Packaging experimental drugs for clinical trials may well be the ultimate test for fast-changeover equipment. By their very nature, clinical trial packaging runs are short and changes frequent. Typical is the clinical trial packaging operation at the headquarters campus of pharmaceutical giant Glaxo Wellcome Inc. in Research Triangle Park, NC. Here the firm fills bottles with solid-dose medication for studies that typically call for only 700 to 1ꯠ bottles for a given trial. Tablet counts per bottle vary widely, from 210 per container to as few as one, and anything in between. And new products are added all the time. Tablet sizes and shapes vary too, from 2 mm long and 5 mm in dia to 8 mm wide and 19 mm long. It's a variance too great to permit the use of that old pharmaceutical standby, the slat counter. "We'd need a warehouse full of slats," says Dean Kazan, supervisor, clinical supplies primary packaging. New line installed Upgrading from slower, less flexible equipment, Glaxo Wellcome installed a completely new clinical trial packaging line during the summer of '94. The heart of the system, the counter/filler, was provided by DT Kalish (Somerville, NJ). (Formerly H.G. Kalish, the company is now part of DT Industries.) Kalish markets a state-of-the-art counter from sister company DT Swiftpack that uses eight infrared LED emitter/receiver sensors per lane to detect and count tablets as they pass. Twelve lanes on the filler greatly increase throughput compared to the previous machine. Glaxo Wellcome runs the counter at speeds of 40 to 55 bottles/min, which is quite fast for a clinical trial line, Kazan says. The speed boost paid off for Glaxo Wellcome's new AIDS drug, 3TC, which required numerous production runs of 18ꯠ bottles each to meet worldwide demand. In contrast, the typical run for a clinical trial is around 1ꯠ. "We ran mostly 3TC the majority of the first year and the line pretty much paid for itself," says Kazan. Another benefit is that Glaxo Wellcome is now able to fill small counts by machine. Machine capability limitations on the old counter forced packaging personnel to fill small counts by hand. That required a subsequent time-consuming inspection process. As a result, an automated 3ꯠ-bottle run of one tablet per bottle now takes one hour versus 24 hours by hand, according to Kazan. Perhaps the biggest benefit comes in fast changeover: The entire line can change in about an hour with two people versus a day and half before. The counter itself requires no physical changeover. It needs only a 15-minute cleaning between runs. There are no dedicated change parts and no tools needed to disassemble the machine. Instead, quick-release fasteners facilitate easy cleaning of about 10 components, versus 60 previously. After cleaning, a new product code is entered on the control panel, and the machine is ready to go. Glaxco Wellcome is using four bottle sizes--30, 60, 80 and 150 cc--but is currently phasing out the first two. They're being replaced by the company's patented Cameo® bottle, which consists of an outer 80-cc shell with 30-cc insert, and which further reduces the need for changeover (see sidebar). Tablet separation is key At the start of a production run, bulk tablets are dumped into a hopper of the counter, which then dribbles a flow of tablets onto a series of three cascading vibratory feed trays. These trays, which have 12 distinct lanes, vibrate the tablets so that they're single-filed in each lane by the time they reach the infrared emitter/receivers. "The key to good electronic counting is to send one tablet at a time over that eye," says Kazan. As tablets reach the end of the third tray, they vibrate right over the edge--one at a time--into twelve large cavities in the counting block. Eight LED emitter/ receiver sensors create a sort of invisible light curtain across the cavity's opening. As tablets pass and break the light curtain, the counter's microprocessor counts them. Once a predetermined number is in each cavity--typically two to six--tablets are released into a common spout that funnels tablets via gravity into the waiting bottle below. Behind those infrared emitters/ receivers is a fast microprocessor that scans the opening of the cavity 2ꯠ times per second, easily and accurately measuring how many milliseconds it takes for a tablet to break the beams. Adding to the thoroughness of tablet scanning is the orientation of the emitter beams. Every few cycles, the beams, which normally aim directly across the opening, aim diagonally left then right to adjacent emitters. They weave a tighter sensing web for more reliable tablet detection. Glaxo Wellcome sets minimum and maximum sensing times for each product, enabling the counter to distinguish two touching or overlapping tablets trying to pass as one long tablet. Unlike other counters Kazan looked at, the emitter/receivers are able to detect clear gelcaps without difficulty, as well as half-opaque/half-clear capsules that contain powdered doses. 100% accountability To establish a filling speed at which Glaxo Wellcome's 100% accuracy target can be maintained, Kazan's team first validates the counter by setting and testing the machine's parameters for each product and count. Once 200 bottles are filled with 100% accuracy, those parameters are permanently stored as a part of that product recipe. Regarding accuracy, Kazan says that the machine may give an overcount, but there's no way it will give an undercount, since the count isn't incremented unless a tablet breaks the sensing beams. In the rare event of an overcount, the counter will shut itself down and display an error code. Though the machine will fill 65 bottles/min, Glaxo Wellcome typically fills anywhere from 40 to 55/min to provide an extra margin of accuracy. "We'll sacrifice speed for accountability," Kazan explains. Even with the line's high filling accuracy, Glaxo Wellcome's procedures dictate that line personnel perform periodic in-process counts. In-process counts are accomplished by dumping the contents of a randomly sampled bottle into the smaller Swiftcount counter, which is about the size of a toaster. It vibrates tablets through two lanes, each containing eight LED emitter/receiver sensors like the larger Swiftpack. The count is displayed on the unit's digital readout. The smaller Swiftcount also doubles as a secondary filler, used for small runs consisting of 500 bottles or fewer, since it requires no changeover. Cleaning between products takes just five minutes compared to 15 or 20 for the larger Swiftpack. The smaller Swiftcount is on a mobile stand and has a quick-disconnect feature that makes it easy to integrate into the packaging line. However, the Swiftcount is not meant for high speeds, topping out at 20 bottles/min. Kazan is pleased with the changeover flexibility of the packaging operation, especially compared to what he's seen elsewhere. "We've been to numerous companies to see their packaging lines, and nobody has near the flexibility or has given it the forethought we have," he says.
