Challenges and Strategies for Implementing Automated Visual Inspection for Biopharmaceuticals - Pharmaceutical Technology

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Challenges and Strategies for Implementing Automated Visual Inspection for Biopharmaceuticals
The authors used a light-transmission-based static division system to detect particles of foreign contaminants in prefilled vials.

Pharmaceutical Technology

Results and discussion

Systematic studies were conducted to evaluate the effect of key process parameters, including machine settings, product properties, and fill configuration on the performance of the AVI system.

Table I: List of machine parameters potentially impacting detection rates.
Role of machine parameters. The key operating parameters for the AVI process included the machine settings used during inspection (see Table I).

Figure 1: Mechanism of visible particle detection through a static-division sensor-based AVI system. (ALL FIGURES ARE COURTESY OF THE AUTHORS)
Impact of machine sensitivity. The mechanism of operation of a SD sensor-based system involved sensing the variations in the electric signal (voltage level) as a result of light interference by foreign particles. Sensitivity of the machine refers to the threshold DC voltage signal that should be exceeded to judge the vial as faulty. A higher sensitivity would improve the machine's ability to detect foreign particles, especially those of smaller sizes as shown in Figure 2. However, there is a threshold sensitivity above which the improved detection rates come at the cost of false rejection. Even clean vials with no foreign contaminants were judged by the machine as faulty (see Figure 2). Careful selection of the sensitivity levels should be made to maximize the detection rates while minimizing the business costs associated with rejection of nondefective vials.

Figure 2: Comparison of detection rates for particles of different sizes when using two different levels of sensitivity (Formulation A). The impact of sensitivity on detection rate for smaller particles is larger and higher sensitivity may result in false rejects (i.e., rejection of clean vials).
Impact of spin speed and brake position. The key requirement for tuning the ability of the machine to detect particles was to adjust the balance between the vial rotation and the precise timing and position when the vial was stopped and inspected. In an optimal set-up, the liquid surface (see Figure 1) would have been completely restored right before its inspection. If the rotation of the vial is terminated too late (i.e., represented by larger brake setting here) the liquid level may not be restored at the time of inspection and the moving meniscus can send the faulty signal to the detector resulting in a false reject. On the other hand, if the rotation is terminated too early, the liquid would have slowed down and the foreign particle would have started sinking even before reaching the inspection station. This slowdown could result in the machine missing a defective vial and wrongly classifying it as an "accept." Figure 3 shows that the detection rates for all particle sizes were improved when the brake settings were increased from 7 to 9, signifying a better performance when inspection is conducted closer to the termination of rotation. Similar improvement in performance was observed when the spin speed was increased from 1600 rpm to 2200 rpm. Higher rpm rates seemed to impart larger momentum to the liquid and suspended particles and thereby keeps them moving for a longer time, making them easier to detect. The magnitude of this effect could depend on product property (e.g., viscosity) and fill configuration (e.g., container size and fill volume) as discussed in the following sections.


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