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Pharmaceutical Glass Containers
Testing as per USP <660>
As per USP <1660>, Glass delamination may be described as the appearance of thin flexible flakes of glass (or lamellae) that can range in size from <50 µm to 200 µm in a drug product solution. This is a serious quality issue and can result in a product recall. The appearance of glass lamellae is a lagging indicator of a strong interaction between the drug product and the inner surface of the glass. Delamination is thus an indicator of glass corrosion.
Tests for delamination combine the visual examination of the solution, a microscopic examination of the vial's internal surface and stress testing to assess the delamination potential of the glass.
Glass containers for pharmaceutical use are intended to come into direct contact with pharmaceutical products
- Glass containers – Type I (e.g. Borosilicate): parenteral and non-parenteral uses
- Glass containers – Type II (e.g., treated soda-lime silica): Most acidic and neutral aqueous products for parenteral and non-parenteral uses. These may be used for Alkaline parenteral products where stability data demonstrate their suitability.
- Glass containers – Type III (e.g., soda-lime silica): usually are not used for parenteral products or for powders for parenteral use, except where suitable stability test data indicate that containers meeting Type III performance are satisfactory.
Glass containers must comply with their respective specifications for ▲▲ (IRA 1-Oct-2023) surface hydrolytic resistance ▲as noted in Table 1 and Table 2.▲ (IRA 1-Oct-2023) Type I or Type II containers for aqueous parenteral products are tested for extractable arsenic.
The Glass Grains Test combined with the Surface Glass Test for hydrolytic resistance determines glass ▲performance.
Table 1. Determination of Glass ▲Performance▲ (IRA 1-Oct-2023)
| ▲Performance▲ (IRA 1-Oct-2023) Type | Test | Reason |
|---|---|---|
| I, II, III | Glass Grains Test | Distinguishes Type I ▲▲ (IRA 1-Oct-2023) from Type II and III ▲▲ (IRA 1-Oct-2023) |
The inner surface of glass containers is the contact surface for pharmaceutical preparations, and the quality of this surface is determined by the Surface Glass Test for hydrolytic resistance. The Surface Etching Test may be used to determine whether high hydrolytic resistance is due to chemical composition or to surface treatment. Alternatively, the comparison of data from the Glass Grains Test and the Surface Glass Test may be used in Table 2
Table 2. Determination of Inner Surface Hydrolytic Resistance
| ▲Performance▲ (IRA 1-Oct-2023) Type | Test | Reason |
|---|---|---|
| I, II, III | Surface Glass Test | Determines hydrolytic resistance of inner surface; distinguishes between Type I and Type II containers with high hydrolytic resistance and Type III containers with moderate hydrolytic resistance |
| I, II | Surface Etching Test or comparison of Glass Grains Test and Surface Glass Test data | Where it is necessary, determines whether high hydrolytic resistance is due to inner surface treatment or to the chemical composition of the glass containers |
Why does glass delamination occur?
The process of forming tubular vials and ampuls requires heating. During formation of the neck and particularly the base, the temperature of the inner surface of the containers can exceed the evaporation point of some of the glass components such as alkali borates. In some cases, the glass can phase separate during forming, creating non-homogenous surface chemistry on the interior of the container. Also, the inner surfaces of glass ampuls, vials, and bottles may undergo additional treatments causing change in glass surface chemistry and uniformity.
Glass Grains test: 500grams.
Surface Glass Test: 48 containers
Surface Etching Test
The Surface Etching Test is used in addition to the Surface Glass Test when it is necessary to determine whether a container has been surface treated and/or to distinguish between Type I and Type II glass containers.
The results obtained from the Surface Etching Test are compared to those obtained from the Surface Glass Test. For Type I glass containers, the values obtained are close to those found in the Surface Glass Test. For Type II glass containers, the values obtained greatly exceed those found in the Surface Glass Test; and they are similar to, but not greater than, those obtained for Type III glass containers of the same filling volume.
MPURITIES
Use as the Test Preparation 35 mL of the water from one Type I or Type II glass container, or, in the case of smaller containers, 35 mL of the combined contents of several Type I or Type II glass containers, prepared as directed in the Surface Glass Test. The limit does not exceed 0.1 µg/g.
FUNCTIONALITY
Spectral Transmission for Colored Glass Containers
A UV-Vis spectrophotometer, equipped with either a photodiode detector or a photomultiplier tube coupled with an integrating sphere
Following the previously issued draft for USP General Chapter <660> Containers – Glass, the final version of the chapter was published and made official on 1st October 2023. In particular, the revision to General Chapter <660> changed the “composition based” glass type definition to one that is “performance based”.
From “composition based” definition to “performance based”
To disconnect the Type designation from the glass composition, in principle all glasses that pass the test for Type I can be used for drugs that require Type I glass as per the packaging section in their monographs.
| Glass Type | Composition | Use |
|---|---|---|
| Type I | Borosilicate Glass | This type of glass has borosilicate structure. It is ideal for containing all injectable preparations with acid, neutral and alkaline pH. It has good resistance to thermal shocks and can be sterilized before or after filling. Container of USP type I glass (Neutral borosilicate glass) |
| Type II | Soda-Lime-Silica Glass but with a suitable treatment on the inner surface to increase the hydrolytic resistance | This type of glass is a soda-lime glass which, by means of a special treatment, reaches the hydrolytic stability of type I glass on its surface layer of 0.1-0.2 um. It is suitable for acidic and neutral parenteral preparations. Type II glass container can be sterilized before or after filling. Container of USP type II glass (Treated soda-lime glass) |
| Type III | Soda-Lime-Silica Glass | This type of glass has average hydrolytic resistance. It is suitable for containing non-aqueous injectable preparations and those in powder form. It can also be used for non-parenteral preparations. Type III glass container should be sterilized by dry heat before filling. Container of USP type III glass (Soda-lime glass) |
CLL’s Solutions for Glass Delamination Study:
CLL uses a combination of techniques to carry out Glass Delamination Studies:
- Predictive Screening of Glass container
- Aggressive Screening of Glass container / Stress Testing
- Drug product interaction with Glass Container study – Accelerated conditions
A final Comprehensive Report is submitted to client with following details:
- Evaluation of Vials pre- and post- Stress Testing as per USP <1660> (3 stress solutions);
- Analytical Method Development and Validation data for ICP-MS for elemental analysis in Drug Product (Si, Pb, B, As, Ba);
- Evaluation of Final Drug Product filled container against Water filled control @ Accelerated Climate Conditions (ACC) time and temperature as per ICH – 6 month study.
The final glass delamination report allows customers to make decisions on:
- Glass container suitability determination for drug product
- Vendor Qualification
- Regulatory Submission
- Market recalls
Regulatory References: USP <1660>, <660>
Turnaround Time: 3 to 4 weeks for
- Delamination Predictive Screening: 2 Weeks
- Delamination Aggressive Screening: 2 Weeks
- Delamination Accelerated condition (3-6Months) Interaction Study: 3 to 6 months