2. How Inspection Techniques have been transformed ?

In the past, various vision solutions for the inline inspection of syringes have been implemented, checking the presence of the parts composing the device (piston, needle,) and liquid for pre-filled syringes for instance.

As vision solutions give limited results, X-ray technic has been implemented.

X-Ray brings the advantage of providing internal information, whereas vision will often be limited by the primary packaging. It is a relevant mean of inspection for various medical devices.

Thus, InLine 2D X-ray equipment has been designed to perform inspection of injection or dispensing devices.

Yet, for some objects, the 2-dimensional approach of vision and X-ray methods cannot prevent for not seeing a defect under certain specific angles.

For example, for glass syringes, a torsion defect of the needle can be hidden if it is in the X-ray source/detector axis.

A crack can be found on a glass syringe or ampoule, but not detected when it is tangential, and parallel to the X-ray axis.

Therefore in such cases, a 3-dimensional assessment of the object is necessary. A solution is to apply and transpose Computed Tomography techniques to this inspection case so as to give more information on the inspected object.

3. What is Tomography ?

Computed Tomography imaging (X-ray CT) consists of directing X-rays onto an object from multiple orientations and measuring the decrease in intensity along a series of linear paths(1)(2)(3). A specific algorithm – a reconstruction algorithm – is then used to reconstruct the distribution of X-ray attenuation in the volume being imaged, and to create a virtual 3D representation of the object.

In the case of an inspection equipment, Computed Tomography requires to rotate the object or to have the X-ray source and the detector that turn around it.

This rotation is necessary to acquire hundreds of 2D radiographies, in order to create the 3D volume.

The implementation of Computed Tomography in a production line is thus to be considered, but remains technically complex due to the necessity of manipulating and rotating the object in a very short time, and, depending on the object to inspect, quite expensive.

Working within these constraints, CyXplus proposed to inspect a large number of units at the same time, instead of performing a tomography on a single object inline.

Despite the fact it requires a manual loading, the application is in the production process, “at-line” instead of “in-line”, where cycle time requirements are very demanding.

The inspection session is organized by batches of nests or tubs. Each batch is associated with a dedicated recipe (with its dedicated inspection parameters), and the machine inspects the tubs one after the other.

In this configuration, all the syringes present in a given tub are inspected at the same time.

Thanks to the database architecture, a production quality analysis can be done in real time. Automatic reports with statistical indicators can be generated to show a production problem.

Thanks to its ultrafast CT architecture, the CyXCT+160 is able to inspect an object of 100 cm3, with a 100μm resolution in less than 30 seconds.

In the present syringe inspection application, the CyXCT+160 system needs 80 seconds for the inspection of a nest, with 2000 controls performed and at a 100μm resolution.

Cycle time is one thing, but the accuracy of the inspection is essential. For the syringe inspection application, CyXplus has developed a dedicated defect detection module for CyXCT software. This detection module checks different type of default :

• Needle angle defect – number of defectives tests per tub.
• Cap deformation defect – number of defectives tests per tub.
• Distance needle/cap defect – number of defectives tests per tub. • Cap insert defect – number of defectives tests per tub.
• Syringe presence defect – number of defectives tests per tub.
• Needle presence defect – number of defectives tests per tub.
• Closure presence defect – number of defectives tests per tub.

The batches, objects and detection information are consolidated into 3 databases to insure the conformity with the 21 CFR Part 11(4):

• Database with control results.
• Database allowing to perform diagnostic.
• Database with alarms and events recording.

Thus, the reconstruction and signal processing algorithms enable to accurately detect, localize and quantify defects, in a cycle time compatible with value expected for a production line.
Inspection reports are saved in the database according to the 21CFR part 11 standard(4), and also in pdf format. The production reports are edited with the localization of the defective syringes for each tub.

These results show that X-Ray CT is a very interesting technique for this application (syringe inspection), due to its performance.