P233: Accelerating Cell Therapy Development and Improving Quality in Manufacturing by New Regulation Framework in Taiwan
Poster Presenter
Fong-Chun Huang
Senior Bio CMC Reviewer
TFDA/Center for Drug Evaluation Taiwan
Objectives
The purpose of this study is to investigate impacts of implementing cell therapy medical technique in Taiwan on the development of cell therapy industry and the manufacturing and quality controls of cell therapy developer.
Method
1. Collected applications of cell therapy medical technique from 2019 to 2021.
2. Retrieved application information and quality issues of specific cases from CDE E-management Database.
3. Classified cases, analyzed the data and quality issues from different perspectives.
Results
There are two regulatory pathways for applying cell therapy to clinical use in Taiwan: the regulation of cell therapy medicinal product under the Pharmaceutical Affairs Act and the regulation of cell therapy medical technique under the Medical Care Act. The new regulation framework regarding cell therapy medical technique announced by the Ministry of Health and Welfare (MOHW), has been in effect since 2018. The Center for Drug Evaluation (CDE) is commissioned by Department of Medical Affairs, MOHW to evaluate the technical part of those applications. By implementing the cell therapy medical technique, it is expected that cell therapy developers could accumulate experience in manufacturing and support the development of cell therapy medicinal product for commercialization.
This study analyzed the 65 applications with different cell processes from 2019 to 2021, involving 32 different Cell Processing Units (CPUs) in cell preparations and quality controls. The number of new CPUs was 20 in 2019, 7 in 2020, and 5 in 2021. The most common cell types in applications were cytokine-induced killer cells (CIK) and adipose tissue-derived stem cells (ADSC), with 17 each, followed by dendritic cells (DC)-CIK and bone marrow stromal cells (BMSC), with 8 and 7, respectively.
The total number of quality-relevant deficiencies in the 65 applications was 353, and the average number of deficiencies per application was decreased from 7 to 5 over the three years. The category with the most deficiencies was the analysis methods (31.7%), followed by manufacturing processes (19.8%), stability tests (11.9%), specifications (10.8%), reagents/materials control (10.5%), cell source control (7.9%), cell product (5.7%) and others (1.7%). The deficiencies were ranked in order, which were mycoplasma testing, sterile testing, representative batches, endotoxin testing, details of manufacturing processes, and transport stability, respectively.
Conclusion
The cell therapy industry in Taiwan has been active and has gained experience in cell manufacturing and controls by implementing cell therapy medical technique.
The quality-relevant deficiencies have decreased since CPUs accumulated experience in submitting applications. The most common deficiency category is analytical methods, mainly safety-relevant analytical methods. The fundamental problem with these deficiencies is that CPUs fail to provide representative data to support the cell preparations or analytical methods.
To promote the development of cell therapy medical technique and industry, the CDE has established a consultation mechanism and offers practical courses on safety-relevant analytical methods to guide CPUs in verifying the suitability of methods. For the next step, it is suggested to set up educational training courses to teach CPUs how to provide the representative data to support the application of cell therapy medical techniques.
