The benefits of continuous manufacturing of solid-dosage drugs are beginning to be realized.
Continuous manufacturing is beginning to be used commercially to produce traditional tablets. In March 2016, Hovione announced that it would install a commercial-scale continuous solid-dosage manufacturing facility as part of an agreement with Vertex Pharmaceuticals. And in April, Janssen Supply Chain announced FDA approval for using continuous manufacturing to make its PREZISTA (darunavir) 600 mg tablets in its Gurabo, Puerto Rico facility. This approval was the result of years of development, which included building a full-scale test line at the Engineering Research Center for Structured Organic Particulate Systems (C-SOPS) based at the Rutgers University School of Engineering, as described in a Rutgers press release.
At INTERPHEX 2016, Doug Hausner, Associate Director for Industrial Relations and Business Development at C-SOPS, described the advantages of being able to do more rapid process development using continuous manufacturing. Using continuous manufacturing, points in a design of experiments can be performed in minutes rather than days and use significantly less API. Rapid development can help companies improve speed to market, noted Hausner. Continuous manfuacturing is still not broadly understood, which is a roadblock to greater adoption, but upcoming training programs aim to increase industry exposure.
FDA has expressed support for continuous manufacturing, and in 2015, FDA awarded $4.9 million in grant funding, administered by the National Institutes of Health (NIH), to C-SOPS institutions. Part of this grant is going to the New Jersey Institute of Technology (NJIT), a C-SOPS partner institution, to support the development of regulatory science for continuous manufacturing of strip-film based drug-dosage forms capable of real-time release. Rajesh N. Davé, professor at NJIT and the project's leader, spoke at INTERPHEX 2016 about the thin-film technology. He demonstrated that film technology can be used for poorly soluble APIs by using particle engineering and embedding particles in the film matrix using slurry casting instead of the conventional solvent casting. Davé also showed how process analytical technology, such as Raman or near infrared spectroscopy, can be used to monitor drug content and film thickness.
Arjun Giridhar, staff scientist at Purdue University, which is another C-SOPS partner institution, also spoke at INTERPHEX 2016. He described a different processing technology-drop-wise additive manufacturing of pharmaceutical products (DAMPP), which deposits a drug (in liquid drops) on a film or tablet. Using liquids has several advantages, including avoiding problems associated with powder handling. Giridhar explained the importance of depositing the drops precisely and consistently as well as precisely measuring drops. The research group has had success in consistent production with 1% or less variation.