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FDA funded projects at Rutgers' C-SOPS and at UMass Lowell to develop flow-sheet model algorithms for use in risk assessment, and start-up company Continuus Pharmaceuticals is making progress on their integrated system.
With progress being made in continuous manufacturing of solid-dosage drug products, there is an increasing need for tools to aid risk assessment. In August 2014, FDA awarded a $0.5 million grant to the Engineering Research Center for Structured Organic Particulate Systems (C-SOPS) at Rutgers University and another $0.5 million grant to the University of Massachusetts, Lowell (UML) for the development of process simulation and modeling tools for integrated solid-dosage drug manufacturing processes, and work is now underway. The tools will be used for risk assessment of continuous pharmaceutical manufacturing processes, for control strategies, and to identify critical material attributes and process parameters. Continuus Pharmaceuticals, a spin-off company that launched from the Novartis–Massachusetts Institute of Technology (MIT) Center for Continuous Manufacturing, is taking a different approach and is developing an end-to-end integrated continuous manufacturing process for pharmaceutical products.
University of Massachusetts, Lowell
Dr. Seongkyu Yoon, assistant professor in the Chemical Engineering department at UML, is the head of UML's three-year project, which is the university's first project to receive official funding from FDA. The goals of the project are to develop and provide training for process models and a simulation platform, to conduct case studies for quality risk assessment and control strategy determination, and to conduct verification and validation of process models by comparing model predictions with experimental data, reported UML in a press release. Dr. Yoon also leads the Biopharmaceutical Process and Quality Consortium (BPQC) based in the Massachusetts BioManufacturing Center at UML. The BPQC has been working on continuous biopharmaceutical process design and modeling and quality by design and process analytical technology for risk assessment and control strategy determination. The solid-dosage modeling project, which will use the same engineering principles, will be an extension of this research work, notes Dr. Yoon.
The multiyear project at C-SOPS is focusing on developing flow sheet-model algorithms that dynamically simulate an integrated process from individually developed unit operation models. FDA plans to use these models in the future for risk assessment of process submissions, including failure mode analysis in continuous drug product pharmaceutical manufacturing.
C-SOPS has been working on several projects associated with continuous solid-dosage manufacturing since 2006. At the biannual C-SOPS advisory board meeting in College Park, Maryland on Oct. 29–30, 2014, C-SOPS researchers from Rutgers University, Purdue University, the New Jersey Institute of Technology, and the University of Puerto Rico reported progress on projects and obtained feedback from the C-SOPS industrial consortium, which includes more than 45 companies. Dr. Lawrence X. Yu, acting director of the Office of Pharmaceutical Science at FDA, was the keynote speaker at the meeting. Dr. Yu commended the Center for helping to enable FDA’s vision of the future of pharmaceutical solid-dosage manufacturing in the area of continuous processes, reported Doug Hausner, associate director for Industrial Relations and Business Development at C-SOPS. Dr. Yu further challenged the team to tackle the existing scientific challenges related to pharmaceutical batch manufacturing, indicating that the transition to continuous will take time and many of the scientific approaches used to develop continuous manufacturing are applicable to the challenges that plague batch manufacturing.
The project team at the Novartis–MIT Center for Continuous Manufacturing successfully demonstrated proof-of-concept of its Integrated Continuous Manufacturing (ICM) technology that combines the synthesis of API and final solid-dosage form in a seamless process, and the technology was transferred in 2012 to Novartis, where development is progressing internally. Continuus Pharmaceuticals was launched in 2013 to apply ICM to the broader pharmaceutical industry, and the company has an exclusive license with MIT that is co-exclusive with Novartis. The start-up company has raised $2.5 million in the past two years, notes founder and CEO, Salvatore Mascia, who was formerly the project manager of the Novartis–MIT Center. Earlier in 2014, the company partnered with pharmaceutical equipment manufacturer IMA Industria Macchine Automatiche, and in November, Continuus announced an alliance with New England Controls, a business of Emerson. In December 2014, Continuus moved into its new process development facility in Woburn, Massachusetts, and the company is ready to begin process development work with clients who want to investigate its novel ICM technology. "We have a pilot process and are ready to go to the next level," says Mascia. He notes that the novel process technology will require a change in operational structure and mindset, but offers significant advantages in efficiency by eliminating the corrective steps required in existing solid-dosage manufacturing. Mascia says that the concept has high-level FDA support.