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Progress in equipment availability, process analytical technology, and advanced process control aids ongoing development of continuous solid-dosage manufacturing processes.
Progress in continuous manufacturing for solid-dosage drugs was evident at INTERPHEX 2014, held March 18–20 in New York City. Equipment manufacturers now offer continuous lines, such as the Lodige Granucon continuous granulation and drying system and the GEA ConsiGma system that includes a high-shear granulator, dryer, in-line blender, and tablet press. Most recently, at interpack 2014, Glatt introduced the MODCOS continuous rotary chamber process insert, which can be used to convert Glatt ’s batch GPCG to a continuous fluidized-bed system. Associated equipment for continuous process lines, such as feeders, control systems, and process analytical technology (PAT), are also now available from several companies.
“We have seen a huge increase in the amount of interest since last year’s INTERPHEX,” said Doug Hausner, associate director for industrial relations and business development with the Engineering Research Center for Structured Organic Particulate Systems (C-SOPS) based at Rutgers University in New Jersey, in an interview with Pharmaceutical Technology. FDA has actively promoted use of continuous processes, and a number of applications using continuous processes are currently in review by the agency. Approval and commercial production of these products is expected to give a boost to the adoption of continuous processing technology by the rest of the industry, noted Hausner.
Hot-melt extrusion (HME) is one type of continuous processing technology that has been embraced over the past decade, noted Charlie Martin, president of Leistritz, in an interview with Pharmaceutical Technology. HME is a “battle-hardened,” proven technology that has been used for 50 years in other industries. The challenge for the pharmaceutical industry is to learn this existing technology and apply its well-known processing principles to pharmaceutical processes, said Martin. One opportunity for industry members to learn more about HME is an annual Pharmaceutical Extrusion Seminar sponsored by Leistritz, to be held on June 18-19, 2014.
One of the initial drivers for interest in continuous pharmaceutical processing was FDA’s PAT initiative. Integration of PAT into continuous lines is an ongoing focus of research and development. “Upcoming technologies will have a real effect on what can be done in terms of real-time measurement,” predicts Hausner.
Another area of development is integrating advanced control of processes, which is of interest to regulatory agencies because it can lead to greater control and thus improved quality. Advanced control moves beyond local control of individual unit operations and incorporates an overall supervisory control system. In an advanced process control solution, data from PAT is captured in a PAT or quality-management system, explained Pamela Bruen Docherty, Life Sciences industry manager USA at Siemens, in a presentation at INTERPHEX 2014. “In a continuous process, the data comes quickly and you want to react to it quickly,” said Docherty. “A solution must capture and interpret the data in real-time to adjust the process parameters and keep the product within control.” The goal is to manage the data and allow real-time release of the product.
Some question how a batch can be defined when using a continuous process. “According to FDA regulations, a batch is an amount, not the manufacturing method,” explained Docherty in the presentation. A batch is defined as a specific amount produced in a unit of time (e.g., a day) or quantity (e.g., kilograms or a tablet count) that has uniform characteristics within specified limits. The batch definition should allow traceability in case of a recall.
One of the current needs is to develop better business models and design effective tools to measure return on investment for continuous processing, because it is quite different from existing batch processes, noted Hausner in a presentation at INTERPHEX 2014. With many aspects of continuous manufacturing in active development, further progress can be expected in the upcoming year.