However, certain issues remain that are unique to glass and which, if unresolved, could undermine its market position in the longer term. During Pharmapack 2017 in Paris on February 1st, Kyle Hoff, Applications Engineering Manager at US-based global glass giant Corning, outlined three that the company has been addressing in recent years: delamination, breakage and particulates.
Delamination of a borosilicate glass vial results when the converting process causes a chemical heterogeneity on the inside of the vial after forming, Hoff explained. Boron, which is added during converting to aid the flow of the glass, can volatilize out and redeposit by condensing on the cooler regions.
During subsequent flame-working steps, it is reincorporated into parts of the vial, typically the neck and flange, which leads to a heterogeneous surface. When this skin layer is exposed to the liquid in the drug formulation, delamination can occur.
“The problem can be mitigated by means of engineering but Corning sought to eliminate it entirely by replacing borosilicate with aluminosilicate glass, which does not generate the converted species, and this eliminates the propensity to delaminate,” Hoff said. The company has evaluated aluminosilicate with multiple different vial sizes and fining agents— tin oxide can be a useful alternative to arsenic and chlorine, he noted – and achieved a glass with no or far fewer flakes visible.
Corning has also worked with industry partners on the issue of breakage during filling or transportation post-filling or at the hospital. “For glass to break requires two things,” Hoff observed. “One is surface flaws, which can occur at pretty much any time during the process of making glass. The other is intensive stress – for example, when a jam on the filing line causes the bottles or vials against each other.”
Simulation of this process in the lab suggested that one way to increase the strength of glass is to use ion exchange. Containers are submerged in a special salt batch, setting off a chemical reaction in which, sodium atoms in the glass are replaced by larger potassium atoms, improving the compressive strength of the surface, so that a higher level of stress is needed to cause the flaw to lead to a breakage. In tests, the new strengthened glass failed at loads of about 10,000 Newtons, against 600 for traditional borosilicate.
Particulate contamination occurs from several sources on the filling lines. These include glass-to-glass damage, introduced where there is a breakage on one container generating fragments or particles that get into others, and line interventions, when operators have to go into clean up or adjust lines. In the process, they disrupt the laminar air flow, raising particulates up and depositing them back down in open vials.
“A new source that has not been considered or characterised much is glass-to-glass contact on lines where vials are pushed next to each other and have a high coefficient of friction on the surface,” said Hoff. This creates scratching between the vials, which optical microscopy shows can lead to a fair amount of material being scratched from the surface of the vial or, even more substantially, chips being created and removed.
Corning carried out a laboratory test to scratch vials and replicate the damage it had seen on filling lines. When looking at the surfaces with optical microscopy, it found that creating vials with a special low coefficient of friction surface does not generate the same levels because the surface is not damaged to anywhere the same degree as with standard borosilicate vials.
The company is now working with partners to determine what benefit low coefficient of friction surfaces can offer. One found an 85% reduction in particle levels in their isolators using the new technique, translating to a 42% reduction in particles in solution.
Another showed a 95% reduction in particles/m3 of air going through the detector and a 50% reduction in spikes over a one-week, 1.6 million vial campaign. An added benefit, in a third study, is that fewer operator inventions are needed, downtime is reduced and there is a lower (about 21%) rejection rate for cosmetic reasons once the vials have been filled.
Nice Insight, established in 2010, is the research division of That’s Nice, A Science Agency, providing data and analysis from proprietary annual surveys, custom primary qualitative and quantitative research as well as extensive secondary research. Current annual surveys include The Nice Insight Contract Development & Manufacturing (CDMO/CMO), Survey The Nice Insight Contract Research - Preclinical and Clinical (CRO) Survey, The Nice Insight Pharmaceutical Equipment Survey, and The Nice Insight Pharmaceutical Excipients Survey.