Study: Automatic Inspection for Lyophilized Drug Products in Valor Vials

Companies partnered to test whether the new vial material would present obstacles to proper inspection for pharmaceutical manufacturers.

While material developments can be exciting and full of possibility, the reality is that sticking with what works—and what’s validated—is a very tempting proposition for pharma manufacturers who question whether existing machinery will work with the new innovation.

With Corning’s new Valor Glass, the company set out to ensure that its new technology could exist as a “drop-in” solution, capable of being incorporated into production lines without replacing current machinery or necessitating significant augmentations.

First, what is Valor Glass? Glass tech has largely remained the same for the last century, but Corning has developed a glass for vials that is more resistant to damage than conventional glass and with a low coefficient of friction exterior coating. This is important because:

  • Pharmaceutical filling lines process hundreds of conventional borosilicate vials a minute, creating glass-to-glass contact that can lead to scratches and breakage.
  • In addition to causing waste, this frictive contact can generate small glass particles that necessitate cleaning, resulting in costly manufacturing downtime.
  • Conventional borosilicate glass vials have a high coefficient of friction surface, increasing their predisposition to jam. In this situation, operators may have to intervene, increasing the potential for contamination. 

With a “Quality by Design” approach, Corning’s Valor vial was specifically developed as a drop-in glass packaging solution that minimizes many of these challenges. For example, Corning identified and solved for the root cause of delamination by developing a new glass composition that still meets the USP hydrolytic requirements for Type I pharmaceutical glass. In addition, Corning applied chemical strengthening that the company reports improves breakage resistance and provides at least 30x protection against stable crack formation in laboratory testing.

Testing needed to be performed to confirm that Valor Glass’ patented exterior coating would not affect the lighting and performance of automatic inspection machines (AIM). AIMs are utilized by numerous pharmaceutical companies throughout the world and are a key component to consistent and efficient inspections that improve output and reduce false rejects. Automated inspection machines require substantial investment, so retrofitting or replacing them might cause manufacturers to pause and consider financial implications before incorporating any new vial, regardless of the container’s advantages.

Inspection testing

Corning approached Antares Vision, a global provider of inspection technology, and inquired whether the company could provide a machine capable of inspecting its new Valor vials, and determining what effects, if any, the containers would have on inspection performance. Antares worked with Corning to create filled Valor vials with defects similar to those found in pharmaceutical operations for lyophilized drug products. Then inspection was performed for both product and container defects utilizing the Antares Vision Lyo-check automated inspection machine.

Inspection was performed for both product and container defects utilizing the Antares Vision Lyo-check automated inspection machine.Inspection was performed for both product and container defects utilizing the Antares Vision Lyo-check automated inspection machine.The purpose of this study was to determine the effect of the Valor vial exterior coating on the challenging automated inspection of lyophilized drug defects–particularly regarding lighting and vision requirements. Lyophilized products are deemed difficult to inspect due to variations in the quality and consistency of the “lyo cake,” and the ability of particles to hide within the dried powder; a lack of contrast adds to imaging challenges. 

  • To minimize dimensional variability influence, Corning provided sized, matched, coated and uncoated small vials. The study was set up so that a sample set of “Good Vials” (coated and uncoated) was created with lyophilized product inside, with “no defects” present in the vial, stopper, crimp or lyophilized cake;
  • A second set of “Defect Vials” was also created with lyophilized product containing the various lists of defects found in Table 1. Inspections consisted of typical methods performed in a pharmaceutical automated environment, at speeds up to 24,000 pcs/hour. The study was designed to determine if automated inspections are affected by the glass composition or coating on the vials.  

Inspection station setup description.Inspection station setup description.

After creating the product and adding the specific defects, each sample was rubber stoppered under vacuum and an aluminum crimp applied with cap, consistent with the quality deemed acceptable for typical sterile processing and capping operations for pharmaceutical manufacturers. As closely as possible, these samples and inspections were meant to align with automated inspections for GMP operations within an FDA regulated environment. All defects were quantitatively and qualitatively known and recorded prior to inspection to verify their ability to be identified with regularity and consistency in an automated inspection machine. Antares Vision performed this testing in a new Horizon 2020 combination Lyo/Liquid VRI (Visual Rotating Inspection) machine, collecting all data regarding inspection cameras, lighting, and software inspection tools.

Creation of defects

A group of 40 Valor vials, along with stoppers, were shipped to a third party specializing in creating realistic lyophilized products for inspection testing. This third party filled the vials to 1/3 of the volume and developed a formulation that fulfills all requirements of a stable lyo cake for long-term routine usage. The formulation was chosen to be very stable and resistant to the mechanical stresses found in manufacturing, so that the end-user may re-use the samples many times as challenge test kits, training manuals for inspectors or as part of validation runs, to name a few examples.

The third-party developer also created cosmetic defects in the glass, including scratches and chips to precise measurements. Test protocols typically call for cracks in the glass to be created and tested to see if they can be imaged. However, due to the unique nature and properties of Valor Glass, the energy required to crack the glass resulted in full breakage (by design) of the vial structure; therefore, a cracked Valor vial was not an issue considered during our inspection testing.

Inspection machine specifications at a glance

  • 18 different inspection points with unique camera and lighting design, including boomerang arms to capture more images
  • Electrical cabinet and control cabinet with HMI touch screen
  • Various reject stations including one for AQL Sample
  • Floating Carousel design to allow easy clean-up of spillage and broken glass
  • Head Space Gas Analysis or optional Vacuum Leak test
  • Loading can be performed manually, directly from trays

Starwheels, guides, and changeover

  • Handling of glass vials is smoothly performed by a minimum of screws, star wheels, and guides made of high-density POM-C
  • Star wheels and screws are driven by a brushless motor electrically geared with the carousel motor
  • Changeover for different container sizes can be done in 30 minutes without the need of any special tool

Inspection station optical set-ups

Five inspection stations on the Lyo-Check were set up, encompassing inspection from above, bottom, and side, in addition to neck/shoulder and heel. (Set-up details of each of the five can be found in the images—scroll through at top of page). All lights are LED strobes.

Screen Shot 2020 08 10 At 4 57 22 Pm

Test setup for the machine

For the best comparison, identical optical setup was used to run both sample sets: the same intensity of light in back and front lighting and the same camera settings (gain, exposure time). As the companies report, “A concern with any coating is light scattering or anomalous light reflections due to the different types of glass/coatings that can have negative impacts on the rate of defect detection. In this case, the machine was set up based on the uncoated glass to create a format for that product. After the uncoated set was run, there was no change to the system parameters and the coated Valor vial sample set was run. Images of both sets were collected, and the results were compared.”

Key takeaways

  • The study found there were no significant differences in detecting similar defects in the two test kits, affirming that the same machine setup can be used for dimensionally matched uncoated and coated vials, and no light scattering or anomalous light reflection was observed due to the coating of Valor vials.
  • The Valor vial coating only appears in backlighting (a seldom-used detection technology) when compared to the uncoated glass, which may slightly reduce the sensitivity of the system where contrast of defects is small. If running only Valor Glass, the system parameters can be adjusted to give the maximum contrast for that product.
  • The study confirmed there is potential for both uncoated and coated vials to be run with the same machine setup with identical performance. The sample images and quantitative histograms of mean grey levels of lighting below show that the slight decrease in brightness (~15%) for the coated vial (left) over the uncoated vial (right) should not affect the sensitivity of defect detection.

Sample images and quantitative histograms of mean grey levels of lighting show that the slight decrease in brightness (~15%) for the coated vial (left) over the uncoated vial (right) should not affect the sensitivity of defect detection.Sample images and quantitative histograms of mean grey levels of lighting show that the slight decrease in brightness (~15%) for the coated vial (left) over the uncoated vial (right) should not affect the sensitivity of defect detection.

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