Quality Control Advances

Quality control requires constant attention on pharmaceutical packaging lines, but it doesn't have to cause sleepless nights for operators and managers. Today, faster and more sensitive quality-control equipment provides continuous online vigilance. Data-collection capabilities are more robust too, which increases automation of record-keeping and validation. Vendors also are providing tools to help match quality-control systems to applications. Quality-control machines, introduced in the past year or so, are indicative of the technology available today and include systems for visual inspection, leak detection/seal integrity confirmation, checkweighing, and contaminant detection.

Hallie Forcinio

Visual-inspection systems

Visual-inspection systems, such as vision sensors, smart cameras, and camera-based vision systems, confirm the presence and position of caps, lids, and labels and check for particulates, label accuracy, and surface imperfections.

For the most demanding applications, full-scale machine-vision systems provide the highest level of programming flexibility. Although machine-vision systems are still the most complex to set up and configure, software and operator interfaces streamline configuration and simplify operation.

In the mid-range of functionality and ease of use, smart cameras combine a camera with onboard intelligence and an array of software tools that offer considerable flexibility for application programming.

The simplest and easiest to implement system, the vision sensor, also combines a camera with onboard intelligence and is optimized for optical-inspection tasks. A vision sensor can be taught to compare a captured image to a good sample and/or check for specific defects. Its capabilities are sufficient for many packaging-line inspection tasks (1).

Software is designed to be intuitive even for users who are not vision experts, said Jim Anderson, product manager for machine vision at SICK, in a company publication (1) (vision sensors, smart cameras, vision systems, SICK).

For pharmaceutical packaging applications, one robot-supported inspection machine handles almost any cylindrical container with a volume between 1 mL and 100 mL, including vials, syringes, ampuls, cartridges, cylindrical blow–fill–seal containers, and inhalers. The six-axis robot arm moves up to 15 containers per minute through three machine-vision inspection stations equipped with different camera, lighting, and container positioning options. In some cases, more than one inspection is performed at a single station. The system can check for the following: particles from a bottom or side view; proper cap application; dirt or cracks at the shoulder of the container; scratches, cracks, or chips on the neck, shoulder, or sidewall; cracks at the heel; flaws on the bottom of the container or heavy particles in suspension; and particle or cosmetic defects. The compact system is compatible with isolator enclosures and particularly well-suited for toxic or highly potent products (Seidenader RIM inspector with robot arm from Stäubli Group, Körber Medipack).

Another multiple-camera, machine-vision system examines tablets from six angles to confirm surface quality. Laser-slit lighting and three-dimensional images improve identification of chips and embossing flaws, while color cameras and filters detect subtle color variations. Simulation modes shorten set-up time, and fewer, lighter change parts reduce changeover time. The system runs up to about 5800 tablets per min (Viswill TVIS-EX3-CD visual inspection system for tablets, Daiichi Jitsugyo America).

A print quality inspection and barcode verifier for thermal and thermal-transfer printed labels performs a variety of inspections. Functions include master-to-label comparison (i.e., blemish detection), one- and two-dimensional barcode verification and validation, optical character recognition, optical character verification, field matching, and number/data validation. Additionally, the software includes automatic setup for quick label and field identification, job retrieval for recall of previous runs, and a robust alarm matrix for user-defined input/output interaction with peripheral devices. The rugged design of the read head and mounting plate simplify integration with thermal label printers and other slow-speed roll printing applications. The system is 21 CFR Part 11 compliant-ready, offering multiple security levels and comprehensive data management and reporting options (LVS 7500 inspection system, Label Vision Systems).

Leak detection/seal integrity

A high-speed, vacuum-based system provides 100% inspection of prefilled syringes for leaks at up to 600 syringes per min. The patented system positions the syringe so its entire surface can be checked without altering the position of the stopper or affecting the product. (Wilcomat R 36 MC/LFC high-speed leak tester, Wilco AG).

An inspection system based on infrared technology confirms seal integrity in flexible packaging and between thermoformed trays and lidstock (see Figure 1). A high-definition infrared camera captures an image of each seal immediately after sealing. Software analyzes the image, detects any abnormality in the seal, and rejects leakers. The equipment also monitors sealer function and can provide an alert if maintenance is needed (infrared seal inspector, Qipack BVBA).

Figure 1. A seal inspector is based on infrared technology (infrared seal inspector, Qipack).

High-voltage leak detection (HVLD) finds flaws in prefilled syringes, liquid-filled vials, blow–fill–seal containers, ampuls, and liquid-filled pouches. The off-line laboratory instrument nondestructively tests container/closure integrity and locates pinholes, microcracks, and other defects as small as 1 micron. Seamless migration to production-scale systems simplifies validation of 100% inline testing (Nikka Densok E-Scan 625 HVLD micro leak detection system, PTI Inspection Systems).

Checkweighing

Checkweighing improves product quality, meets regulatory requirements, and reduces production costs, according to a downloadable guide that helps drug packagers establish a checkweighing program and covers checkweigher design features, equipment accuracy and statistical process control (2). The document also defines operating goals, total cost of ownership, and metrological regulations and guidelines while supporting installation, verification, and limit setting to maximize efficiency and minimize costs (Principles of Checkweighing Guide, Mettler-Toledo Hi-Speed).

A family of mid-range, servo-driven checkweighers measures up to 7500 g at 250 per min and features a touch-screen operator interface, a 100-recipe memory, four password-protected user levels, validation support, and an extended event log. Product transport belt changes require no tools, and a variety of reject devices are offered. High ground clearance simplifies cleaning (HC-M-WD washdown IP69K checkweigher, HC-M-VA stainless steel design IP65 checkweigher, and HC-M-MDi checkweigher/metal detector combination, OCS Checkweighers).

Contaminant detection

Today's metal detectors can locate smaller metal fragments. One system detects ferrous fragments as small as 0.25 mm with a 95 × 22 mm head. The machine is capable of checking up to 30,000 solid dosage forms per min and successfully locating metal fragments in difficult-to-inspect liquid gels or iron-containing tablets by filtering out the signal emitted by the product itself. A slightly less sensitive 95 × 38 mm head also is available (Insight PH pharmaceutical metal detector, Lock Inspection Systems).

Contaminant-detection systems with X-ray technology can "see" a wide range of foreign objects. One family of advanced X-ray detectors offers mixed product and multilane inspection and count, seal, and weight confirmation. Other features include toolless disassembly for cleaning, compact 60-in overall length, low-profile design, and auto-learn mode for easy setup. One model is shown in Figure 2 (E-Z Tec XR-Pack X-Ray detector, Eriez). One of the latest models checks upright packages and containers from the side with a side-shoot beam rather than the up-shoot beam that is standard in other models in the group (E-Z Tec XR-SS X-ray detector, Eriez).

Figure 2. An X-ray detector looks for foreign objects and checks package integrity (E-Z Tec XR-Pack X-ray detector, Eriez).

Another X-ray system detects sub-visual foreign particles in lyo cakes and suspensions in vials, ampuls, or syringes with a substantially lower false reject rate than traditional camera-based inspection systems. Detectable particle sizes include 20 microns for metal, 50 microns for glass and 90–100 microns for plastic or rubber. Capable of checking 200–400 products per min, the inline or standalone X-ray system can be integrated with modules devoted to headspace analysis and near infrared-based lyo cake moisture detection. Bubbles, which can be problematic for some inspection systems, are virtually invisible to the X-ray beam, which also can confirm proper needle alignment and check for missing stopper material or splintered glass, defects that would ordinarily be concealed by the crimp cap (Wilcomat X-Ray particle detector, Wilco AG).

Hallie Forcinio is Pharmaceutical Technology's Packaging Forum editor, 4708 Morningside Drive, Cleveland, OH 44109, tel. 216.351.5824, fax 216.351.5684, editorhal@cs.com.

References

1. J. Anderson, Easily Solve Three Common Quality Control Problems in Packaging with Vision Sensors, (SICK, Minneapolis, MN, 2012), p. 2.

2. Mettler-Toledo, Principles of Checkweighing (Mettler-Toledo, Columbus, OH, 2012).