The Human Biomedical Research Act 2015 (HBRA) [1] sets out the regulatory frameworks for (i) human biomedical research, and (ii) human tissue in research. 

The objective of the Human Biomedical Research (HBR) Framework is to protect the safety and welfare of human research subjects and/or tissue donors, and to regulate the conduct of human biomedical research that are considered more sensitive. The objective of the Human Tissue Framework (HTF) is to protect the safety and welfare of tissue donors and to prohibit commercial trading of human tissue.

Human Biomedical Research (HBR) [2] covers two broad areas:

   1. Research that is intended to study:

          a. the prevention, prognostication, diagnosis or alleviation of any disease, disorder or injury affecting the human body; or

          b. the restoration, maintenance or promotion of the aesthetic appearance of human individuals through clinical procedures or techniques; or

          c. the performance or endurance of human individuals
AND where the research involves:

          d. subjecting an individual to any intervention (including any wilful act or omission) that has a physical, mental or physiological effect (whether temporary or permanent) on the body of the individual; or

          e. the use of any individually‑identifiable human biological material; or

          f. the use of any individually‑identifiable health information.

   2. Certain types of ‘sensitive’ embryological and stem cell research, as per section 3(3) of the HBRA.

Most cohort studies would be considered HBR under paragraph (1) above. To determine if your study is a HBR, a guide (decision tool) on the human biomedical research framework can be found here [1].

Under the Human Tissue Framework (HTF) [1], cohort custodians who conduct tissue banking activities are mandated to register the cohort as a tissue bank or associate themselves with existing tissue banks with the Ministry of Health (MOH), Singapore.

Under the HBRA, a tissue bank is defined as an individual or a body of persons, whether corporate or unincorporate, or other organisation that carries on or conducts any tissue banking activity but excludes an individual, a body of persons or an organisation that conducts any tissue banking activity solely for the purpose of the person’s or organisation’s own human biomedical research approved or exempted from review by an institutional review board.

Tissue banking activities refer to a structured and an organised activity involving human tissue for the purposes of facilitating current or future research or for public health or epidemiological purposes or any combination of such purposes including any of the following activities:

a. The collection, storage, procurement or importation of human tissue.

b. The supply, provision or export of human tissue.

An entity is still considered a Tissue Bank when it conducts the following activities (examples):

• • Storing leftover tissue from current Human Biomedical Research (HBR) or Clinical Trial for future research;

• • Collecting additional tissue beyond what is approved by HBR;

• • Utilising tissue beyond the objectives and endpoints of the protocol approved by the institutional review board (IRB) and/or regulatory agencies (e.g., Health Sciences Authority (HSA));

• • Providing leftover tissue to other researchers unrelated to one’s own study; or

• • Conducting pre-clinical studies (e.g., research conducted using human tissue before actual clinical trial starts).

Human tissues are defined as human biological material obtained from the human body that consists of, or includes, human cells. They are categorised by their source, variety, and processing methods:

• • Human cells, including red blood cells, peripheral blood mononuclear cells, white blood cells, and whole blood, are classified as human tissues. However, substances such as plasma, serum, DNA, and RNA are not deemed human cells due to significant manipulation.

• • Items like hair shafts (trimmed without the dermal hair root or follicle), nail plates (trimmed without the underlying dermal tissue), along with saliva, sweat, urine, faeces, and human breast milk do not fall under the category of human tissues since they are normally expelled from the body.

Legacy human biological material (HBM) refers to those collected and rendered non-identifiable before the Human Tissue Framework came into force on 1 November 2019 [1]. Only the following sections of the HBRA would apply for Legacy HBM:

• • Conduct of prohibited HBR (section 30);

• • Conduct of restricted HBR (section 31);

• • Prohibition against commercial trading of human tissue (section 32); and

• • Prohibition against advertisements relating to commercial trading of human tissue (section 33).

Any tissue collected before the activation of the Human Tissue Framework (on 1 November 2019) may only be used in future research if the donor’s consent was obtained, unless the tissue has been rendered non-identifiable before the activation of the Human Tissue Framework (i.e. legacy human biological material). The elements of information under Section 12(2)(a), 12(2)(f) and 12(2)(i) of the Act must be provided to the Tissue Donor before consent is obtained [1].

12(2)(a): the specific research purpose for which the tissue is intended to be used, if this information is available but if not available, the purpose for which the tissue is intended to be used may be stated as for general research;

12(2)(f): the donor’s right to withdraw his or her consent in the circumstances specified in section 14 and the limitations of such withdrawal as specified in that section;

12(2)(i): the extent to which records identifying the donor will be kept confidential;

In addition, the use of the Tissue must fall within the scope of the consent provided. To determine if your sample is a human tissue, or if you are conducting tissue banking activities, a guide (Decision Tool) on The Human Tissue Framework can be found here [1].

Appropriate consent is mandated under HBRA. Under the HBRA, ‘appropriate consent’ must be obtained for the conduct of (1) HBR and (2) handling of human tissue for research [1]. Appropriate consent must be obtained:

          a. in writing (which may be in electronic or other form of documentary evidence);

          b. from the research subject or tissue donor personally or from their legal proxy;

          c. after all information referred to in section 12 of the HBRA has been provided [except subsections 12(1)(e), 12(1)(j) and 12(2)(k) which should be provided only where applicable to the proposed study or tissue donation] and explained to the research subject or tissue donor or the legal proxy; and

          d. in the presence of a witness.

Waiver of requirements for appropriate consent by IRB may be granted based on the conditions stipulated in the HBRA Fifth Schedule. Key considerations to include in informed consent:

          a. Recontact: Participants’ personal identifiers are retained for the purpose of this study and future follow-ups, which include providing research updates and returning results or incidental findings, and/or for inviting them to participate in future studies.

          b. Data linkage: Consent is obtained to follow participants’ health and wellbeing through data linkage to various health records, such as disease registries, medical records, and national datasets, to meet research objectives.

          c. Secondary use of data and/or human biological material: Collected data and samples may be used for purposes beyond the initial research scope, such as teaching, training, health policy development, and future research studies with the goal to enhance future healthcare, the creation of health-related databases, records, technologies, and analytical tools, while acknowledging that it is not possible to list all future uses of the data and human biological materials.

          d. Sharing of data: Data and human biological materials may be shared with third partners including hospitals, universities, research institutes, and commercial companies, both locally and internationally, to maximise research benefits for the population, while describing data privacy safeguards that will be used.

          e. Tracking of consent and integrity of records: Tissue banks must have a system in place to ensure (i) that every donor’s consent in relation to each Tissue, under the supervision and control of the tissue bank, is accurately tracked and (ii) the integrity of records of the consent and other information relating to the donor [Section 17 – Human Biomedical Research (Tissue Banking) Regulations 2019].

Collection, storage, use and disclosure of participants’ personal data would be subjected to the regulatory framework of the Personal Data Protection Act 2012 (PDPA) [3]. Hence, it is important that PIs document their research methodologies clearly in the informed consent forms and research proposals for institutional review board (IRB) to review for legal compliance. There are 11 obligations under the PDPA that organisations handling personal data must meet and the references are available here.

Effective data management and stewardship is important for researchers of cohort studies as data is collected and stored over a long period of time. Therefore, the following information provides useful strategies to keep data safe, accessible, and secure. 

          a. Standardising data formats: Define the type, format, volume of data, detailed documentation and metadata. This strategy ensures data remains accessible and shareable over the long term. 

          b. Storage, Backup, and Security: Develop clear protocols for storage, backup processes, data security and access control, which adhere to international standards such as ISO 27001.

          c. Data Sharing Strategies: Develop protocols for data access, conditions under which data will be shared, and schedule for data release. 

          d. Assign a Trusted Third Party (TTP) to ensure an effective barrier is in place to prevent unauthorised use of personal data. 

          e. FAIR Principles: Adhere to FAIR Guiding Principles—ensuring data is Findable, Accessible, Interoperable, and Reusable. Following these principles improve the management and sharing of data [4,5,6].

          f. Licensing: Clarify data ownership and licensing terms early to promote transparency and accessibility while respecting intellectual property rights.