| Abstrakt: |
Background: For pharmaceutical products, an in-depth understanding of manufacturing processes and quality risks associated with quality by design (QbD) development enables the production of high-quality products. Product recall due to quality issues could be minimized for QbD-developed products. Furthermore, the review period instituted by regulatory authorities could be shortened by allowing reviewers to access technical documents with QbD elements. The aim of this study was to examine the impact of QbD development from the viewpoints of regulatory flexibility, product quality related to recall, and review period in Pharmaceuticals and Medical Devices Agency (PMDA) in Japan. Methods: QbD developments for new active ingredients, approved from 2009 to 2018, were surveyed in the PMDA review reports, and review periods were investigated on the PMDA website. Voluntary product recalls and their rationale were investigated using the website of the Japan Ministry of Health, Labour and Welfare. Results: Although the developmental ratio with QbD elements was increased from 9% in 2009 to 71% in 2018, the development of design space for drug substances and products between 2009 and 2018 was only 2%, and real time release testing (RTRT) for drug products was limited to 3%. Voluntary recall and extension of the review period for QbD-developed products were not observed. Conclusion: The advantages of systematic QbD development were suggested for no voluntary recall of QbD-developed products. Conversely, applicants did not actively seek regulatory flexibility with design space or RTRT, and QbD development failed to impact the PMDA review period. |
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