Not all flakes or particles are caused by delamination, argues Glass Technology Services
Lamellae sample in suspension following prolonged, aggressive attack on glass surfaces
The current focus on delamination could be clouding the bigger pharmaceutical glass packaging picture and narrowing the options for potentially more cost-effective solutions, a leading glass analyst says.
Daniel Capon of Glass Technology Services (GTS), a centre for glass research and development and an independent glass laboratory and consultancy accredited to ISO 9001, 14001 and 17025 quality standards based in Sheffield, UK, says there is a trend to label any perceived problem with glass used in pharmaceutical packaging as delamination, when in fact many problems result from other causes, some of which are potentially simpler and cheaper to remedy.
'It is vital not to make generalisations based on recent product recalls,' says Capon. 'Glass containers remain the preferred choice for most medicinal products and risk can be mitigated and controlled to ensure both product quality and patient safety.
'Where I think the industry could be missing a trick is in not assuming delamination in the first instance, but instead analysing each appearance of flakes or particles to address the root cause.'
Based on experience of samples sent to GTS for delamination analysis, Capon says that often what look like tiny glass fragments, flakes (lamellae) or deposits, are actually naturally occurring compounds that have precipitated out of solution and dissolved back into the solution by the time the sample reaches the GTS laboratory, or they are foreign bodies introduced during subsequent production and filling processes or by the end user.
The true source of delamination in the case of borosilicate type 1 glass is flame working of the glass which can cause boron to volatilise from the surface of the glass. This leaves behind a silica-rich surface layer which has a different thermal expansion to the bulk glass, and this in turn can cause the surface to flake off when exposed to variances in temperature, for example.
SEM image showing surface attack of flame worked region on vial sidewall
In the case of soda-lime-silica type III glass, delamination is used to describe the effect which occurs due to constant attack of the glass surface from the liquids in the container, which leaches the alkaline components of the glass and results in a more alkaline solution.
This in turn increases the rate of attack until a skin of predominately silica is left on the glass surface, which can eventually detach and be seen as very thin shimmering particles within the solution. This effect can even occur with glass which has good durability where exposed to high or cyclic temperatures.
'Independent testing can provide essential information to demonstrate due diligence and compliance, in the event of any litigation,' says Capon.
'It could also avoid costly product recalls. At the very least, it can ensure that you are focusing on solving the right problem.'
Recent changes to the United States Pharmacopoeia (USP) include a new chapter <1660> regarding delamination propensity pre-screening to assess compatibility between drug products and their packaging.
Comparative SEM image showing bulk glass on vial sidewall without any sign of surface attack
This pre-screening package was made available by GTS in advance of the USP’s publication last December and an article regarding the recent USP and European Pharmacopoeia (EP) changes is also available on the company's website.
GTS laboratories provide services throughout the biomedical and pharmaceutical sectors including quality assessment, pharmacopoeia, foreign body, composition and failure analyses and the research and development of specialist bioactive glass and ceramics. The laboratory is UKAS ISO:17025 accredited and also registered with the US FDA under the GDUFA for API/FDF testing.
The team employs a range of analytical techniques, including SEM-EDS (scanning electron microscopy – energy-dispersive X-ray spectroscopy); WDS-XRF (wavelength dispersive spectroscopy X-ray fluorescence); GRIM (glass refractive index measurement); FTIR (fourier transform infra-red) spectroscopy; ICP-OES (inductively coupled plasma optical emission spectroscopy); UV-Vis spectroscopy and FEA (finite element analysis).
In many cases the data from different analysis techniques provides information which enables the GTS technical team to determine the root cause of issues and suggest remedial or preventative solutions.