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Early adopters of continuous manufacturing approaches shared their plans and some of their experiences at the 11th annual Charles Jarowski Symposium in Industrial Pharmacy.
Early adopters of continuous manufacturing approaches shared their plans and some of their experiences at the 11th annual Charles Jarowski Symposium in Industrial Pharmacy on May 6, 2019, at St. John’s University in New York City. Takeda Pharmaceuticals, which acquired Shire Pharma’s continuous manufacturing expertise when it bought the company, has continued continuous research and piloting efforts begun by Shire in 2016, according to Jim Bonner, Takeda’s director of small-molecule drug product, who spoke in the program (1). The company, along with Thermo Fisher’s Patheon, is exploring the use of continuous manufacturing for encapsulation as well as tableting, focusing on the continuous direct encapsulation of Vyvanse (lisdexamfetamine dimesylate), a treatment for attention deficit/hyperactivity disorder that was approved in 2007. Configuring encapsulation equipment for continuous manufacturing has been challenging, he noted.
The company has completed trial runs using near-infrared (NIR) and Raman spectroscopy, which involved scanning 30 different blends three times, then using product of least squares-based chemometric methods on reference gravimetric rather than high-performance liquid chromatography assay data. Extensive design of experiments work has also been done, and the company is anticipating approval of the continuous process by 2020. As Bonner pointed out, these efforts have underscored the need for more robust and economic process analytial technology options and simplified model maintenance. In addition, he believes that FDA should be shown that loss-in-weight feedback data are more accurate than data provided by NIR models.
Andrew Farrington, principal scientist for oral formulation sciences at Merck in West Point, PA, discussed the company’s pilot project, designed to build upon existing expertise in real-time release testing, raw materials monitoring, and quality by design (2). The pilot applies continuous-to-direct compression and film coating using tablet transmission NIR and tablet weighing instead of content uniformity, and hardness and disintegration instead of dissolution. The goals are to produce nearly one billion tablets per year with less than 90-day lead times from formulation to patient in a two-floor installation that is roughly one-third the size of traditional tableting facilities.
The company engaged early in discussions with regulators and is now working on both a continuous product development line, capable of manufacturing 5–20 kg/h of product, and a commercial line, with capacity of 10–90 kg/h. The advantages of the small-scale unit, he said, included a single point of control, facilitating remote equipment operation and potentially allowing operators to be removed from the processing environment. The company has developed a predictive model based on material attributes for continuous feeding and has also tested twin screw granulation. Although the company is optimistic about the role that continuous processes will play in the future, Farrington asserted that a mix of batch and continuous will be better for the industry’s assets and supply chains.
1. J. Bonner, “Continuous Manufacturing Challenges to Commercialization” a presentation made at the 11th annual Charles I. Jarowski Symposium in Industrial Pharmacy, May 6, 2019.
2. A. Farrington, “Challenges with Continuous Manufacturing: Integrated Development Strategy for Continuous Manufacturing of Oral Drug Products,” a presentation made at the 11th annual Charles I. Jarowski Symposium in Industrial Pharmacy, May 6, 2019.
Vol. 43, No. 9
When referring to this article, please cite it as A. Shanley, "Industry Experiences in Continuous Manufacturing for Encapsulation and Tableting," Pharmaceutical Technology 43 (9) 2019.