Amy Meysner, a British specialist in ICP-OES analytical techniques who manages the chemistry department at Glass Technology Services (GTS) in the UK, tells me her professional background builds on a degree in Forensic Bioscience, and I can't help but pick her brain to dissect the good, the bad, and the ugly in today's primary packaging in the pharmaceutical industry.
For Meysner, the changes seen today in the pharmaceutical glass packaging market have been partly driven by the negative press coverage of high-profile recalls in 2010-2011 due to suspected delamination, and the following FDA advisory to drug manufacturers regarding the problem.
“Primary glass packaging has seen competition grow from alternative materials such as plastics,” she says. She also points out the numerous properties of glass, including its high resistance to chemical attack, has helped glass to remain the preferred primary packaging material for high-value drug formulations even in spite of the bad press from the recall episode.
“In response to the headline-grabbing recalls, manufacturers have been forced to prove the suitability of their glass containers through more stringent and detailed pre-use studies,” she adds. These tests, Meysner tells me, are aimed at ensuring the quality and suitability of the glass packaging for the intended use.
Commenting on the offerings that are now on the market, Meysner recognises that delamination “resistant” or “screened’ are new options available from all leading suppliers, and notes that alongside new packaging products, new glass formulations and “glass-types” have also emerged as proposed “solutions” for potential issues. "[These new options] are billed as even more highly resistant to chemical attack than borosilicate glass, including aluminosilicate and fused silica vials," she says.
Meysner says delamination has been a little-known phenomenon, unique to glass, for a long period of time, but the recalls brought the topic of glass delamination into the spotlight. “This triggered the industry and academia to re-evaluate old scientific information, such as the works of Violet Dimbleby starting in the 1920s,” she comments.
New type of glass formulations, such as aluminosilicate and fused silica vials, are billed as even more highly resistant to chemical attack than borosilicate glass
Lack of understanding between industries on matters such as risk, product compatibility, suitability, the potential for chemical interaction between substrates (such as glass), and the active pharmaceutical ingredients contained within, are contributing factors towards a delamination risk, according to Meysner.
Speaking more deeply about delamination, she recognises the issue is a big problem when it happens, but “it is not the most frequent problem we help clients to solve”, she tells me. “Delamination assessments are often carried out proactively, before a product enters the market, with the goal of preventing any recall scenario from arising,” she explains. Still, Meysner makes it clear that delamination is an event difficult to predict.
“A manufacturer can select a high-quality container and have it undergo all the recommended tests to prove its high performance; however, once in use, there is a potential for delamination. This is because delamination is due to the interaction of the drug product with the glass container and can be affected by numerous factors,” she explains.
For Meysner, the manufacturing protocol, the composition of the glass, and the drug product all need to be considered fully, as well as the storage conditions. “This is why the testing protocol must be robust when it comes to delamination, if an error is made and flakes are identified, the consequences can be enormous in terms of a product recall,” she warns.
Delamination is due to the interaction of the drug product with the glass container and can be affected by numerous factors
Fully aware of all these issues, GTS has been working hard to promote the debate with a series of open workshops that discuss the hot topics within glass production, strength, weaknesses and chemistry.
In October, for example, GTS hosted a workshop featuring Dr Desmond Hunt, the Principal Scientific Liaison at the USP, with a presentation titled ‘Evaluating the quality of your primary glass packaging: Focus on USP chapters <660> and <1660>’. For Meysner, the main take-home message from Hunt’s address was the importance of getting valuable input from the manufacturer/pharmaceutical companies to inform decisions when chapters are being consulted upon.
Desmond also revealed, Meysner tells me, that the USP is considering different analytical methods, which could potentially simplify the current grains, surface, arsenic and light transmission techniques. She recognises that technical committees in the European and US pharmacopoeia and the International Commission on Glass (ICG) are working with main players in glass supply and pharmaceutical producers to better understand the complex interplay of drug interactions, glass surface chemistry and process control, in order to predict issues before they happen.
Focus on pharmacopoeial verification
Meysner tells me that as a laboratory, GTS has noticed a change to the routine pharmacopoeial verification checks that are conducted. Many clients, she says, are moving in-house with independent analysis carried out as a due diligence step for each packaging category, when switching suppliers or when concerns are raised.
“We have seen many pharmaceuticals now approaching our laboratories for additional studies, such as elemental migration and delamination propensity, either as part of their initial packaging selection process or to support them during new product applications and authorisations,” she explains.
Outside of chemicals compliance and durability, GTS has seen increasingly tight product specifications and tolerances for primary glass packaging formats, closures and stoppers. This shift, Meysner says, is driven by highly concentrated formulations that require high-dosage accuracy, compatibility with filling lines, fast product changeovers and the need to guarantee closure integrity.
Leachables and extractables: big concern
Companies must be aware of the composition of all raw materials to ensure high-risk elements are not present in potentially harmful quantities in the glass. “If they are not present, then there is no potential for extraction,” she notes.
However, when these high-risk elements must be present in the glass container, be it as a colourant or processing agent for the glass, then appropriate studies must be carried out to cover all potential risk elements. “Particular attention must be paid to the conditions under which the testing is carried out,” she explains.
Warehousing and logistics can be often overlooked, with cyclic temperatures and moisture control posing potential risks for inner surface contamination, misting or bloom
Time and temperature will have a significant impact upon leachables, Meysner adds and suggests companies question whether storage scenarios are being adequately represented or simulated in the test protocol.
“Warehousing and logistics can be often overlooked, with cyclic temperatures and moisture control posing potential risks for inner surface contamination, misting or bloom,” she warns.
Technology to the front
For Meysner, advancements in technology and instrumentation have allowed the sector to move away from traditional wet chemical techniques and develop more accurate and speedier methods.
“There is a wealth of research and development being carried out throughout the glass industry that present potential for improvements to packaging performance, whether this is in terms of strength, chemical durability or aesthetics," she says.
For Meysner, surface treatments that enhance the glass properties, such as strength and durability, are always being investigated and may provide an alternative solution to some of the new and improved, albeit costly, formulations.
Smart packaging technologies, including traceability, live feedback on storage conditions or simply communicating information to the end-user, are all being explored and present potential avenues for the future.
Glass has a strong position across different sectors due to its ability to be 100% recycled, and GTS is engaged with leading brands across these sectors on a range of topics, keeping its expertise at the forefront of science and technology.
N.B. This article is featured in the January 2020 issue of Cleanroom Technology. Subscribe today and get your print copy!
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