If the COVID-19 pandemic has a theme, it’s shortages. At times, there hasn’t been enough personal protective equipment for front-line workers and caregivers or ventilators for the sickest victims. In addition, limitations related to testing, lab capacity, and contact tracing continue to make it difficult to identify those exposed to the virus in a timely manner.
When a vaccine becomes available, will the packaging supply chain be better prepared? Suppliers are working hard to prevent shortages and bottlenecks. Because many organizations are developing vaccine candidates that look promising, there is a possibility more than one vaccine will be commercialized. If these vaccines rely on different administration routes (e.g., inhaled, oral, transdermal, and injectable), then demand for primary packaging can be extended across multiple packaging formats. Relying on a combination of blow-fill-seal syringes, glass-coated plastic vials and syringes, fused-quartz vials, microneedle array patches, prefilled glass or plastic syringes, traditional glass vials or syringes, bottles for solid dosage forms, or metered-dose inhalers may be needed to quickly deliver the billions of COVID-19 vaccine doses that will be required.
Another shortage-mitigation factor is that packaging suppliers and fill/finish operations were investing heavily to meet rising demand before the pandemic started and have accelerated efforts in recent months to ensure they will be ready to address the skyrocketing need generated by the approval of COVID-19 vaccines and treatments (1). “We are confident that there will be enough primary packaging containers available globally to deliver one or more vaccines safely and fast to the people,” says Stefan Marc Schmidt, vice-president of global sales and marketing at SCHOTT Pharmaceutical Systems.
Glass vials and syringes
Borosilicate glass is the most widely used material to package vaccines and has been used for more than a century. Approximately 50 billion borosilicate glass containers are made annually worldwide for use with a wide variety of vaccines and treatments (2). With well-established infrastructure and long-term fill/finish experience, most COVID-19 vaccines will likely use this packaging format. In fact, SCHOTT, which operates a global validated production network with 20 plants and more than 600 production lines for pharma glass and packaging, already has delivered millions of glass vials to SARS-CoV-2 programs including supplying three out of every four COVID-19 vaccine projects undergoing Phase I, II, and III testing (3).
Schmidt believes demand for glass vials generated by the approval of one or more COVID-19 vaccines can be met without causing shortages for non-COVID-related vaccines, treatments, and diagnostics. He reports, “We are closely monitoring the demand for vials. The supply process for pharmaceutical vials itself has not changed and is based on standardized procedures. As a packaging supplier, we know with several months lead time how many vials to deliver and when to deliver them. This [lead time] gives us enough room to prioritize our production. Since we produce the pharmaceutical glass tubing for the packaging ourselves, we are also able to adjust the capacities for glass production in advance, which also benefits packaging manufacturers who do not have their own glass production facilities.”
SCHOTT and other producers of borosilicate glass containers, such as Stevanato Group, Gerresheimer, Corning, and DWK Life Sciences, have been working to boost capacity and quality for some time (2, 4). SCHOTT announced in 2019 it would invest approximately $1 billion. “We are on track to increasing tubing capacity by roughly 40,000 tons by the end of 2021,” says Fabian Stöcker, vice-president of strategy and innovation at SCHOTT Pharmaceutical Systems. “That equals roughly seven billion pharma packaging containers,” he explains. The investment program enables rapid ramp-up of production. “Since our sites are already validated by the authorities and by major pharma companies, our expansion is happening at a very fast pace,” reports Stöcker.
DWK Life Sciences has more than doubled production capacity for borosilicate glass vials at its ISO 9001-certified plant in Rockwood, TN. Specific upgrades include the addition of automated tube loaders with vertical loading capabilities; automated, touchless manufacturing processes; and Class 8 certified cleanroom robotic packing. “By converting to state-of-the-art lines, complete with dimensional and cosmetic vision inspection equipment, we’ve increased productivity in the plant and are delivering industry-leading quality for glass vials,” said Rick Schwartz, senior vice-president of marketing and sales at DWK Life Sciences (4).
Corning produces both borosilicate glass tubing and coated aluminosilicate Valor Glass vials. For Valor Glass vials, an ion-exchange process helps minimize breakage, cracks, and particulate contamination, while the coating lowers the coefficient of friction and eliminates cosmetic flaws. Despite eliminating boron and adjusting the ratios of other ingredients, Valor Glass meets the current United States Pharmacopeia (USP) Type I hydrolytic criteria and has low extractable concentrations (5).
Valor Glass vials can enable drug/vaccine manufacturing fill lines to run at much higher speeds while maintaining high operational efficiency (80+%) and improved yields compared to conventional containers, reports Corning. “Increased speed improves capacity for producing COVID-19 countermeasures,” notes Brendan Mosher, vice-president and general manager of Corning Pharmaceutical Technologies. He continues, “We . . . believe that both [borosilicate and Valor Glass] can play an important role in the supply chain for COVID-19 pharmaceutical products.”
In mid-October 2020, Corning projected it would ship tens of millions of vials in the coming weeks to multiple Operation Warp Speed vaccine developers. Mosher reports, “We’ve quadrupled capacity at our Big Flats manufacturing facility in New York and will be able to ship enough vials to support hundreds of millions of COVID-19 vaccine doses next year. We will continue to scale manufacturing to meet increasing customer demand over the next three years and beyond.”
A new glass furnace installed at its Vineland, NJ facility was scheduled to begin serving customers in November 2020. Mosher says, “With the US government’s investment that we announced in June, we will be able to scale manufacturing to meet increasing customer demand. This will result in a three- to four-fold capacity increase by the end of this year, and a 10-fold increase by the end of next year as our Durham, NC, manufacturing footprint comes online in the second half of 2021. Per the agreement ... with BARDA [Biomedical Advanced Research and Development Authority, part of the US Department of Health and Human Services’ Office of the Assistant Secretary for Preparedness and Response], Corning will provide priority access to designated BARDA vaccine and drug development partners.”
Glassmakers also have focused on preventing supply chain problems. At SCHOTT, Schmidt says, “When the pandemic started, we knew that we needed to make sure that our products were getting to customers without delay.” Incoming supplies were secured and authorities were alerted to ensure the products would be regarded as essential and shipments would not be stalled in transit.
Andrea Zambon, marketing and product management director at Stevanato Group, reports, “Since the outbreak of COVID-19, we’ve been securing supplies. We’ve increased our staff in production and redesigned shifts [so they could continue] to produce without any stop and deliver our products while preserving our staff’s health and safety. We’ve proactively invested by adding significant capacity as much as we could in our worldwide operations for the production of bulk and ready-to-use vials. We’ve been able to act fast, installing the latest generation of our glass converting lines, which we produce in-house through our company Spami.”
Fused-quartz vials
Stevanato Group also is collaborating to supply Pur Q fused-quartz vials from Momentive Technologies in Stevanato’s EZ-fill packaging format, which provides ready-to-use containers for aseptic fill/finish operations. The EZ-fill configuration gives pharma companies clean, sterilized, and depyrogenated ready-to-fill containers with a high level of machinability and compatibility with existing fill/finish technology. “Pur Q vials conform to the ISO vial dimensional requirements, which ensure their compatibility with all the leading stopper/closure systems ... used on these vials, in the pharmaceutical industry today,” explains Robert Koch, global commercial director at Momentive Technologies.
Made from 99.995% pure silicon dioxide (SiO2), the fused-quartz vials have an exceptionally inert, nonreactive surface that virtually eliminates any risk of interaction with packaged drug formulations (6). Koch reports, “The raw materials are very tightly controlled and then subjected to a number of refining steps that result in the consistent, industry-leading purity. Each batch of raw material undergoes a trace elemental screen using ICP-OES [inductively coupled plasma-optical emission spectrometry] before it is released for production,” he adds.
In comparison, Koch says, “Conventional Type I vials in use today are typically 75–80% SiO2 with the remaining components comprised of additives, particularly from the boron, alkali, and alkaline earth groups. While borosilicate Type I glass vials are an effective packaging material for many of the pharmaceutical drugs on the market today, Pur Q vials are ideal for sensitive drugs where interaction with even trace elements could be detrimental.”
EZ-fill secondary packaging stores vials safely in a tray or nest-and-tub configuration for efficient filling, while minimizing glass-to-glass contact and the chance of breakage, cosmetic defects, or particulate generation during fill/finish operations. The ready-to-use format allows drug makers to screen early-stage drug formulations and scale up to full production, without changing the container or filling process (6). “Being a ready-to-fill solution, SG EZ-fill can speed up the time to market,” explains Fabio Bertacchini, director of product management at Stevanato Group.
In addition, a low (near zero) coefficient of thermal expansion makes the Pur Q fused-quartz vials extremely resistant to thermal shock and therefore compatible with any storage temperature. “As an example, in other industrial applications, fused-quartz tubing is regularly exposed to temperatures of -196 °C,” says Koch, noting that storage temperatures for drug products in fused-quartz vials are more likely to be limited by stopper and closure system limitations.
Stoppers and seals
Many of the vaccine candidates rely on a vial format, which requires stoppers and seals. To prevent shortages of these components and bottlenecks in vaccine distribution, West Pharmaceutical Services, a supplier of stoppers and flip-off seals with 25 plants worldwide, is taking steps to ensure adequate supplies.
“We are working with our suppliers so we will have the raw materials needed to meet these huge demands, and we are investing in capacity and flexibility to quickly meet market needs,” reports Whitney Winters, senior director, strategic marketing, Biologics at West Pharmaceutical Services. “In some cases, we are talking with suppliers and customers daily,” she reports.
In addition, she says, “We are spending a lot of time in scenario planning for next year to ensure we’ll be able to meet the needs of COVID-19 vaccines, treatments, and diagnostics while still supporting makers of non-COVID-19 vaccines, treatments, and diagnostics.” As a result, West Pharmaceutical Services is scaling up both equipment and labor. Winters notes, “In-shoring is one of our top priorities. We’re adding production lines and team members to cover additional shifts and capacity ramp-up. Some plants already run 24/7, others are adding shifts. We have two priorities—to ensure the health and safety of team members and to supply the market for COVID-19 and non-COVID-19 products without interruption.”
One West product, the FluroTec stopper, is designed for sensitive biologics. A fluoropolymer barrier film, applied to the elastomer, provides a protective layer that separates the product from the stopper. The stoppers can be autoclaved by West and provided as a sterile component or sterilized at the fill/finish location. Seals also can be delivered as a sterile component after gamma sterilization by a third-party provider.
E-beam process could offset sterilization constraints.
Sterilization of primary packaging, an essential step in delivering a safe, beneficial vaccine, ranks as a critical factor in the timely distribution of a COVID-19 vaccine. Options include gamma radiation, e-beam, ethylene oxide (EtO), and x-rays, among other technologies. Greater adoption of the e-beam sterilization process could help prevent bottlenecks associated with sterilization constraints.
To read this article, go to www.pharmtech.com/view/e-beam-process-could-offset-sterilization-constraints.
The proven FluroTec technology and the company’s well-established NovaPure brand of stoppers provide vaccine makers with a high level of confidence the packaging will pass container/closure integrity and stability tests, says Winters. “Right now, vaccine makers need tried-and-true packaging,” she says. To help save time, West’s Analytical Services Lab can assist with container/closure integrity testing.
Bottles and blisters
Although many of the vaccine candidates are parenteral dosage forms, oral vaccines are under development by Vaxart and Merck (7, 8). If successful, these vaccines would likely rely on conventional high-density polyethylene or multilayer barrier bottles or blister packaging commonly used for solid dosage forms. “SARS-CoV-2, the coronavirus that causes COVID-19, is primarily transmitted by viral particles that enter through the mucosa—nose, mouth, or eyes—strongly suggesting that mucosal immunity could serve as the first line of defense. In addition, our vaccine is a room temperature-stable tablet, an enormous logistical advantage in large vaccination campaigns,” stated Andrei Floroiu, CEO of Vaxart (7). A self-administered solid-dose vaccine eliminates the need for sterile fill/finish operations and temperature-controlled handling and also offers sustainability benefits because it would eliminate the need to dispose of administration supplies, such as vials, syringes, needles, gloves, masks, and cotton balls (9).
References
- SCHOTT, “Answering the Hard Questions about Packaging Supply,” www.schott.com (July 21, 2020).
- SCHOTT, Stevanato Group, Gerresheimer, “Leading Pharma Packaging Companies Commit to Supply for COVID-19 Fight,” Press Release, June 16, 2020.
- SCHOTT, “Three Out of Every Four COVID-19 Vaccine Projects across the Globe Rely on SCHOTT Vials, Press Release, Sept. 8, 2020.
- DWK Life Sciences, “DWK Life Sciences Increases Glass Vial Production Capacity to Meet Increased Market Demand,” Press Release, Sept. 1, 2020.
- H. Forcinio, Pharm. Tech. 42 (7) 46-50 2018.
- Stevanato Group, Momentive Technologies, “Momentive Technologies and Stevanato Group Collaborate to Offer Pur Q Fused Quartz Vials in EZ-fill Configuration,” Press Release, October 13, 2020.
- Vaxart, “Vaxart’s COVID-19 Vaccine Selected for the U.S. Government’s Operation Warp Speed,” Press Release, June 26, 2020.
- PharmTech, “Merck Announces Acquisition, Collaborations for Developing COVID-19 Vaccines and Therapies, PharmTech.com (May 28, 2020).
- Vaxart, “The Pill against Pandemics, a Disruptive Oral Vaccine Platform,” Corporate Presentation, July 2020.
About the author
Hallie Forcinio is packaging editor for Pharmaceutical Technology, editorhal@sbcglobal.net.
Article Details
Pharmaceutical Technology
Vol. 44, No. 12
December 2020
Pages: 47–50
Citation
When referring to this article, please cite it as H. Forcinio, “Is the Packaging Supply Chain Ready?” Pharmaceutical Technology 44 (12) 2020.
