Perspectives on Challenges to Cell Therapy Development in Taiwan: Strengthening Evidential Standards and Ways Forward

Abstract

Over the past years, the field of regenerative medicine and cell therapy has garnered much interest, extending beyond the bench to broader use, and commercialization. These therapies undergo stringent regulatory oversight as a result of their complexities and potential risk across different jurisdictions. Taiwan's government, with the aim of developing the country as a hub for regenerative medicine in Asia, enacted a dual track act to promote the development of regenerative and cell therapy products. This qualitative study used purposive sampling to recruit sixteen experts (Twelve respondents from medical institutions and four respondents from the industry) to understand their perspectives on one of the regulatory tracks which governs the medical use of cell technologies and challenges regarding its implementation. Semi-structured interviews were conducted, transcribed, coded and thematically analyzed. Three major themes emerged from the analysis: 1) Perceptions of the "Special Regulation for Cell Therapy" 2) Emerging issues and controversies on the medical use of cell technologies in private clinics, and 3) Challenges impeding the clinical innovation of cell technologies. As reported by the experts, it was clear that the special regulation for cell therapy was aimed at legalizing the clinical use of cell therapy in a similar fashion to an evidence-based pathway, to promote clinical innovation, ensure manufacturing consistency, and improve oversight on cell-based therapies. Thus, the regulation addresses the issues of safety concerns, patient's access and stem cell tourism. However, the limited approved cell techniques, quality control during cell processing, time, and criteria used in evaluating applications in addition to the need to develop evidential standards for clinical evidence are some of the difficulties faced. Thus, policy interventions on funding, educational resources, training, and regulatory clarity addressing these challenges may positively impact clinical innovation of cell therapy in Taiwan.

Keywords: Taiwan; cell-based therapy; clinical evidence; qualitative research; regenerative medicine; regulation.

FIGURE 1

Taiwan’s dual track regulatory framework. The special regulation permits the use of six types of autologous cell techniques in medical institutions by approved physicians under the Good Tissue Practices (GTP), while the regenerative medicinal act permits the manufacturing of medicinal products by pharmaceutical industry under the Good Manufacturing Practices (GMP).

FIGURE 2

A step-wise process of approval for medical practice and products. For medical practice, the safety of a listed cell technology is reviewed by the cell therapy committee for approval. Once its efficacy is confirmed, such cell technology can be turned into a routine practice. Otherwise, it will be annulled. For unlisted cell technology, it needs to undergo clinical testing before being approved by the committee for cell therapy as a medical practice. Regenerative products or biologics need to undergo a stepwise clinical testing from phase I-III before being granted a market authorization. However, a conditional approval of 5 years is allowed after preliminary safety and efficacy results are provided.

FIGURE 3

(A) The standard IND review takes 150 days while an expedited review takes 30 days. On the other hand, the NDA application, it takes 360, 180, and 240 days for standard, abbreviated and priority reviews respectively.conditions for expedited review (B) Sponsors, hospitals and CROs file application through the TFDA. Application is sent to the CDE review section which reviews the technical dossiers for conclusion. Report may be sent to the advisory committee if need be. The overall report from both the CDE and advisory committee will be submitted to the TFDA for final decision making.

FIGURE 4

(A) The percentage of hospitals approved for each of the cell technologies (B) The number of applications approved for each of the indications. Abbreviations: NK, Natural Killer cell; NKT, Natural Killer-T cells; CIK, cytokine induced killer T cell; DC, dendritic cell; BM-MSC, bone marrow mesenchymal stem cells.