A Need for Higher Quality Packaging
Over the past several decades the biopharmaceutical industry has produced an impressive array of advances — new biological drugs for treating previously intractable diseases, high-speed filling lines to improve the availability and access of essential medicines for patients around the globe, and innovative new drug delivery systems that reduce errors and enhance patient compliance. At the same time, the standards for quality and safety have continued to rise steadily, driven by the same societal factors that affect other industries. These advances have put additional demands on the glass material used for drug storage and delivery.
Ironically, while the pharmaceutical industry has driven innovation in drug discovery and development, the glass containers in which medicines are housed have remained largely unchanged. Pharmaceutical manufacturers invest significant resources and time taking molecules from bench to bedside while the glass containers that store these life-saving products is largely dependent upon science originating from the 1930s (1).
Regulatory bodies and pharmaceutical manufacturers alike began to take notice of failures associated with current glass containers in 2011 when the U.S. Food and Drug Administration issued an advisory highlighting the risk of glass lamellae occurring in certain injectable drugs (2) due to a phenomenon known as delamination. Since then, glass packaging-associated recalls caused by delamination, glass particulates, and cracked containers that threaten drug product sterility have continued to plague the industry.
Drug recalls—and the associated risk of product shortages— are not the only challenges pharmaceutical manufacturers have faced. Concurrently, a longtime partner of Corning’s approached the company seeking a robust pharmaceutical glass that could survive high-speed fill and finish manufacturing. It became clear there was an industry need for a higher quality pharmaceutical glass packaging.
A Remarkable Glass Package
Corning Incorporated, a company with a 167-year history, has a long track record of partnering with industry leaders to solve difficult problems. The challenges of glass packaging drew widespread attention to the issues with conventional containers. Researchers at Corning also noticed and began to investigate the cause of the issues.
Corning identified boron as the root-cause for delamination (3) and engineered a boron-free composition called Corning Valor® Glass (4). Valor Glass is specifically designed for pharmaceutical use. It can be converted using traditional techniques without the risk of delamination.
While boron, a volatile element, is the root cause for delamination – the converting process also impacts a container’s chemical durability. During the converting process, specifically the step where the glass cane is parted (or separated) into two containers, the flame releases the boron from the glass network. Boron-containing compounds move around and evaporate as gas out of the glass network largely in the heel region of the vial.
Like a charged helium balloon sticks to a wall or object, the boron particles adhere to cool regions in the side-walls and heel (bottom) of the vial. A composition already rich in boron is now converted into its final format, with deposits that are richer in boron and sodium than the intended composition. This alters the glass chemistry of the container’s drug-contact surface. These areas rich in sodium borate, are vulnerable to delamination and ultimately pose risk to pharmaceutical product quality.
A Glass Designed for Pharmaceutical Use
Although glass is the ideal material for pharmaceutical containers, it is well-known to have some chemical interactions with drug products, especially over long periods of time. The industry assesses extractables and leachables concentrations of a container during stability studies, prior to introducing a drug to the market (5). Manufacturers monitor the profile and concentrations of extracted elements (e.g. boron, sodium) from the glass container during accelerated or shelf-life conditions. Differences in concentrations of extractables from glass containers are indicators of altered surface chemistry or contamination. This may lead to undesirable interactions with the drug product that could compromise potency, efficacy or stability.
Valor Glass offers improved overall extractable and leachable performance for parenteral packaging applications relative to comparable borosilicate containers (6). This means manufacturers see lower overall concentrations or quantities of elements extracting out of Valor Glass’ composition relative to borosilicate containers, reducing the risk of potential interactions between the container and the drug product, even for low-fill conditions.
Addressing Multiple Issues with a Complete Solution
Improving the quality of glass packaging through innovation has important benefits for the entire industry. Recent announcements by several glass packaging providers further reinforce the need for higher quality containers.
However, many of the new glass packaging products only address a single issue in a limited way, such as “controlling” delamination rather than eliminating it. Valor Glass has been designed to be a complete solution for a range of glass quality issues that affect products spanning from generic small molecule drugs to vaccines and biologics.
Not only does Valor Glass eliminate delamination, but it also dramatically reduces glass particulates (7) and prevents cracks (8) that may otherwise lead to a loss of drug stability and sterility. The boron-free composition of Valor Glass allows for uniform glass surface chemistry and enhanced chemical durability relative to traditional and delamination-resistant borosilicate glass containers.
Through a remarkable innovation in glass science, Corning has developed the only boron-free, arsenic-free product on the market specifically designed to meet the challenges of today’s pharmaceutical industry with a single solution.
Robert A. Schaut, W. Porter Weeks, Historical Review of Glasses Used for Parenteral Packaging. PDAJ Pharm Sci Technol pdajpst.2016 2016.007377
U.S. Food & Drug Administration, “Advisory to Drug Manufacturers: Formation of Glass Lamellae in Certain Injectable Drugs.” (2011) Available at: https://wayback.archiveit.org/7993/20170113073826/http:/www.fda.gov/Drugs/DrugSafety/ucm248490.htm
A Step Change in Pharmaceutical Glass Packaging Innovation. The Medicine Maker. (2019)
Robert A. Schaut, John S. Peanasky, Stephen E. DeMartino, and Susan Schiefelbein, “A New Glass Option for Parenteral Packaging.” PDAJ Pharm Sci Technol pdajpst.2014
Dennis R. Jenke, Linking Extractables and Leachables in Container/Closure Applications PDA J Pharm Sci Technol July/August 2005 59:265-281
PDA Letter. Extractables Testing of Aluminosilicate and Borosilicate Glass Containers. February 2018. Volume LIV. Issue Available at: https://www.pda.org/pda-letter-portal/archives/full-article/extractables-testing-of-aluminosilicate-and-borosilicate-glass-containers
Christopher Timmons, Chi Yuen Liu and Stefan Merkle, Particulate Generation Mechanisms During Bulk Filling and Mitigation via New Glass Vial. PDAJ Pharm Sci Technol pdajpst.2017. 007724
Robert A Schaut, Kyle C Hoff, Steven E DeMartino, William K Denson, and Ronald L Verkleeren, Enhancing Patient Safety through the Use of Pharmaceutical Glass Designed to Prevent Cracked Containers. PDAJ Pharm Sci Technol pdajpst.2017. 007807