than 100 years old and named after the man who first invented borosilicate glass, which vaccines still use today.

The chairman of Schott has made the media rounds recently to reassure the world that the glass shortage does not exist. Meanwhile, smaller pharma companies have claimed that Schott continues to reject their orders. When the biggest supplier controls the overwhelming majority of the supply, smaller outfits have no power to innovate or push back.

This sales-first, patient-second attitude of reserving glass containers for the eventual “winners” of the COVID-19 vaccine race puts lives and livelihoods at risk. Why should one roadblock determine who gets to help the world and who must sit on the sidelines? The time has come for change in the pharma glass industry.

Coronavirus Fears Caused the Glass Shortage

The pharmaceutical glass packaging industry is a $15 billion market all on its own. How did things get so dire, so quickly?

Fears regarding the spread of COVID-19 drove BARDA and the federal government to invest hundreds of millions of dollars in glass alternatives. Federal institutions recognized that the looming need for a vaccine necessitated a boost in manufacturing, but existing players still don’t have the capacity to meet that demand. And that doesn’t just hurt COVID patients.

Millions of people receive vaccines every day. They need and deserve safe equipment just as much as people suffering from the novel coronavirus deserve the same. Because of the uncertainty around the future, though, people who need vaccines for non-COVID medical reasons will find supplies scarce. If the industry can somehow meet the needs of COVID patients in the short term, it will come at the cost of everyone else.

Finding an Alternative

Glass doesn’t have to hold up the whole operation. Instead of pouring everything into more glass and depending on the existing monopoly to pull through, pharma should rethink the entire idea of glass and look to newer, more innovative companies to rise to the occasion.

Pharma glass has seen only small, incremental changes over the last 100 years. Improvements in processes have made it easier to produce borosilicate products, but the products (and their problems) remain largely the same.

The world needs a better answer to glass, and it needs that answer soon. A vaccine for COVID-19 will arrive, and when it does, the world will need an established distribution network to return to something that resembles normality. As new technologies have revolutionized industries and sub-industries for the last two decades, the time has come for pharma glass to experience the same disruption. Slow, outdated industry giants must make way for new companies with new visions for the future of pharma glass. Only by tackling the very idea of glass can the global pharma industry meet the needs of a post-COVID population.

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COVID-19

The Compatibility of SiO2 Smart Vials with Fill Finish Manufacturing Lines

Understanding the Fill Finish Process

The value of the fill-finish manufacturing market is estimated to reach $5.15 billion by 2024, according to a report published by Zion Market Research. Pharmaceutical and biotechnological companies dominated the fill-finish market in 2017.

Drug products that are delivered to individuals via the parenteral, ophthalmic, or inhaled routes typically bypass the body’s immune system. The US Food and Drug Administration (FDA) requires that Pharma companies package these types of drug products using a sterile method for the safety of consumers. However, the fill-finish step has proven to be a major rate-limiting step in the process of delivering vaccines, according to a report to the president on reengineering the influenza vaccine.

The fill-finish process is a significant step in the drug manufacturing process. When manufacturing injectable vaccines, there is no method for sterilizing the vaccine when it has been packaged in its final container. This is why the vaccine needs to be filled in an sterile environment, also known as an aseptic fill-finish. During this step, the sterile drug is transferred from a filling needle to a sterile container such as a vial or syringe. Any marginal error in this process can lead to quality failure and can cause harm to recipients of the vaccine. Aseptic processing is challenging due to the need for specialized equipment and skilled personnel. The FDA only recommends this step for formulations where terminal sterilization is not possible.

In 2013, the United States Biomedical Advanced Research and Development Authority (BARDA) recognized the need for Pharma companies to expand their manufacturing facilities, including their fill-finish capacity. BARDA awarded contracts to four companies to make up its “fill and finish manufacturing network.

In 2020, BARDA is yet again funding several pharma companies to help expand their fill-finish capacity for the speedy manufacturing and delivery of COVID-19 vaccines globally.

Re-Evaluating Fill Finish Manufacturing Lines and Processes for SiO2 Hybrid Vials

Although we have designed SiO2 vials and syringes to meet the International Organization for Standardization (ISO) standards, we still needed to re-evaluate their compatibility with fill-finish manufacturing lines since the conventional fill-finish equipment was initially designed with glass in mind.

To ensure smooth fill-finish operations with a new primary vial and syringe, the properties of the packaging material need to be cross-examined, including the weight, surface finish, defect inspection, propensity for static charge, and particle loads.

Weight
SiO2 has conducted extensive trials with machine-filling manufacturers to ensure the compatibility of our SiO2 hybrid vials. Although the weight of an SiO2 vial is approximately two-thirds of a similar-sized glass vial, we shifted the center of mass of the SiO2 vial down to reduce the risk of tipping over.

Surface Finish
According to the results from our fill-finish trials, the cyclic olefin polymer surface finish of SiO2 vials does not impede them from running smoothly on the fill-finish line.

Defect Inspection
We observed that the inspection systems for defects on SiO2 vials require some recalibration since what may be perceived as a serious defect in glass is only cosmetic in SiO2 vials.

Static Change and Particle Loads
The SiO2 cleanroom environment is controlled for contamination and other environmental factors such as temperature, humidity, and pressure. We manufacture SiO2 vials in this environment with automated controls and inspection systems that eliminate static charge, visible particles, and subvisible particles to well below USP 789 requirements (Figure 4). In-line deionizer systems ensure that vials nested in tub and tray configurations are free of static charge. Particles are not statically attracted to the vials during the final secondary packaging before shipment for sterilization.

SiO2 Vials are optimized for Fill-Finish Lines

Not only do SiO2 vials and syringes meet ISO standards, but they also do not affect the critical fill-finish step in packaging vaccines. We have re-evaluated factors that can affect fill-finish operations, including weight, surface finish, defect inspection, static change, and particle loads. Our findings show that our hybrid vials will be useful to companies expanding their fill-finish capacity and, ultimately, will be a contributor to the delivery of the COVID-19 vaccine to millions of people globally.

Ready to Rethink Glass?
Let SiO2’s Smart Vials help bring your new innovations to life and keep your patients safer. CONTACT HERE

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COVID-19

SiO2’s Smart Vials and Operation Warp Speed: The Development of a New Hybrid Packaging Solution for COVID-19 Vaccines

As the COVID-19 pandemic stretches over the second wave, over 50 million cases and 1.25 million deaths worldwide have been recorded. The global hunt for a vaccine is more important now than ever before, and scientists are researching at a breakneck pace. Through Operation Warp Speed (OWS), the federal government has accelerated the efforts of researchers and organizations to develop and distribute vaccines that are effective and safe.

The Food and Drug Administration (FDA) has provided guidance for fast-tracking vaccine development and market approval of a COVID-19 vaccine. So far, OWS has funded Phase III trials for three vaccines: Moderna’s mRNA-1273, University of Oxford and AstraZeneca’s AZD1222, and Pfizer and BioNTech’s BNT162.2 OWS is also partnering with more than 18 biopharmaceutical companies as they race to develop more vaccine candidates.

A Global Shortage of Traditional Vaccine Vials

The critical need to develop a safe and effective vaccine is just the first step. While Pharma is highly focused on vaccine development, companies also recognize that there’s a need for a sufficient supply of optimal packaging options to fill, store, and distribute billions of vaccine doses worldwide. In other words, we need enough vials to put the vaccine in, and we don’t have enough to go around.

For more than 100 years, pharma companies have used borosilicate glass in the manufacture of vaccine vials. Schott AG, one of the largest producers of this vaccine-grade glass, controls much of the market. But executives from Schott AG have admitted to The Wall Street Journal that they have received requests for a billion vials, and this is double what they can manufacture in 2020.

Moreover, borosilicate glass is facing a global shortage due to its unprecedented demand. Complications during production can also delay or shut down the manufacturing process. Glass vials can break due to glass-to-glass contact, and they don’t always break cleanly. The small broken particles can contaminate the vaccines. Contamination can also occur when glass delaminates from the inner walls of the container after prolonged exposure to some drug formulations. Furthermore, particles can interact with the active pharmaceutical ingredients in the drug formulation, which can reduce drug potency and form aggregates that are immunogenic to the patient. With so many vials in production, even a small percentage of defects can lead to severe consequences. The problems of unprecedented demand, breakage, and delamination of borosilicate glass are further confounded by questionable sealing integrity at cold storage temperatures.

Plastics have naturally received a surge of attention but have drawbacks that can compromise drug efficacy and stability. Although plastics outperform glass in terms of toughness and resistance to breakage, they are permeable to gas and water vapor, which means that the pharmaceutical active ingredients, excipients, or solvents in vaccines can interact with them easily.
To avoid a scenario where a company manufactures a safe and effective vaccine and does not have a sufficient supply of packaging materials, we need a strong alternative for borosilicate glass or plastic primary packaging.

A New Hybrid Packaging Solution


SiO2 Materials Science (SiO2) has spent the past 10 years developing a new hybrid packaging solution that is more effective than previous packaging materials. Championed by the Operation Warp Speed Initiative, the US government’s Biomedical Advanced Research and Development Authority (BARDA) awarded SiO2 a $143 million grant to accelerate the production of vials and secure a domestic supply for the COVID-19 vaccine.

This partnership has increased our scope by an exponential margin. Before the coronavirus outbreak, SiO2 could manufacture 14 million 10 mL vials per year. The BARDA contract has expanded our capacity to 40 million in June, 80 million in September, and 120 million in November.

Interlinking the Benefits of Glass and Plastic

Si02’s innovative primary packaging – in the form of 10 mL vials and pre-filled syringes – combine the benefits of glass and plastic without their respective drawbacks.

According to Christopher Weikart, chief scientist at SiO2, “We’re basically taking the best of glass and plastic and combining the benefits of both into a hybrid material.”

How have we accomplished this? Si02 scientists chose a medical-grade, engineered cyclic olefin polymer, a type of plastic, as the base for the hybrid packaging material. Then they eliminated the characteristics of plastic that causes it to interact with the proteins found in a vaccine by engineering a chemically inert coating process. The process technology used to deposit the coatingremoves the air from the inside of plastic containers and fills the space with a special mixture of gases that contain the basic building block of silicon dioxide glass (SiO2) . The process applies an electromagnetic field across the container at very low pressure, activating the SiO2 gas and creating a layer of pure glass-like silica. The final product does not dissolve or interact with the compounds in a vaccine.

SiO2 is not a combination of glass and plastic; it’s more than that. The layer of pure glass-like silica mimics glass by offering the oxygen and moisture barrier properties of glass without the risks of breakage and delamination. For example, the oxygen barrier performance of the coating is retained even after 1000 lbs. of compression force is applied to the coating. Another benefit of our hybrid packaging material is that it has the optical clarity and appearance of glass, but is about half the weight. Lastly, the glass-like silica coating is chemically inert and resistant to a wide range of pH values and excipients. 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.

Why Si02 is the Future of Primary Containers


Long-established glass manufacturers typically require up to 18 months to scale their manufacturing operations. But at SiO2, it only takes four months. This means that pharma companies can increase the bandwidth for making more COVID-19 vaccines and, hence, save more lives. This also implies that Si02 is first-to-market with an innovative product that is more effective than its predecessor.

So far, SiO2 has shipped its hybrid vials to five vaccine manufacturers. Although sponsored by BARDA, SiO2 has the liberty to support both BARDA-funded and non-BARDA-funded pharma companies.
As many wait for a COVID-19 vaccine, we hope that SiO2 can be instrumental and play a significant role in the quest to prevent the spread and fatality of the SARS-CoV-2 virus that causes COVID-19.

Ready to Rethink Glass?

Let SiO2’s Smart Vials help bring your new innovations to life and keep your patients safer.

CONTACT HERE

References

  1. CDC. Frequently Asked Questions about Vaccination. Centers for Disease Control and Prevention. Published February 11, 2020. Accessed November 8, 2020. https://www.cdc.gov/coronavirus/2019-ncov/vaccines/faq.html
  2. COVID-19 vaccine tracker. Accessed November 8, 2020. https://www.raps.org/news-and-articles/news-articles/2020/3/covid-19-vaccine-tracker
  3. Hinshaw JSH and D. Coronavirus Vaccine Makers Are Hunting for Vital Equipment: Glass Vials. Wall Street Journal. https://www.wsj.com/articles/coronavirus-vaccine-makers-are-hunting-for-vital-equipment-glass-vials-11592317525. Published June 16, 2020. Accessed November 8, 2020.
  4. Coronavirus vaccine: Inside US $347m contracts to solve vial shortages – Business Insider. Accessed November 10, 2020. https://www.businessinsider.com/coronavirus-vaccine-glass-shortage-operation-warp-speed-corning-sio2-2020-6
  5. 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
  6. 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.
  7. 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.
Categories
COVID-19

How SiO2 Smart Vials Preserve the Drug Stability For COVID-19 Vaccines

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
Conclusion

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.

Ready to Rethink Glass?

Let SiO2’s Smart Vials help bring your new innovations to life and keep your patients safer.

CONTACT HERE

References

  1. 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
  2. Guidelines on Packaging for Pharmaceutical Products. Accessed November 10, 2020. https://www.who.int/medicines/areas/quality_safety/quality_assurance/GuidelinesPackagingPharmaceuticalProductsTRS902Annex9.pdf
  3. 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.
  4. Jones SW. Introduction to Integrated Circuit Technology. Published online 2001:21.
  5. 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.
  6. 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.
  7. 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
Categories
COVID-19

How Do Si02 Smart Vials Benefit From Cryo and Cold Storage Container Closure Integrity?

The Significance of Container Closure Integrity (CCI)

Establishing a well-defined container closure system preserves the sterility of a drug over its shelf life. Container closure integrity (CCI) is important because it determines product and consumer safety. To keep patients safe, pharma manufacturers should implement container closure systems that avert contamination from microorganisms, reactive gases, and other substances.

Although scientific evidence shows that the benefits of vaccines far outweigh the risks, historically, there have been several major concerns about the safety of vaccines. One notable case of a vaccine recalled by Merck & Company, Inc. highlights the potential risk of contamination. In 2007, Merck recalled 1.2 million doses of Haemophilus influenzae type b (Hib) due to concerns about potential contamination with B. cereus, a type of bacteria that causes food poisoning or gastrointestinal infections. Fortunately, there were no reports of infection from B. cereus in the individuals that received the vaccine.

One way to ensure the sealing integrity of vials is through testing. Container Closure Integrity (CCI) testing is an assay that helps companies evaluate whether their container closure systems are sufficient for maintaining a sterile barrier against potential contaminants.

Properties that Affect Storage Container Closure Integrity

Threats to CCI include the type and design of materials used in packaging the drug, the equipment used in the sealing process, the method applied during sealing, and the environment or temperatures in which the vials are stored. Additionally, the vial dimensions, assembly, and exposure to temperature extremes can make it difficult to measure, predict, and control CCI.

Certain COVID-19 vaccine formulations in development (for example, mRNA and DNA) require cold chain storage as low as -80 °C using dry ice.3–5 Many cell and gene therapies demand cryogenic storage with liquid nitrogen that approaches -196 °C.6,7 These storage requirements further complicate CCI for vial closure systems that were never designed for such extreme conditions.

Advantages of the Cyclic Olefin Polymer Molding Process for Manufacturing SiO2 Vials

SiO2 vials have unmatched advantages because of the tight dimensional control inherent in the cyclic olefin polymer molding process. The dimensions of cyclic olefin polymer vials can be controlled to extremely tight tolerances that are ten to one hundred times lower than that of tubular or molded glass vials. Improving the dimensional precision has reduced and controlled stacking tolerances from the stopper and vial. This has resulted in a better fit and seal in all SiO2 vials.

sio2 vial

Furthermore, the thermal coefficient of expansion of the cyclic olefin polymer is lower than elastomeric rubber stopper materials and is more closely matched to that of borosilicate glass. This means that the amount of shrinkage at cold or cryogenic temperatures will be more like the rubber stopper than glass and therefore reduce the risk of separation that could lead to CCI failure.

The coating itself does not interfere with sealing integrity nor dimensional variability. The total thickness of the barrier coating system is less than half a micron, which is at least two and a half times below the dimensional variability of the polymer vial. Additionally, the deposition of the coating conforms to the internal surface of the cyclic olefin polymer vial. This means that the texture or roughness of the vial surface is completely unaltered after the coating is deposited. The rubber stopper, therefore, seals against the coating as it would against the cyclic ole fin polymer.

The risk of the barrier coating system delaminating from the vial wall at cryogenic storage conditions was shown to be robust down to -196°C. SiO2 vials were completely immersed in liquid nitrogen for 6 hours and brought back to room temperature. The exposure to liquid nitrogen causes the polymer vial to shrink, putting the barrier coating system under compressive stress at the surface. However, the oxygen transmission rate (OTR) measured before and after liquid nitrogen immersion was essentially the same as shown in Figure 2. This experimental evidence suggested that the barrier system was well-bonded and intact on the surface of the vial.

Quality Control: CCI Cold Storage Testing at SiO2

SiO2 has developed quality control procedures in collaboration with Lighthouse Labs for cold storage CCI testing. Cold storage CCI evaluations were conducted on 10 mL SiO2 vials. The vials were sealed with West Novapure stoppers at three different residual seal force settings and stored on a bed of dry ice at -80°C. The residual seal force is the amount of force exerted on the vial opening by the rubber stopper after the crimp cap is applied.

The CCI – determined by the CO2 headspace partial pressure measurement – of unfilled SiO2 vials was low and unchanged after six months of storage compared to positive control vials with a 5-micron hole drilled through the wall by a laser (Figure 3).
The CCI cold storage testing will continue to be monitored for at least one year. Separately, a cell therapy customer developing a viral vector vaccine already reported one year of drug stability in SiO2 2 mL vials stored at -80°C filled with their proprietary formulation [unpublished communication].
Implications for COVID-19 Vaccines: The Closure Integrity of SiO2 Vials

Given that previous vial closure systems were not designed for extremely cold temperature storage, SiO2 offers an advantage for the storage and transportation of COVID-19 vaccines on a global scale.

The barrier coating system on the inside of SiO2 vials do not delaminate at cryogenic storage conditions, even when under compressive stress. Therefore, the novel hybrid barrier coating used in manufacturing SiO2 vials have very strong bonds that will hold up under tough storage and transportation conditions. SiO2 is well-positioned to supply high-quality products to regulated markets at very high volume at extreme temperatures.

Ready to Rethink Glass?

Let SiO2’s Smart Vials help bring your new innovations to life and keep your patients safer.

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References

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