Public Consultation on the Proposed Regulation for Cell, Tissue and Gene Therapy Products under the Health Products Act

Introduction

1.       The Health Sciences Authority (HSA), a statutory board of the Ministry of Health (MOH), invites stakeholders to provide feedback on the following 2 new pieces of legislation:

(A) Proposed Health Products Act (Amendment of First Schedule) Order 2020; and   

(B) Proposed Health Products (Cell, Tissue and Gene Therapy Products)   Regulations 2020.

2.       The Health Products Act (HPA) provides the legislative and licensing framework for different categories of health products. Currently, medical devices, cosmetic products, therapeutic products and oral dental gums are regulated under the HPA. HSA is introducing a new category of health products, namely cell, tissue and gene therapy products (CTGTP), in the First Schedule to the HPA.

3.       CTGTP comprising stem cells, tissues and genetically modified organisms are a new class of health products. Cells and tissues can be engineered to grow healthy and functional tissues to reconstruct, regenerate or repair damaged tissues or organs; or new genes introduced into the body to treat or cure diseases. This area of therapy is developing rapidly and has the potential to transform the current practice of medicine and offer potential cures for chronic and debilitating diseases.

(A) Proposed Health Products Act (Amendment of First Schedule) Order 2020

4.       In order to bring the controls for CTGTP under the HPA, the First Schedule of the Act needs to be amended to specify and define this category of products in the Schedule.

5.       The proposed definition of CTGTP refers to a substance containing human cells or tissues that are either autologous (obtained from the same individual) or allogeneic (obtained from another individual), viable animal cells or tissues, or recombinant nucleic acids (i.e. modified DNA or RNA as carriers of a therapeutic gene); that is intended for diagnosis, treatment or prevention of any human disease or medical condition. Examples of CTGTP include human demineralised bone, cell therapy products, stem-cell derived products, tissue-engineered products, gene therapy products, xenogeneic products and regenerative medicine products. 

(B) Proposed Health Products (Cell, Tissue and Gene Therapy Products) Regulations 2020

6.       The objectives of the proposed CTGTP Regulations are:

(i) To facilitate patients’ access to medically important therapies that meet appropriate standards of safety, efficacy and quality; and

(ii) To provide a fit-for-purpose regulatory framework that supports product development and facilitates product commercialisation.

Overview of the proposed regulations

Risk-based product classification and controls

7.       CTGTP will be risk-stratified into two classes as follows:

(i) Class 1 CTGTP (lower risk) have to satisfy ALL the following criteria:

• minimally manipulated, i.e. biological characteristics or functions of the cells or the structural properties of the tissues are not altered;

• intended for homologous use, i.e. performing same function and administered at the same anatomical site or histological environment in the recipient as in the donor; and

• not combined or used in conjunction with therapeutic products or medical devices

(ii) Class 2 CTGTP (higher risk) are those that do not meet the criteria for Class 1 CTGTP.

Licensing controls for dealers

8.       The level of control for the activities of manufacture, import and supply is calibrated to the degree of manipulation of the product. CTGTP that are minimally manipulated have a lower risk and are subjected to minimal controls as they pose less risk and patient safety concerns. CTGTP that are more than minimally manipulated may carry significant risk regarding unintended tumour formation, immune rejection, genome integration and potential environmental contamination. Hence, rigorous assessment that is relevant to the manufacturing process for CTGTP that are more than minimally manipulated will be required.   

9.       A risk-based licensing approach based on the degree of manipulation of the CTGTP is proposed (see Table 1). Manufacturers, importers and wholesalers handling minimally manipulated CTGTP will not require dealers’ licences but will be required to notify HSA of their activities. They will be required to comply with the respective manufacturer’s, importer’s and wholesaler’s duties and obligations as specified in the CTGTP Regulations. These requirements include maintaining the appropriate quality standards (Table 1), record keeping, safety reporting, product defect reporting and ensuring traceability of the product.

10.      For manufacturers, importers and wholesalers handling CTGTP that are more than minimally manipulated, the respective dealers’ licences (manufacturer’s, importer’s and wholesaler’s licences) will apply. HSA will conduct pre-approval audit assessment of the dealer to the appropriate quality standard (Table 1) before issuing the respective licences. Pre-approval audit assessment will entail the assessment of the manufacturer’s quality management system to ensure that CTGTP are consistently manufactured in accordance to quality standards. The assessment of the distribution practices of the importer and wholesaler is to ensure that the quality and integrity of the products are maintained during handling, storage and distribution. The licensee has to comply with the duties and obligations specified in the CTGTP Regulations. For information on good distribution practice and CTGTP good manufacturing practice standards, please refer to the attached guidance documents.

Table 1: Dealer’s licences and applicable quality standards for dealers of CTGTP

GTP: Good Tissue Practice Standard

GDP: Good Distribution Practice Standard

GDP-MDS: Good Distribution Practice Standard for Medical Devices

CTGTP GMP: CTGTP Good Manufacturing Practice Standard

Product registration

11.      The risk classification of CTGTP described in paragraph 7 will be used to determine the registration requirements as summarised below: 

(i) Product registration for Class 1 CTGTP will not be required. However, the supplier will be required to notify HSA of the product and must receive HSA’s written acceptance before it can be supplied. The supplier will also be required to ensure that the product is sourced from an accredited/licensed facility and that it is free from infectious agents.

(ii) Product registration, in accordance to the appropriate standards for quality, safety and efficacy for the intended use, will be required prior to the supply of Class 2 CTGTP.

Clinical trials

12.      A risk-based approach will be taken for the regulation of clinical trials of CTGTP.

13.      Clinical trials of Class 2 CTGTP will be regulated under the existing Clinical Trial Authorisation (CTA)- Clinical Trial Notification (CTN) clinical trial framework.

14.      Clinical trials of Class 1 CTGTP will not be regulated by HSA. Such research will be regulated under the Human Biomedical Research Act and must be conducted under the supervision of a research institution (RI) that has notified MOH of its operation. The research must also be reviewed and approved by the RI’s appointed Institutional Review Board.

Other requirements

15.      All dealers and product registrants must comply with the duties and obligations prescribed in the regulations such as with respect to labelling, reporting of defects and serious adverse effects, and notification of product recalls.

16.      Requirements that are unique to CTGTP include having a traceability system to enable bi-directional tracking of CTGTP from the point of sourcing, through manufacturing, up to the administration of the product to the patient and vice versa. Dealers and product registrants should maintain the records of traceability for 30 years after the expiry of the product.

17.      Prior to the use of any unregistered Class 2 CTGTP, healthcare practitioners shall inform and obtain consent from the patient/legal guardian that the product is not registered with HSA and not evaluated for its quality, safety and efficacy.[1]

18.     HSA welcomes feedback on the proposed CTGTP Regulations. This consultation will be from 6 November 2020 to 27 November 2020.

19.      Please provide your name, the organisation you represent, contact number and email address if you would like us to follow up with you to clarify your enquiries. Where possible, you should highlight the provisions in the proposed draft Regulations for which you are providing feedback.

20.      Please note that the contents of any written feedback submitted, and the identity of the source, may be disclosed at the conclusion of this consultation. You may request for the feedback provided to be treated with confidence if the information is proprietary, confidential or commercially sensitive. Such requests will be taken into consideration.

21.      Please provide your feedback by 27 November 2020 (Friday). Scan the QR code below or click HERE to access the feedback form.

HEALTH SCIENCES AUTHORITY
6 NOVEMBER 2020

Proposed Health Products Act (Amendment of First Schedule) Order 2020 [PDF, 85 KB]

Proposed Health Products (Cell, Tissue and Gene Therapy Products) Regulations 2020  [PDF, 283 KB]

Guidance Notes on Good Distribution Practice - Draft  [PDF, 730 KB]

Guidelines on Good Manufacturing Practice for Cell, Tissue and Gene Therapy Products - Draft [PDF, 1647 KB]

[1] Under the Healthcare Services Act under the Ministry of Health, the administration of any CTGTPs for a clinical (non-research) purpose will be a licensable healthcare service that is expected to take effect in Q1 2023.  In the meantime, all healthcare institutions and healthcare professionals in Singapore should abide by MOH’s current requirements for CTGTPs, such as any MOH directives under the Private Hospitals and Medical Clinics Act.