Delamination analysis and propensity studies
Analytical support includes delamination and stability studies, investigations, accelerated attack simulations, long term studies and the analysis of glass delamination cases. Foreign body analysis is also available in the case of naturally occurring minerals, metals and other contaminants mistaken for delamination.
Glass Technology Services offers both investigative analysis where delamination is suspected and propensity studies for assessing delamination risk. This includes the suggested approach detailed in the United States Pharmacopoeia (USP General Information Chapter <1660>, 'Evaluation of the inner surface durability of glass containers') and referred to in the European Pharmacopoeia/Pharmacopée Européenne (EP) Chapter 3.2.1.
Please note: in the case of delamination of laminated flat glass, please see our product failure analysis services.
For further information, please see:
- Delamination analysis;
- Delamination propensity pre-screening and accelerated studies;
- Minimising delamination risk;
- About glass delamination;
- Product failure analysis;
- Glass defect and contamination analysis;
- Foreign body and fragment analysis;
- Pharmacopoeial verification;
- Further information and resources.
Expert glass support includes:
- Contract analysis, including evaluation of the inner surface durability of glass primary packaging, particle/flake filtration, filter paper observation and both scanning electron (SEM) and optical microscopy imaging;
- Ad-hoc analysis and Investigations where delamination is observed or suspected;
- Compatibility screening of primary packaging options;
- Initial screening, longterm and accelerated delamination propensity studies.
Initially, optical examination is carried out to ascertain the location and appearance of the suspect delamination, as this can be key information in determining the root cause. If there are particles suspended in the liquid, then this can be filtered out and, if there are particles attached to the glass surface, the glass item carefully prepared to enable further examination.
Using scanning electron microscope (SEM) the particles captured during filtration and particles from the glass surface are visually examined - as their appearance provides further information.
Energy dispersive spectrometry (EDS) is then carried out to analyse the composition of these particles. The information gained is then used to determine whether the particles are delaminate lamellae or other forms of product or surface contamination, to assess how they were formed and identify possible options for eliminating the problem on future production runs.
In some cases further information may be required in order to determine the root cause of the suspect delamination, this may include:
- Full compositional analysis to confirm the composition of the glass;
- Pharmacopoeial testing to confirm the durability classification; and,
- Quality assessment of the glass product to determine if it has been manufactured to specification.
Delamination propensity pre-screening and accelerated attack
Introduced into the USP in December 2013, propensity pre-screening assesses the risk of packaging to delaminate during its life-cycle under in-use conditions. This pre-screening package helps to evaluate differences in containers from different manufacturers, glass formulations, batch variations and post-forming processing and treatment conditions and typically includes the following assessments:
- Accelerated attack techniques with varying solutions; such as 0.9% KCl, 3% Citric Acid or 20mM Glycine as advocated in USP <1660>, or a range of other solutions to closely reflect the specific drug products;
- Cyclic heating and cooling;
- Chemical analysis of attack solutions;
- Visual assessment;
- Inner surface evaluation;
- Particle filtration and analysis.
Long term delamination and stability studies
A number of studies can be conducted - depending on the nature of the drug product, client requirements, market territory and relevant regulatory and pharmacopoeia requirements.
We work with our clients to understand their needs and ensure that the programme of analysis and study conditions are appropriate to the product, storage and use conditions.
Studies can be carried out at pre-determined temperatures, relative humidity levels, and time periods to simulate actual or accelerated ageing of filled products, predict delamination propensity and investigate the suitability or compatibility of different primary glass packaging formats, suppliers or drug formulations.
Minimising delamination risk
For all clients, we advocate a proactive approach to minimise the potential for delamination. This must always include: for pharmaceutical companies - the correct specification for the glass to ensure it's suitability for the pH of the product, the processing involved – including sterilisation and autoclaving processes – and both handling and storage conditions for the filled product; and, for glass manufacturers - ensuring that appropriate process controls are in place - including forming temperatures and correct annealing - and due diligence in the quality testing and assurance of their glass.
Quality assurance should dictate that glass quality, pharmacopoeia and durability analyses are conducted to assess the compatibility of the glass with the specific product that will be stored within the container - these are services that our team regularly provide on both an ad-hoc and contract basis. Glass quality can be assessed to assess the forming and annealing quality as well as mechanical performance, durability and migration testing can be provided using a range of simulants, of different pH, whilst pharmacopoeia testing will verify that the glass container meets the relevant international Pharmacopoeia Monographs, including USP and Ph. Eur, as required by the client. Each of these services are provided to a range of clients on a regular basis.
About glass delamination
- Type I – Borosilicate Glass; an essential step in the manufacture of pharmaceutical vessels from borosilicate tubing is flame working of the tubing to shape and form the finished packaging. This flame working has been demonstrated to cause the release of boron and sodium from the glass surface, which then condenses onto the glass surface. There is increased prevalence of delamination at both the heel and shoulder of vials made in this process – further supporting a relationship to the flame working. The resulting effect is that the glass surface is left enriched with silica with loosely attached condensates that can either remain or fall into the product within the vessel.
- Type III – Soda-Lime-Silicate Glass; delamination can occur when the surface of a soda-lime-silica type III glass container is attacked by the liquid suspension contained within it. The constant attack of the surface can result in the leaching of alkaline oxides from the glass surface - resulting in an increase of the solution’s pH. The effect is that the solution becomes increasingly alkaline and this, in-turn, accelerates the process until the point at which the surface forms a silica-rich skin.
It is this enriched silica skin that can then detach, or ‘flake’, from the surface and be observed as thin shimmering particles, ‘lamellae’, now commonly referred to as delamination.
The video, embedded below, shows a sample of glass lamellae in suspension and their shimmering appearance. Note that this is a concentrated example, generated after prolonged, repeated, exposure to extreme conditions:
Further information and resources
A UKAS accredited testing laboratory No. 1994, Glass Technology Services Ltd is also registered with the FDA under the GDUFA regulation. Our teams employ 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 analysis from different analytical techniques can provide data enabling the team to determine the root cause and suggest possible solutions.
A range of international standards and pharmacopoeias, including:
- USP 38-NF 33 - The United States Pharmacopoeia (USP), including Chapters <660>, 'Containers - Glass', and <1660>, 'Evaluation of the Inner Surface Durability of Glass Containers';
- Ph.Eur Ed - Chapter 3.2.1 - European Pharmacopoeia/Pharmacopée Européenne (EP);
- BP-Vol IV - The British Pharmacopoeia (BP);
- GOST 13905 - Russian Water Resistance Test;
- JP16 - Japanese Pharmacopoeia 16th Edition (JP).