Introduction

Regenerative medicine is an innovative and rapidly evolving field that leverages genes, cells, and their derivatives to reconstruct or repair human body structures and functions, ultimately aiming to treat or prevent diseases. This field has the potential to revolutionize healthcare by offering new therapeutic options for conditions that are currently difficult or impossible to treat with conventional medicine.

In Taiwan, regenerative medicine is categorized into regenerative medical technology and regenerative medical preparations, each of which is regulated by distinct frameworks to ensure safety, efficacy, and compliance with international standards. The regulatory oversight is managed by the Taiwan Food and Drug Administration (TFDA), along with the Center for Drug Evaluation (CDE) and other relevant authorities. The regulations continue to evolve to keep pace with scientific advancements and ensure that Taiwan remains competitive in the global biomedical industry.

Regulatory Classification

Regenerative Medical Technology

Regenerative medical technology in Taiwan is governed by the Medical Act and the Regulations on the Implementation or Use of Specific Medical Technology Inspections and Medical Instruments. These regulations outline the scope of regenerative medicine and define the criteria for its approval and oversight.

The key definitions within this regulatory framework include the following:

1. Human Cell Tissues refer to human cells, tissues, body fluids, or derivatives that are obtained through non-genetic engineering methods.
2. Specific Medical Technology encompasses medical procedures such as cell therapy, cosmetic surgery, and other restricted medical technologies that require regulatory approval.
3. Cell Therapy Technology involves the use of human cell tissues, without the combination of drugs, to reconstruct body structures, restore function, or treat diseases. However, certain medical procedures are excluded from this classification, including blood transfusion, blood preparation, bone marrow and peripheral blood hematopoietic stem cell transplantation, artificial reproduction, and other exclusions as designated by the central competent authority.

 

Regenerative Medical Preparations

Regenerative medical preparations are classified as biological drugs and are regulated under the Pharmaceutical Affairs Act and the draft Regenerative Medical Preparations Regulations. These preparations contain genes, cells, and their derivatives and are specifically developed for human therapeutic purposes.

There are four main categories of regenerative medical preparations:

1. Gene Therapy Preparations refer to medications that introduce recombinant genes into the human body to treat, prevent, or diagnose diseases.
2. Cell Therapy Preparations consist of products made by processing cells or their derivatives, which are then used for therapeutic, preventive, or diagnostic purposes.
3. Tissue Engineering Preparations include processed and modified tissues or cells designed to repair, regenerate, or replace damaged human tissues and organs.
4. Composite Preparations are a combination of medical devices and regenerative medical products, formulated to enhance overall therapeutic outcomes.

Registration Process

Regenerative Medical Technology

Medical institutions intending to perform cell therapy must submit applications through the Cell Therapy Technology Case Submission Window of the Center for Drug Evaluation (CDE). The application process involves multiple steps, ensuring a thorough review before approval.

Step-by-Step Application Process

The registration process for regenerative medical technology begins with preliminary registration, where medical institutions must submit their proposed implementation plan to the CDE. Once registered, they receive a tracking number, which is used throughout the approval process.

Following registration, institutions must proceed with the application submission phase, during which they submit a full application along with the necessary supporting documents to both the TFDA and CDE. The submission package should include the physician’s qualification proof, evidence of an accredited cell preparation site, and a detailed implementation plan outlining the scope and methodology of the proposed therapy.

The approval process depends on whether human trials are required. For therapies that do not necessitate human clinical trials, the approval is relatively streamlined. However, for therapies that require additional scrutiny, institutions may need to provide clinical trial data and additional documentation before obtaining approval.

Fast-Track Therapies

Certain well-established cell therapies benefit from an expedited approval process, as they have been deemed low-risk based on previous successful applications and regulatory precedent. These therapies include:

• Autologous CD34+ selection peripheral blood stem cell therapy
• Autologous immune cell therapy (e.g., CIK, NK, DC, TIL, gamma-delta T)
• Autologous adipose stem cell therapy
• Autologous fibroblast therapy
• Autologous bone marrow mesenchymal stem cell therapy
• Autologous chondrocyte therapy

For cell therapies not included in the fast-track list, institutions must submit Phase II human clinical trial data, as well as supporting domestic and international literature that demonstrates the safety and efficacy of the proposed therapy.

Practitioner Requirements

To ensure patient safety and maintain high-quality standards, physicians who perform cell therapy techniques must meet the following requirements:

• They must be specialists in a relevant field with experience in regenerative medicine.
• They must complete TFDA-accredited training courses that provide an in-depth understanding of cell therapy techniques and safety protocols.
• They should have actively participated in clinical trials related to the specific cell therapy being implemented.

Additionally, cell preparation sites must adhere to Good Tissue Practice (GTP) standards and receive official accreditation before commencing operations. This accreditation ensures that the preparation and handling of cells meet stringent regulatory and quality control measures.

Once approved, medical institutions must comply with post-approval obligations, which include reporting treatment outcomes and monitoring for adverse reactions. If significant adverse events occur, the institution may be required to modify or halt the therapy in accordance with TFDA guidelines.

Regenerative Medical Preparations

Regenerative medical preparations follow biologics and biosimilars regulatory pathways, ensuring that all products meet stringent quality and safety requirements before reaching the market. The process involves site registration and product registration, which are essential steps for manufacturers seeking approval to distribute their regenerative products.

Site Registration

Manufacturers of regenerative medical preparations must undergo site registration, which includes inspections and reviews to verify compliance with Good Manufacturing Practice (GMP) standards. The requirements for site registration differ based on the country of origin of the manufacturer:

• Non-PIC/S Member Countries: Manufacturers located in countries that are not members of the Pharmaceutical Inspection Co-operation Scheme (PIC/S) must undergo foreign on-site GMP inspections by TFDA. These inspections evaluate the production facilities and ensure compliance with international safety and quality standards.
• PIC/S Member Countries: Manufacturers from countries that are part of PIC/S may submit a Plant Master File (PMF) review instead of undergoing an on-site inspection. The PMF review provides detailed documentation of the manufacturing process, site controls, and compliance with GMP requirements.

Product Registration

Once the manufacturing site has been approved, the next step is product registration, which requires manufacturers to submit an application in the Common Technical Document (CTD) format. The CTD is an internationally recognized standard for regulatory submissions and ensures consistency in the evaluation process.

To facilitate the submission process, TFDA mandates that all applications be submitted electronically through the ExPress eCTD platform. This digital platform allows for streamlined review and tracking of applications, reducing administrative burdens and improving efficiency.

The product registration process includes a comprehensive review of:

• Preclinical data demonstrating the safety and efficacy of the preparation.
• Clinical trial results, where applicable, to support product claims.
• Manufacturing quality control measures ensuring product consistency and compliance with regulatory standards.

Registration Timelines

1. Regenerative Medical Technology

The overall timeline for regenerative medical technology approval is approximately 6 to 9 months, including:

1. CDE Registration – 7 days
2. Administrative Screening – 14 days
3. Technical Review – 30 days
4. Final Approval – 30 days
5. GTP Certification – 60 days

2. Regenerative Medical Preparations

Approval for biologic and biosimilar products follows a longer timeline:

• PMF Review – 200 days (excluding deficiency response periods)
• Technical Document Review – 90 days
• Biologics Product Registration – 360 days
• Biosimilar Product Registration – 300 days

Compliance and Oversight

The Taiwan Food and Drug Administration (TFDA) maintains strict oversight of regenerative medical technology and preparations by conducting routine and unscheduled inspections of medical institutions and cell preparation sites. These inspections ensure compliance with Good Tissue Practice (GTP) and Good Manufacturing Practice (GMP) regulations and help maintain the safety and efficacy of regenerative medicine procedures and products.

The TFDA’s compliance framework is designed to prevent misconduct, ensure adherence to approved protocols, and mitigate risks associated with regenerative medical treatments. Medical institutions and manufacturers must follow strict operational and reporting requirements, and any violations may lead to regulatory actions, including suspension or revocation of approvals. Institutions may face penalties if they:

• Deviate from their approved treatment plan – Medical institutions must strictly follow the approved protocols for regenerative medicine. Any modifications to the plan require prior approval from the TFDA.
• Fail to report adverse events – If a patient experiences an adverse reaction or an unexpected outcome related to regenerative therapy, the institution must promptly report the event to the TFDA. Failure to do so can result in sanctions and suspension of the therapy.
• Do not submit mandatory annual reports – Institutions conducting regenerative medical procedures must provide annual reports detailing treatment outcomes, patient responses, and any adverse effects. These reports allow regulators to monitor safety and effectiveness over time.
• Violate GTP or GMP regulations – All cell preparation sites must adhere to GTP standards, ensuring the highest quality in cell handling, processing, and storage. Similarly, manufacturers of regenerative medical preparations must comply with GMP regulations to maintain product safety and consistency.

In addition to routine inspections, the TFDA has the authority to conduct surprise audits, review documentation, and impose corrective actions if non-compliance is detected. If an institution fails to address compliance issues within a specified timeframe, the TFDA may suspend or revoke the institution’s ability to provide regenerative medical treatments.

By maintaining a rigorous compliance and oversight framework, the TFDA helps safeguard public health and uphold the credibility of Taiwan’s regenerative medicine sector. These regulations ensure that only safe, effective, and high-quality regenerative therapies reach patients, fostering continued innovation while prioritizing patient safety.

Conclusion

Taiwan’s regulatory framework for regenerative medicine ensures strict oversight and adherence to global safety and efficacy standards. As the field continues to advance, Taiwan remains committed to fostering innovation while prioritizing patient safety and regulatory compliance.

 

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Written by: Ames Gross – President and Founder, Pacific Bridge Medical (PBM)

Mr. Gross founded PBM in 1988 and has helped hundreds of medical companies with regulatory and business development issues in Asia. He is recognized nationally and internationally as a leader in the Asian medical markets. Mr. Gross has a BA degree, Phi Beta Kappa, from the University of Pennsylvania and an MBA from Columbia University.