By Agnes Shanley, Editor in ChiefAs the move to increasingly selective—and potent—formulations continues (see Pharmaceutical Manufacturing, July/August, p. 45), drug manufacturers are looking for new ways to protect operators from exposure to extremely potent ingredients while maintaining production efficiency. Traditionally, workers have been shielded by personnel protective equipment (PPE), such as uncomfortable “space suits” that take time to put on and remove. The limitations of traditional PPE meant that operators could only spend a certain number of hours in the potent ingredient processing area. In addition, equipment cleaning often required changeovers with lengthy downtime. The U.S. Occupational Health and Safety Admin. (OSHA) has already challenged companies to “design in” safety, rather than relying on PPE for containment. Without waiting for legal dictates, many drug companies are taking the initiative, and, for the most potent compounds, some have lowered their acceptable occupational exposure limits (OELs) from micrograms to nanograms per cubic meter of air.
Contained filling systems that integrate isolators and filling equipment are gaining in popularity. Shown here, a system developed by Bosch Packaging Technology.
Helping them achieve these goals are customized tableting, filling and mixing systems with integral isolators—-some have been designed to be washed in place. With integrated systems, users can increase uptime and improve productivity in their operations, says John Kirk, vice president of liquid pharmaceuticals at Bosch Packaging Technology (Minneapolis). “When equipment and barrier design are approached separately, manufacturers have the expensive challenge of mating two unrelated systems, with different structural, mechanical and control issues,” he says. Bosch began to offer integrated contained filling systems in the 1990s, when it acquired TL Systems, which had pioneered work in this area. The company’s integrated contained filling systems boast a vertical wall isolator design with a narrow profile that is said to ease cleaning.Integrated systems are also becoming more important in tableting operations. “We have one integrated tableting project pending,” says Paul Olson, vice president of sales at La Calhène (Rush City, Minn.), which handles integrated system projects ranging from aseptic filling to containment from mills, granulators and dryers. “Every project is new and distinct, and customization is the rule,” he says. WIP Tableting Systems IntegratedFette America (Rockaway, N.J.) became interested in integrated containment for its wash-in-place (WIP) tableting system when it perceived the industry’s growing need for systems to handle potent compounds. The company, whose WIP systems can be tailored to various containment requirements, has designed a new integrated tablet system capable of producing 300,000 tablets per hour, which is now being installed at a pharmaceutical manufacturing plant in Puerto Rico. The new equipment, Fette’s “most contained” to date, according to operations director Sean Scully, is scheduled to come on line during the fourth quarter of this year. Fette designed most of the system in-house, down to the isolators and dust-collection units, and incorporated technology that it acquired last July when it bought the German containment and dust-collection specialist, Absolut Filtertechnik, to form Fette Absolut GmbH. The independent testing firm, Broadspire (Lake Zurich, Ill.), recently “surrogate tested” an equivalent installation, involving Fette’s 2090 Wash-in-Place tablet press, a Glatt containment valve, and isolators from Carlisle for dedusting, metal- and tablet-check components, at Fette’s facilities in New Jersey. For the test, airborne levels of Naproxen Sodium were monitored continuously for 10 hours. High ContainmentTests found that the contained system resulted in operator exposure levels of under 0.7 ng/m3 (TWA), well below the facility’s previous OEL criteria. A general air sample collected at the tablet press isolator after WIP found levels to be below the analytical limit of detection or 8.1 ng/m3.
Helping them achieve these goals are customized tableting, filling and mixing systems with integral isolators—-some have been designed to be washed in place. With integrated systems, users can increase uptime and improve productivity in their operations, says John Kirk, vice president of liquid pharmaceuticals at Bosch Packaging Technology (Minneapolis). “When equipment and barrier design are approached separately, manufacturers have the expensive challenge of mating two unrelated systems, with different structural, mechanical and control issues,” he says. Bosch began to offer integrated contained filling systems in the 1990s, when it acquired TL Systems, which had pioneered work in this area. The company’s integrated contained filling systems boast a vertical wall isolator design with a narrow profile that is said to ease cleaning.Integrated systems are also becoming more important in tableting operations. “We have one integrated tableting project pending,” says Paul Olson, vice president of sales at La Calhène (Rush City, Minn.), which handles integrated system projects ranging from aseptic filling to containment from mills, granulators and dryers. “Every project is new and distinct, and customization is the rule,” he says. WIP Tableting Systems IntegratedFette America (Rockaway, N.J.) became interested in integrated containment for its wash-in-place (WIP) tableting system when it perceived the industry’s growing need for systems to handle potent compounds. The company, whose WIP systems can be tailored to various containment requirements, has designed a new integrated tablet system capable of producing 300,000 tablets per hour, which is now being installed at a pharmaceutical manufacturing plant in Puerto Rico. The new equipment, Fette’s “most contained” to date, according to operations director Sean Scully, is scheduled to come on line during the fourth quarter of this year. Fette designed most of the system in-house, down to the isolators and dust-collection units, and incorporated technology that it acquired last July when it bought the German containment and dust-collection specialist, Absolut Filtertechnik, to form Fette Absolut GmbH. The independent testing firm, Broadspire (Lake Zurich, Ill.), recently “surrogate tested” an equivalent installation, involving Fette’s 2090 Wash-in-Place tablet press, a Glatt containment valve, and isolators from Carlisle for dedusting, metal- and tablet-check components, at Fette’s facilities in New Jersey. For the test, airborne levels of Naproxen Sodium were monitored continuously for 10 hours. High ContainmentTests found that the contained system resulted in operator exposure levels of under 0.7 ng/m3 (TWA), well below the facility’s previous OEL criteria. A general air sample collected at the tablet press isolator after WIP found levels to be below the analytical limit of detection or 8.1 ng/m3.
Shown here, an isolator integrated with a freeze dryer. Photo courtesy of La Calhène.These data indicate that the integrated systems offer effective containment, while eliminating gowning time and costs, shortening changeovers and extending the amount of time that operators can work in potent ingredient facilities. The installation posed significant design challenges, says Fette’s Operations Director Scully. First, multiple pieces of equipment from different vendors were involved, as well as different control and WIP systems. All partners risked ending up with a cumbersome installation with multiple interfaces. Project partners considered user requirements, worst case scenarios and "what if"s during the design stage. User-friendliness guided their work, Scully points out. “We wanted to make people comfortable with the equipment,” says Erik Barman, special projects manager. Where to Put the Ports?One challenge was optimizing the location of glove and rapid transfer ports—-no small feat, since human operators come in all heights and sizes. “We did a mockup, cutting out positions for glove and glove ports into Plexiglas, and mounting gloves. We then had operators put their hands in them to ensure that they could reach comfortably. This allowed us to determine optimum position height and angles,” Scully says. WIP capability was critical for this installation, so the system was designed to allow users to dispense detergents right from its central WIP system. The end-user required two isolators—-one for dedusting and metal check, the other for in-process weigh check systems. The first isolator could be washed down, the second couldn’t. Fette worked closely with the equipment vendors and developed a single isolator that could handle both dedusting and metal checking and be washed down. In addition, the firm developed a centralized system so that the containment valve could be washed along with the overall system and controlled via one operator interface. Controls were also integrated into one central control system, and alarms were designed to provide diagnostics, alerting operators to potential sources of the problem. Cradle-to-Grave Approach to DustDesign also took into account the potential hazards of dust after it has been collected. Often, pharmaceutical companies merely move bags of potent compound dust from manufacturing to maintenance areas, endangering mechanics, who don’t normally wear PPE, says Barman. The Fette system instead incorporated a dual HEPA filter designed by Absolut. Users unsnap a lid to remove the liner bags via the RTP, and the dust is housed in a double bag-in-bag container that minimizes exposure. The system has undergone extensive FAT in Germany and New Jersey. Fette has also incorporated NIR into the enclosed system for quality monitoring, and will release its new product commercially this month.
