Pharmaceutical Technology - December 2019

Pharmaceutical Technology - Regulatory Sourcebook

Issue link:

Contents of this Issue


Page 15 of 43

16 Pharmaceutical Technology REGULATORY SOURCEBOOK DECEMBER 2019 P h a r mTe c h . c o m use of PAT and DoE much earlier in the process. Within the past five years, high-throughput min- iature bioreactors, which were previously used in pre-clinical screening, have been replacing bench- scale bioreactors in scale-down exercises. Scale- down is an important step in scaling up processes for current good manufacturing practices manu- facturing in late-stage clinical development. The devices eliminate the problems found with microtiter plates, spin tubes, and shake f lasks, which can be difficult to automate (1), and allow more than 24 bioreactors to be run in parallel. They are also fitted with analytics that can take continuous readings on such crucial variables as pH, dissolved oxygen, and pressure for each of many samples. Although developers have not yet filed new drug applications (NDAs) with FDA mentioning this technology, more companies including Genentech, Merck, Biogen, Lonza, and FujiFilm are working on this approach to scale-down (2). Developers are using devices such as Sartorius Stedim's ambr 15 and 250 bioreactors (3). Starting in 2015, Sarto- rius Stedim Biotech has integrated Umetrics' DoE software with its ambr 15 and 250 high throughput minibioreactors, later incorporated Nova Biomedi- cal's BioProfile FLEX2 automated cell culture ana- lyzer, to simplify PAT and QbD work, and make scaleup and process optimization more efficient (4). The approach is also being evaluated for use in gene and cell therapy development. If anything, these developments show the du- rability and importance of DoE as a way to make drug development (whether for small molecules or biopharmaceuticals) more systematic. Equipment and software evolution promises to make these techniques, as well as QbD approaches, easier to apply in the future. References 1. M. Lourdes Velez-Suberbie et al, Biotechnology Progress, 31(1) 2018, pp 58-68, PMC5836883/ 2. F. Slingsby and S. Dewar, "Use of the ambr 250 in Conjunction with High Throughput Design and Analysis Tools for Rapid, Scaleable USP development," Fujifilm White Paper, January 15, 2015. 3. V. Sandner et al, "Scale-Down Model Development in Ambr Systems: An Industrial Perspective," https://fujifilmdiosynth. com/assets/Scale-Down-Model-Development-in-ambr-systems- An-industrial-Perspective.pdf. 4. Sartorius-Stedim Biotechnology, Product Brochure, 2019. PT Design of Experiments Scale-down is an important step in scaling up processes for current good manufacturing practices manufacturing in late-stage clinical development. Visit to read the following articles about quality and process development: • AQbD, the Evolution of Pharmacopoeial Standards? • QbD Takes Shape for Topical Pharmaceuticals • Design Space Characterization and Risk Assessment Through Mechanistic Modeling and-risk-assessment-through-mechanistic-modeling • QbD and API Process Development: A Marriage of Chemistry and Engineering development-marriage-chemistry-and-engineering • Simple by Design • QbD: Improving Pharmaceutical Development and Manufacturing Workflows to Deliver Better Patient Outcomes development-and-manufacturing-workflows- deliver-better-patient-outcomes More on Quality

Articles in this issue

Links on this page

Archives of this issue

view archives of Pharmaceutical Technology - December 2019 - Pharmaceutical Technology - Regulatory Sourcebook