Draft Human Tissue Framework

Transcription

1 Draft Human Tissue Framework Pre-regulation Consultation 2 Mar 2018 Assoc/Prof Tan Soo Yong Senior Consultant Regulatory Policy and Legislation Ministry of Health

2 Human Biomedical Research Act (HBRA) Passed by Parliament in August 2015 being brought into operation gradually in phases Implementation Plan & Schedule Phase 1 : Administrative provisions Activated on 1 Jul 2016 Phase 2 : Prohibition against commercial tissue trading Activated on 1 Jan 2017 Phase 3 : Regulation of human biomedical research Activated on 1 Nov 2017 HBR Framework HTR Framework HBRA implementation plan and timelines Functions and duties of RI Functions and duties of IRB Approval and conduct of restricted research Amendment to Third, Fourth and Fifth Schedules of the HBRA In response to stakeholder concern and feedback on consent requirements & rhbr scope Phase 4 : Regulation of research tissue banking Target end of 2018 Duties of tissue bank (S34-36) and other controls to be prescribed Restrictions on activities relating to human tissue (S37) Compelling person to donate tissue (S38) Restriction on disclosure of information on tissue donor (S39) Savings & transitional provisions for legacy human biological material (64) 2

3 Definition of Human Tissue under the HBRA What is and what is not considered human tissue under the HBRA? Does the biological material contain human cells? Yes Is the human biological material ordinarily excreted or shed from the body? (e.g. hair, nail clippings, saliva, sweat, urine, faeces) No Has the human biological material been substantially manipulated*? (e.g. culture-expanded cells) No No Yes Yes Is the human biological material individuallyidentifiable? Yes No NOT Human Tissue Human Tissue *N.B. Processes that would not be considered to be substantial manipulation include cutting, grinding, shaping, centrifugation, soaking in antibiotic or antimicrobial solutions, sterilization, low-level irradiation, cell separation, concentration or purification, filtering, lyophilisation, freezing, cryopreservation, vitrification. 3

4 Definition of Tissue Bank under the HBRA Tissue bank means an individual or a body of persons, whether corporate or unincorporate, or other organisation, that carries on or conducts any tissue banking activity excludes an individual, a body of persons or an organisation that conducts any tissue banking activity solely for the purposes of the person s or organisation s own human biomedical research approved or exempted from review by an IRB. Tissue banking activity means 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. 4

5 Category of Tissue Bank Who is a Tissue Bank? Risk category General Tissue Bank High Risk Tissue Bank Risk profiles and tissue banking control Potential risk to patient safety and welfare General tissue banking requirements Risk to patient safety and welfare General tissue banking and additional requirements General tissue banking requirements administrative requirements such as notification, declaration of compliance and reporting of SAEs & other general tissue handling requirements Additional requirements Including good Tissue Practice (GTP) requirements and therapeutic banking standards that relate to preventing the introduction, transmission, or spread of communicable diseases by the human tissue for transplantational research. 5

6 Functions and duties of a Tissue Bank under the HBRA 1. Notify MOH before the commencement of any tissue banking activity Annual declaration of compliance Report Serious Adverse Events Exercise supervision & control over its tissue banking activities, including formulating policies & standards Appoint PIC to ensure compliance with regulatory requirements 4. System of tracking consent Release of tissue for research (local) Individually identifiable tissue Tissue Bank must sight IRB approval De-identified tissue Tissue Bank must sight IRB approval OR scientific review (e.g. public grant) Import or Export for research (overseas) Export of tissue for research: Consent must be obtained Letter of undertaking by receiving party (to be prescribed) Import of tissue for research: Consent given in accordance with the legal/ethical req. of that place 6

7 General Tissue Bank (TB): General tissue banking requirements # Types of Research TB Types of Banking Activities Controls 1 Large tissue repositories (e.g. Tissue Repository, Biobank/Tissue Network) 2 Smaller tissue banks (e.g. bio-techs, clinics) 3 Individual researcher who conducts tissue banking activity* May include the following : Removal Collection Store Supply Import Export General Requirements: a. Notification to MOH as TB b. Designate person in charge c. Annual declaration of compliance d. Reporting of SAE and contravention e. Coding & record system to track consent obtained f. Tissue release criteria and transfer agreement g. Requirements for tissue collection, storage, disposal *Note : Person(s) who conduct tissue banking activity solely for the purpose of the person(s) own IRB approved human biomedical research is excluded from definition of tissue bank 7

8 General Tissue Bank (TB): General tissue banking requirements # Types of Research TB Types of Banking Activities Controls 4 Tissue vendors or tissue service providers that collect human tissue and process them into tissue derivatives (non-tissue) (e.g. ipscs or DNA) before supplying them for use in future research. 5 Path labs with Formalin Fixed, Paraffin Embedded (FFPE) tissue blocks** N.B. Formalin fixation is considered substantial manipulation May include the following : Removal Collection Store Supply Import Export Biological material no longer human tissue at the point of supply, import or export. General Requirements: a. Notification to MOH as TB b. Designate person in charge c. Annual declaration of compliance d. Reporting of SAE and contravention e. Coding & record system to track consent obtained f. Tissue release criteria and transfer agreement g. Requirements for tissue collection, storage, disposal **Note : De-identified FFPE is not considered human tissue under the HBRA 8

9 De-identified FFPEs may be used without appropriate consent Operational workflow by path lab: Operating Theatre Pathology Lab Researcher Tissue De-identified FFPE Tissue is removed purely for treatment, research consent need not be obtained Consent not obtained Pathologists cannot take consent (not part of care team) But consent is required for supply/use of identifiable FFPE Consent not obtained Researcher does not need to obtain consent as deidentified FFPEs are not considered human tissue No consent needed As FFPEs are substantially manipulated, de-identified FFPEs are not considered human tissue under HBRA, and are therefore not subject to the consent requirements under the HTR. I.e. De-identified FFPEs may be used without appropriate consent However, MOH s current position is that path labs would still be considered tissue bank if they supply human tissue or human biological material for use in research facilitate current/ future research 9

10 Operational concerns and solutions Operational concern 3 : Formalin-fixed paraffin embedded (FFPE) tissue blocks stored in the pathology laboratory usually do not have appropriate consent for use in research, as they are collected and stored primarily for diagnostic purposes. De-identification mechanism for Path labs (Case study) Academic Informatics Office or Medical Record Office Re-identification key Tissue removal (therapy) Pathology data Link biopsy number to code Tissue Patient's data Path lab - Where the key to reidentification resides De-identified data (coded) De-identified FFPEs No appropriate consent needed Researcher - Request from AIO or MRO for FFPEs of certain characteristics/conditions 10

11 High Risk Tissue Bank (TB): Additional tissue banking requirements # Types of Research TB Types of Banking Activities Controls 1 Tissue banks with fresh frozen tissues for human applications/ transplants (e.g. cord tissue, cord blood, bone marrow) May include the following : Removal Collection Store Supply Import Export General Requirements: a. Notification to MOH as TB b. Designate person in charge c. Annual declaration of compliance d. Reporting of SAE and contravention e. Coding & record system to track consent obtained f. Tissue release criteria and transfer agreement g. Requirements for tissue collection, storage, disposal Additional Requirements: Including good tissue practice (GTP) & therapeutic banking standards that prevent the introduction & spread of communicable diseases 11

12 Appropriate consent requirement for dealings in human tissue in research General Rules : -For removal, storage, supply and use of tissues- 1. There must be appropriate consent. 2. The activity must be conducted in accordance with any conditions specified as part of the consent. Setting Diagnosis & Therapy Specific Controlling Provisions for Removal of Tissue 1. Where tissue is removed for a therapeutic or diagnostic purpose but will also be used for research purposes, appropriate consent must be obtained for the research purposes in addition to the consent obtained for the therapeutic or diagnostic procedure. 2. Cannot store, supply or use the tissue for research or any other purpose unless the medical practitioner or the healthcare institution has completed all the necessary therapeutic or diagnostic procedures. Research Where the tissue is to be removed for a research purpose, appropriate consent must be obtained for the tissue to be removed from the donor. Where the donor is an adult, consent is obtained from the donor. Where the donor is a minor with sufficient understanding and intelligence, consent is obtained from both the minor and at least one adult parent or guardian. 12

13 Appropriate consent for minor & adult donors who lack mental capacity Group Consent Additional Restriction Minors who (i) lack sufficient understanding and intelligence, or (ii) lack mental capacity Consent is obtained from at least one adult parent or guardian. The tissue is removed primarily for a therapeutic or diagnostic purpose. Not allowed to be used in restricted research Adults who lack mental capacity Donee/deputy Spouse adult son/daughter either parent/ guardian adult bro/sis named person The tissue is removed primarily for a therapeutic or diagnostic purpose. Not allowed to be used in restricted research IRB may waive the additional restriction if the board is satisfied that : a) the removal of tissue involves no more than minimal risk to the donor; AND b) there are reasonable grounds for believing that the proposed area of research cannot be carried out without the use of the tissue from such class of persons. 13

14 Taking of appropriate consent in healthcare institution Operational clarification : Appropriate consent may be obtained at any time during the patient s journey with the healthcare institution. One possible approach Centralised consent taking process Flow of patient Through care team Listing room Consent for therapy *Institution certifies that all the therapeutic/diagnostic procedures are completed Research Therapy or diagnosis Surgery Consent for research Advantage : Efficient use of PHI s resources and patient s waiting time 14

15 Appropriate consent requirement for dealings in human tissue in research NEW! Broad consent: If the specific purpose for which the tissue is intended to be used is not available, the purpose may be stated as for general research. MOH is exploring to allow human tissue collected before the appointed date to be used and stored without appropriate consent so long as they have limited consent and they will be de-identified before they are supplied for use in ethically approved research. 15

16 Legacy biological material can be used without appropriate consent Human Tissue Framework regulates research tissue bank and tissue banking activities ~ Targeting Q General Rules for removal, storage, supplying and use of human tissue for research : 1. There must be appropriate consent. 2. The activity must be conducted in accordance with any conditions specified as part of the consent. Legacy tissues Exception to facilitate the use of legacy tissues Legacy human biological material which had been removed from the donor s body AND rendered nonidentifiable, prior to the Act coming into force. Exception has been made to allow such nonidentifiable legacy tissues to be used in research without appropriate consent. Note: After the activation of the Human Tissue Framework, appropriate consent is required for the storage, supply and use of human tissue in research, regardless of whether the tissue is individually identifiable OR de-identified. 16

17 Summary of appropriate consent requirement for use of human tissue 1 Nov 2017 Appointed day E.g. 1 Nov 2018 HBRA not in force HBR framework activated Tissue framework activated Individually-identifiable biological material collected before 1 Nov 17 Individually-identifiable biological material collected after 1 Nov Obtain consent 2. IRB waiver (low bar) 1. Obtain consent 2. IRB waiver (higher bar) Biological material collected before e.g. 1 Nov 2018 and rendered de-identified consent not required for its use in research De-identified tissue also requires consent 15

18 Waiver of appropriate consent for tissue collected before and after 1 Nov 2017 Waiver of Requirement for Appropriate Consent for Historical ID HBM (before 1 Nov 2017) IRB must be satisfied that 1. The individually-identifiable human biological material was obtained or compiled before 1 November 2017; 2. the research cannot reasonably be carried out without the use of the human biological material in an individually-identifiable form; 3. the use of the individually-identifiable human biological material involves no more than minimal risk to the research subject; 4. the waiver concerned will not otherwise adversely affect the rights & welfare of the research subject; AND 5. reasonable effort has been made to re-contact the person to which the individually-identifiable human biological material relates for the purpose of obtaining his or her consent (e.g. Notification to be served by mail/electronically, subjects given days to respond*) Waiver of Requirement for Appropriate Consent for ID HBM (after 1 Nov 2017) IRB must be satisfied that 1. the research cannot reasonably be carried out without the use of the human biological material in an individually-identifiable form; 2. the process of obtaining consent from the person, to which the individually-identifiable human biological material relates, will involve a disproportionate amount of effort and resources relative to the research requirements. 3. the research involves no more than minimal risk to subject; 4. the waiver will not adversely affect the rights & welfare of the research subject or donor; 5. the research would reasonably be considered to contribute to the greater public good (e.g. epidemiology research & population wide study- BAC report 2002)- High Bar 16

19 Q & A

20 Basic requirements where all research TB have to comply To be prescribed in the Tissue Regulations S/N Requirement Details 1 Notification of tissue bank Supplementary Info on General Tissue Banking Requirements 2 Annual Declaration of Compliance 3 Designate a principal person in charge Similar to requirement for RI Submit to the Director in the applicable form set out at TIARAS Submit the notification no later than 30 days before the commencement of its first tissue banking activity / submit a notification to the Director no later than 30 days after the appointed day [existing TB] Similar to requirement for RI Period of Declaration of compliance to align with that for RI Submit to the Director, through such electronic means as the Director may require, on a date between 1st March and 18th April (both dates inclusive) of every year; and accompanied by the documents specified at TIARAS Similar to requirement for RI Is ordinarily resident in Singapore and is in the direct employment of, or acting for or by arrangement with, the tissue bank At all reasonable times be contactable by the Director Notify Director of any change to the information and particulars no later than 30 days after the date the tissue bank or the principal person in charge designated by the tissue bank first becomes aware of the change, whichever is the earlier 20

21 21 Supplementary Info on General Tissue Banking Requirements S/N Requirement Details 4 Reporting of suspected offence/contravention 5 Proper disposal of human tissue 6 Termination of the operation of a TB Similar to requirement for RI Reporting of suspected offence/contravention All relevant information is recorded; and Submitted to the Director as soon as possible and in any event not later than 7 days after the tissue bank or the principal person in charge designated by the institution first becomes aware of the information, whichever is the earlier. Proposed control Propose to include TB shall ensure that tissue is disposed off in a manner that would minimize the hazards to the Tissue Bank including personnel and the environment, in accordance with all existing local legislations and relevant guidelines. Proposed control Propose to include in the event that TB plans to cease the operation, the TB shall notify MOH in the form set out at TIARAS and be accompanied by a follow-up plan that includes The fate of the tissue - whether the tissue would be disposed off or transfer to another research TB Intention to notify the donor of the closure Any other information specified in TIARAS.

22 22 Supplementary Info on General Tissue Banking Requirements S/N Requirement Details 7 Maintaining an enduring consent tracking system 8 Release of human tissue for research 9 Exporting of human tissue Proposed controls Propose to include TB shall establish a system to be able to track the following information: When and where the human tissue is received The content and scope of consent obtained from the donor Any restriction, criteria or conditions on the use of tissue in accordance to the consent obtained from the donor Records of human tissue released and proper documentation for robust audit trail Withdrawal and change of consent by the donor Proposed controls Individual identifiable tissue : TB must sight the IRB approval and have a material transfer agreement with the receiving party to the use of the tissue in accordance to the consent preferences of donor. De-identified tissue : TB must sight IRB approval OR scientific review and have a MTA with the receiving party Proposed control TB shall ensure that the consent is obtained from the donor and maintain a proper documentation such as a Letter of Undertaking by the receiving party.

23 Supplementary Info on Additional Requirements for High Risk Tissue Bank Good Tissue Practice requirements aim to prevent the introduction, transmission, High Risk Tissue Bank or spread of communicable diseases which include but not limited to: 1. Quality Management Instruments and equipment shall be validated Tests and procedures shall be performed periodically 2. Facilities Maintained in a clean and sanitary condition Limited access to the TB 3. Mandatory screening test HIV, Hep B, Hep C and Syphilis Test by a clinical laboratory licensed under the Private Hospitals and Medical Clinics (PHMC) Act or overseas clinical laboratory accredited by a MOH-approved accreditation body 4. Practices All containers of tissue shall be clearly labelled 5. Information to be informed to the research upon tissue release 6. Recalling procedure 23