Non-Conformity Identification and root cause determination

Glassware Flaw/ TR43 Defect Identification

Imaging
Using high resolution microscopy ranging from x20 to x5000 to determine morphology, length, location, surface, and ease of removability of non-conformity.

Contamination /  Material Characterization

Imaging
Using high resolution microscopy ranging from x20 to x5000 to determine morphology, length, location, surface, and ease of removability of non-conformity.

Elemental mapping
Uses EDS (Energy dispersive spectroscopy) to identify the elements that make up the non-conformity. (Ex: Fe, Ni, Cr to indicate presence of tooling steel)

Organic identification
Uses infrared spectroscopy to positively identify organic contaminants (fiber, dust, particulate, etc).

Optical clarity
Measure the light that transmits through glass containers to determine how clear the glass 
really is or if it meets the USP 660 guideline.

Thin film determination
Measure surface energy for presence of thin film contamination or abnormal droplet formation in glassware.

Mechanical testing to characterize glass supplier and lot-to-lot variations

Scratch/Abrasion Resistance
A scratch tip pen varies force setting for scratch resistance testing. A shaker table is used to shake 8 vials together for a set time and frequency and imaged for markings.

Ultimate Break Force
An Instron universal tester compresses glassware both vertically and horizontally  and records the highest applied force before breaking.

Break-Loose/ Glide Force Testing
An Instron universal tester compresses a syringe plunger in a syringe and records  the force required to move it. Attachment purchased, but testing yet to occur.

CoF (Coefficient of Friction) Testing
A friction tester varies speed and load of vial-to-vial testing to determine static 
and kinetic coefficients of friction. Imaging is performed to check the ensuing wear.

Fracture Analysis
Uses high resolution optical microscope to determine crack or break point of origin and root cause.

Parenteral packaging qualifications to identify glass packaging interactions with drug product

ICH-Q3D / USP 232
Qualifies drug product and packaging to be under acceptable limit thresholds for 24 heavy metals of concern.

Glass Extractables (Si, B, Al, Ca, Mg, K, Na)
Detects glass interactions of drug product or other solutions. Used to understand glass durability for a variety of conditions including delamination. Concentrations measured.

Accelerated Aging
Environmental control chambers or autoclave used to tightly control temperature and humidity 
for vials for glass accelerated aging studies.

Delamination-based studies to identify glass packaging interactions with drug product

High Resolution Imaging
Uses high resolution SEM imaging (x500-x5000 mag) to characterizing tubular vial pitting, 
glass delamination sites, and/or glass corrosion sites.

USP 1660 Glass Extractable Testing
Official screening method to detect propensity towards delamination between lots, glass manufacturers, 
or drug products.

USP 790 Visual Inspection
USP method for identifying visible glass particles / lamellae for glass delamination.