Registration of cell gene therapy product in Singapore
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
- is the result of only minimal manipulation of human cell or tissue;
- is intended for homologous use;
- is not combined or used with a therapeutic product and medical device
- 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.
- 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:
There are three application types and two evaluation pathway illustrated below:
- NDA-1 : For the first strength of a product containing a new CTGTP.
- 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.
- NDA-3 : For subsequent strengths of a product that has been registered or has been submitted as a NDA-1 or NDA-2.
- 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.
- 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
- Health Products (Cell, Tissue and Gene Therapy Products) Regulations 2021
- Chemistry, Manufacturing and Controls requirements for Cell, Tissue or Gene Therapy Product for Clinical Trials and Product Registration
- Guidance on Cell Tissue and Gene Therapy Products Registration in Singapore
- 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.