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Material innovations enhance packaging for injectables.
Glass has long served as the traditional primary package for parenteral products. Unfortunately, glass breaks relatively easily and has been known to cause particulate contamination, to delaminate, and to interact with the drug product.
“Current issues with borosilicate glass containers such as breakage, cracks, and particles can lead to patient harm due to contamination, decreased drug efficacy, and drug shortages, as a result of recalls and manufacturing inefficiencies,” says John Tobin, vice-president of Commercial Operations at Corning.
He notes, “Current glass packaging has not innovated at the same or even a comparable pace to the scientific breakthroughs in biologic medicines and vaccines throughout the industry. Corning first became aware of glass quality issues with current pharmaceutical packaging for injectable drugs when a major pharmaceutical company and long-time customer asked us to develop a substantially more robust glass solution that also eliminates delamination and reduces particles. At the time, the United States Food and Drug Administration (FDA) had recently issued an advisory regarding the formation of glass lamellae in certain injectable drug containers. It became very clear to Corning that the industry needed a 21st-century glass package that provides the enhanced quality required to protect 21st-century drugs and, more importantly, provide more reliable access to vital medicines for patients around the world.”
To target the problems encountered with Type I borosilicate glass, Corning’s glass experts worked in collaboration with Merck and Pfizer to develop Valor Glass, an aluminosilicate glass, which is now commercially available. As a drop-in replacement for borosilicate glass, the new glass type is compatible with existing stoppers, caps, labels, and fill/finish lines.
Corning used glass chemistry and an ion-exchange process, and lowered the coefficient of friction of the surface to produce a glass that is inherently strong and damage resistant. Traditional borosilicate Type I glass contains a significant amount of boron. However, Tobin says, “When introduced to heat, such as during the converting process, the boron in the glass network becomes volatile and evaporates out of the glass, creating surface heterogeneities (regions of non-uniform glass composition) on the interior drug-contacting surface of the package. Corning intentionally removed boron from the Valor Glass composition because of its volatility, which can cause delamination. The other glass components are the same but the ratios are slightly altered to enable a high degree of chemical durability. As a result, Valor Glass has a pristine, chemically durable drug-contacting surface both before and after the converting process, effectively eliminating the root cause of delamination.”
An ion-exchange process also minimizes issues such as breakage, cracks, and particulate contamination. Despite the difference in chemistry, Valor Glass meets the current United States Pharmacopeia (USP) Type I hydrolytic criteria and has low extractable concentrations. Work is underway at USP to broaden the definition for Type I glass to include Valor Glass.
A protective coating on Valor Glass lowers its coefficient of friction and eliminates cosmetic flaws. Eliminating high-friction vial-to-vial contact protects the surface of the containers, results in a more uniform container flow, and enhances machinability. As a result, vials and cartridges run smoothly on fill/finish machines. Incidents with downed vials, jams, and broken containers are virtually eliminated, and throughput increases. For drug manufacturers, fewer line interventions mean less downtime and a decreased risk of contamination and quality defects. Trials on commercial filling lines have confirmed performance and shown a 96% reduction in peak particle counts, according to Corning.
Valor Glass has drawn the attention of more than 40 pharmaceutical companies. Tobin reports, “We initially thought interest would be for pipeline products, but it’s being looked at for marketed drugs as well. Corning has filed a drug master file for Valor Glass with FDA and will continue to work closely with pharmaceutical manufacturers to provide supporting information to facilitate adoption.”
Merck has announced plans to convert several products to Valor Glass pending regulatory approvals. At a press conference on 20 July 2017, Kenneth C. Frazier, Merck’s chairman and CEO, said, “Biologics today are on the leading edge of scientific innovation, and Valor Glass represents a similar advancement in materials science: glass that is purpose-built for medicines and vaccines.” At the same press conference, Valor Glass was described as a potential game changer. “Our initial trial results with Valor Glass show promise, and we are working with Corning to assess the full potential of this glass solution on products at several of our manufacturing sites,” said Ian C. Read, chairman and CEO at Pfizer (1).
As the designer of the composition, technology, and manufacturing platform, Corning manufactures and sells Valor Glass and oversees all purchases of it. In addition, established partners such as Gerresheimer and Stevanato Group, are providing converting and related expertise to speed delivery to the industry and patients.
With usage of prefilled syringes continuing to rise, Schott has doubled polymer syringe production at its syringe competence centre in St. Gallen, Switzerland. The new capacity started up in June 2017 and builds on a previous expansion. Additional capacity is being installed and will be operational in 2018 (2).
“Schott has optimized singular process steps based on our existing quality and production experience,” says Tom van Ginnecken, global product manager, Polymer Syringes at Schott. He notes, “Typical improvements involve the state-of-the-art technologies for transportation and handling to further reduce the risk of cosmetic defects. In addition, Schott is getting prepared for future pharma requirements in automation and data exchange.”
He explains, “We see a growing trend toward customized delivery systems. The first reason for this trend is the focus of pharmaceutical companies on orphan diseases. With a highly individualized injection solution, the pharmaceutical companies try to increase patient comfort and increase drug adherence by offering a tailor-made solution that is compliant with the patient group’s impairments and abilities. Another driver for more customized delivery systems is the need for product differentiation. More pharmaceutical companies use the injection device as a way to differentiate their drug in the market. In a fiercely fought market space with a lot of competition, such as generic drugs; this method of differentiation could mean the success or the failure of a drug. Also, the injection molding process of a polymer syringe inherently offers a broad range of customization possibilities.”
Polymer syringes offer advantages beyond customization and differentiation. The material maintains glass-like transparency, resists breakage, and offers excellent barrier properties to keep the medication stable throughout its shelf life. Schott polymer syringes are available in 1–50-mL sizes and delivered ready-to-fill in a nest-and-tub configuration. For more sensitive applications, Schott TopPac SD syringes feature a reduced extractable and leachable profile that ensures high drug stability (2).
Glass ampoules remain widely used to package injectable drugs, and demand is actually growing in emerging markets. Although typically used for high-volume, mainly small-molecule drugs, ampoules “could be interesting for biopharma products as well,” notes Neus Ferré, global product manager, Ampoules at Schott.
Schott’s glass ampoules combine dimensional stability with 100% inspection to suit either end of the spectrum: long runs at high speeds or flexible fill/finish systems for small batches. “At Schott, we are following a zero defect philosophy, resulting in ampoules of high and stable dimensional quality,” reports Ferré. She explains, “On the one hand, this is achieved by an excellent raw material-Fiolax Type I borosilicate glass-combined with a precise manufacturing process. On the other hand, we have invested in intelligent camera inspection systems that help to improve both cosmetic and dimensional quality even further.”
The DualFusion vial from Wheaton, now DWK Life Sciences, combines the best properties of both plastic and glass into one container. Using plasma-enhanced chemical vapour deposition, an organosilicate protective layer is fused with a silicon dioxide barrier layer that is fused to a cyclic olefin polymer (COP) shell to form a robust, covalently bonded material. The outer COP shell provides mechanical strength, protects against breakage, and can withstand temperatures from -196 °C to 121 °C without cracking. The inner barrier layer prevents permeation of oxygen, water vapour, and other gases, protects against delamination, and eliminates concerns over leaching of metal ions, which can compromise the integrity of vial contents (3).
Each ready-to-use, ready-to-sterilize DualFusion vial has a unique barcode for traceability and authentication. Applications include highly toxic drugs and biologics (4). More recently, there’s been interest for freeze-drying applications. The vial has a completely flat bottom that allows efficient temperature transfer from the lyophilizer to the drug product, and the vial’s barrier layer allows extended storage time, says Jeffrey Reid, strategic markets manager, DWK Life Sciences.
The increase in personalized medicine is driving growth in small batch fills. “Therefore,” says Reid, “pharmaceutical companies require smaller packouts of ready-to-use (RTU) packaging components.” To address this need, DWK Life Sciences will begin supplying RTU packaging components such as vials, rubber stoppers, and seals grouped together in one box with an average packout of 200 pieces per component. “This will allow our customers to shift to smaller fill runs and not have to worry about a large scrap rate of packaging components,” concludes Reid.
Hallie Forcinio is Pharmaceutical Technology’s Packaging Forum editor, firstname.lastname@example.org.
Pharmaceutical Technology Europe
Vol. 29, No. 9
When referring to this article, please cite it as H. Forcinio, "21st Century Parenteral Packaging," Pharmaceutical Technology Europe 29 (9) 2017.