Registration of cell gene therapy product in Singapore

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Cell, tissue, gene therapy product (CTGTP) are health products intended for use in humans for a therapeutic, preventive, palliative or diagnostic purpose. CTGTP can contain any of the following and achieves its primary intended action by pharmacological, immunological, physiological, metabolic or physical means.

CTGTP products are divided into 2 classes namely:

Class 1 CTGTP product is deemed as lower risk product that 

1. is the result of only minimal manipulation of human cell or tissue;
2. is intended for homologous use;
3. is not combined or used with a therapeutic product and medical device
4. is assigned by the Authority as a Class 1 CTGT product due to a lower health risk to a user of the product

Examples: Bone grafts for orthopedic indications ,Scleral patch graft for ocular surgery

Class 2 CTGTP is deemed as a higher risk product which includes human cells or tissue that has been subject to more than minimal manipulation; or is intended for a non-homologous use; or is combined with a therapeutic product or a medical device.

Examples: gene modified cells, cells grown on scaffold , culture expanded cells and vectors with therapeutic gene.

Class 1 product registration requirements

Class 1 CTGTP are exempted from product registration. However, prior to supply, there is a need to notify the authority through an online application form. The processing timeline is about 14 working days and it costs $90 per application.

Requirements include:

• Application form
• Table of contents
• Cover letter
• Certified true copy of a valid certificate of accreditation (e.g. American Association of Blood Banks [AABB], American Association of Tissue Banks [AATB], Foundation for the Accreditation of Cellular Therapy [FACT], the College of American Pathologists [CAP])
• Evidence demonstrating that the establishment is registered with local regulatory agency (e.g. US FDA establishment registration and listing for HCT/Ps [human cells, tissues, and cellular and tissue-based products], Health Canada Cells, Tissues or Organs registration certificate, UK Human Tissue Authority)
• Product release specifications or Certificate of Analysis
• Package insert
• Product label
• Product shelf-life and container closure (packaging) information
• List of Class 1 CTGTP checklist

Class 2 product registration requirements

Class 2 CTGTP needs to registered with the authority  before it can be supplied. The processing timeline will takes about 230-320 working days depending on the evaluation route. It costs about $30,000 per application inclusion of overseas GCP inspection. The requirements are briefly presented below:

Application type:

There are three application types and two evaluation pathway illustrated below:

1. NDA-1 : For the first strength of a product containing a new CTGTP.
2. NDA-2 : For the first strength of a product containing: New combination of registered CTGTP in either of the following:

• New dosage form, such as capsules and injectables.
• New presentation, such as single-dose vials, multi-dose vials and pre-filled syringes.
• New formulation, such as preservative-free.
• Registered CTGTP for use by a new route of administration.

3. NDA-3 : For subsequent strengths of a product that has been registered or has been submitted as a NDA-1 or NDA-2.

Evaluation route:

• Full route: Applies to any new product that has not been approved by any comparable overseas regulator at the time of application submission to HSA.
• Abridged route: Applies to any new product that has been approved by at least one of our comparable overseas regulators.

#Comparable overseas regulators: TGA, Health Canada, FDA, EMA and MHRA.

Documentary requirements:

• CMC requirements: Module 3.2.S to Module 3.2.P .Detailed requirements are as per Appendix 8.
• Non-clinical requirements: Comply with ICH CTD Guidelines M4S (Safety) technical guidelines
• Clinical requirement: Comply with ICH CTD Guideline M4E (Efficacy) technical guidelines, in particular the ICH E3 guidance document on Structure and Contents of Clinical Study Reports

References:

1. Health Products (Cell, Tissue and Gene Therapy Products) Regulations 2021
2. Chemistry, Manufacturing and Controls requirements for Cell, Tissue or Gene Therapy Product for Clinical Trials and Product Registration
3. Guidance on Cell Tissue and Gene Therapy Products Registration in Singapore
4. Guideline on Notification Process for Class 1 Cell, Tissue or Gene Therapy Product

We hope this article is useful to provide you a brief insight into how cell gene therapy products are regulated in Singapore. Feel free to share with your peers . If  you need help or support to evaluate the readiness of your dossier please feel free to contact us.

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