Therapeutic Goods (Standard for Human Cell and Tissue Products—Donor Screening Requirements) (TGO 108) Order 2021

I, John Skerritt, as delegate of the Minister for Health and Aged Care, make the following order.

Dated 24 September 2021

Adjunct Professor John Skerritt

Contents

Part 1—Preliminary

1  Name

2  Commencement

3  Authority

4  Definitions

5  Standard

6  Application

7  Transitional arrangements

8  Special transitional arrangements for cornea only manufacturers

Part 2—Requirements

9  General requirements

10  Medical and social history of donors

11  Blood samples—taking and testing

12  Physical assessment

Schedule 1—Ineligibility criteria for donor selection

Part 1—Preliminary

1  Name

 (1) This instrument is the Therapeutic Goods (Standard for Human Cell and Tissue Products—Donor Screening Requirements) (TGO 108) Order 2021.

 (2) This instrument may also be cited as TGO 108.

2  Commencement

 (1) Each provision of this instrument specified in column 1 of the table commences, or is taken to have commenced, in accordance with column 2 of the table. Any other statement in column 2 has effect according to its terms.

Note: This table relates only to the provisions of this instrument as originally made. It will not be amended to deal with any later amendments of this instrument.

 (2) Any information in column 3 of the table is not part of this instrument. Information may be inserted in this column, or information in it may be edited, in any published version of this instrument.

3  Authority

  This instrument is made under section 10 of the Therapeutic Goods Act 1989.

4  Definitions

Note: A number of expressions used in this instrument are defined in subsection 3(1) of the Act, including the following:

(a) export only medicine;

(b) manufacture;

(c) medicine;

(d) Register;

(e) standard;

(f) supply;

(g) therapeutic goods.

  In this instrument:

Act means the Therapeutic Goods Act 1989.

allogeneic use, in relation to an HCT product, means administration to, or application in the treatment of, a person other than the person from whom the HCT materials used in the manufacture of the product were collected.

asystole, in relation to a donor of HCT materials, means the reference time for cardiac death, being:

 (a) the documented pronounced time of death; or

 (b) if death is not witnessed—the last time the donor was known to be alive; or

 (c) if the donor of the HCT materials is also a solid organ donor—the cross-clamp time.

autologous use, in relation to an HCT product, means administration to, or application in the treatment of, the person from whom the HCT materials used in the manufacture of the product were collected.

blood means whole blood collected from a single human donor and that is:

 (a) used for infectious disease testing; or

 (b) processed either for transfusion or further manufacturing.

blood components means any of the following therapeutic components of blood that can be prepared by centrifugation, filtration or freezing using conventional methodologies in blood establishment:

 (a) plasma;

 (b) platelets;

 (c) red cells;

 (d) white cells;

but does not include haematopoietic progenitor cells.

directed allogeneic use, in relation to an HCT product, means allogeneic use for which all of the following paragraphs apply:

 (a) the HCT materials used in the manufacture of the product are collected by, or under the professional supervision or direction of, a medical or dental practitioner; and

 (b) the product is manufactured for administration to, or application in the treatment of, a designated patient who has a pre-existing condition by, or under the professional supervision or direction of, a medical or dental practitioner; and

 (c) the medical or dental practitioners mentioned in paragraphs (a) and (b) are registered in a State or internal Territory.

faecal microbiota transplant product has the same meaning as in the Regulations.

haematopoietic progenitor cells means primitive pluripotent haematopoietic cells capable of self-renewal as well as maturation into any of the haematopoietic lineages, including committed and lineage-restricted progenitor cells.

HBsAg means hepatitis B surface antigen.

HBV means hepatitis B virus.

HCT materials means one or more of the following that are collected from a donor for use in the manufacture of an HCT product:

 (a) human cells (including haematopoietic progenitor cells);

 (b) human tissues;

 (c) blood;

 (d) blood components (including plasma).

HCT products means therapeutic goods that comprise, contain or are derived from HCT materials.

HCV means hepatitis C virus.

HIV-1 means human immunodeficiency virus type 1.

HIV-2 means human immunodeficiency virus type 2.

HPC(CB) means haematopoietic progenitor cells obtained from cord blood.

HTLV-1 means human T-lymphotropic virus type 1.

HTLV-2 means human T-lymphotropic virus type 2.

human musculoskeletal tissue includes bone, cartilage, fascia lata, ligament, muscle, and tendon.

in-house IVD medical device has the same meaning as in the MD Regulations.

IVD medical device has the same meaning as in the MD Regulations.

MD Regulations means the Therapeutic Goods (Medical Devices) Regulations 2002.

NAT means nucleic acid amplification testing.

Regulations means the Therapeutic Goods Regulations 1990.

Therapeutic Goods Administration has the same meaning as in the Regulations.

5  Standard

  The matters specified in this instrument constitute a standard for HCT products in relation to donor screening.

6  Application

  This instrument applies to HCT products, other than:

 (a) a faecal microbiota transplant product; or

 (b) a sample of human cells or human tissues:

 (i) biopsied for in vitro diagnostic examination; and

 (ii) not for further manufacture, or reintroduction or transplant to a person; or

 (c) an HCT product for which all of the following subparagraphs apply:

 (i) the product is manufactured for autologous use only; and

 (ii) the HCT materials used in the manufacture of the product are collected by, or under the professional supervision or direction of, a medical or dental practitioner; and

 (iii) the product is manufactured for administration to, or application in the treatment of, a patient by, or under the professional supervision or direction of, a medical or dental practitioner; and

 (iv) the practitioners mentioned in subparagraphs (ii) and (iii) are registered in a State or internal Territory.

7  Transitional arrangements

 (1) In this section:

  former instrument means the Therapeutic Goods Order No. 88 Standards for donor selection, testing, and minimising infectious disease transmission via therapeutic goods that are human blood and blood components, human tissues and human cellular therapy products, as in force immediately before the commencement of the repeal instrument.

  repeal instrument means the Therapeutic Goods (Standards for Biologicals) Repeal Instrument 2021.

  transition period means the period beginning on 30 September 2021 and ending on 30 September 2022.

 (2) Despite the repeal of the former instrument by the repeal instrument, the former instrument continues to apply for the duration of the transition period, such that the standard for human cell and tissue products constituted by the former instrument may be conformed with as an alternative to the standard for human cell and tissue products constituted by this instrument.

8  Special transitional arrangements for cornea only manufacturers

 (1) In this section:

  cornea only manufacturer means a manufacturer who, in relation to a deceased donor:

 (a) collects human ocular tissue from the donor for the purpose of corneal transplantation and not any other purpose; and

 (b) does not collect any other tissue from the donor for any other purpose.

  repeal instrument means the Therapeutic Goods (Standards for Biologicals) Repeal Instrument 2021.

  special transitional requirements means the requirements specified in subsection (3) in relation to the testing of blood samples taken from a donor of human ocular tissue.

  special transition period means the period beginning on 30 September 2021 and ending on 30 September 2024.

 (2) The special transitional requirements apply to a cornea only manufacturer for the duration of the special transition period, such that those requirements may be complied with as an alternative to the blood sample testing requirements specified in paragraph 11(6)(b) and subsection 11(7) of this instrument.

 (3) Blood samples of a deceased donor of human ocular tissue collected in accordance with paragraph 11(6)(a) must be serology tested for HIV-1, HIV-2, HCV and HBsAg.

Part 2—Requirements

9  General requirements

 (1) An HCT product must be manufactured in accordance with procedures that mitigate the risk of infectious disease transmission.

 (2) An HCT product must not be released for supply, unless the applicable screening procedures and requirements specified in this instrument are satisfied.

 (3) Acceptance criteria based on microbial specifications must be applied to HCT materials used in the manufacture of an HCT product.

General requirements relating to testing of blood samples

 (4) Blood samples of a donor of HCT materials must be tested:

 (a) as soon as practicable after the blood sample is taken; or

 (b) in accordance with the timeframe specified by the manufacturer of the IVD medical device or the in-house IVD medical device that is used for testing the sample; or

 (c) where testing is conducted outside of Australia—within a timeframe that is validated by the testing laboratory.

 (5) Blood samples must be tested using IVD medical devices or in-house IVD medical devices that:

 (a) use the most appropriate methodology available that is validated for testing the samples (including cadaveric samples); and

 (b) where testing is conducted in Australia—are either included in the Register or exempt from the requirement to be included in the Register, or are the subject of an approval or authority under the Act; and

 (c) where testing is conducted outside of Australia—are:

 (i) approved by a relevant regulatory authority in the country in which the testing is conducted; and

 (ii) used in a facility that has been approved for such testing by a relevant regulatory authority in the country in which the testing is conducted; and

 (iii) considered acceptable by the Therapeutic Goods Administration.

 (6) Where the testing of a blood sample is conducted by a laboratory that is not under the direct control of the manufacturer of the relevant HCT product:

 (a) the testing must be conducted under a contract between the manufacturer and the laboratory; and

 (b) the contract mentioned in paragraph (a) must clearly set out the responsibilities of the manufacturer and the laboratory, and include arrangements to ensure that information relating to matters in this section and any other relevant details relating to the IVD medical devices or in‑house IVD medical devices used for such testing can be obtained from the laboratory.

 (7) The testing of blood samples must take into account all factors that may cause plasma dilution.

 (8) Where plasma dilution is suspected at a level sufficient to alter the test results in relation to a blood sample, and a pre-infusion sample is unavailable for testing, then:

 (a) an algorithm must be applied to assess the extent of plasma dilution; and

 (b) the extent of plasma dilution must be less than 50 per cent, unless use of samples with more than 50 per cent plasma dilution is validated by the manufacturer of the IVD medical devices or in-house IVD medical devices used for testing the sample.

 (9) Records must be maintained in relation to the following:

 (a) the tests performed in relation to blood samples and the results of those tests; and

 (b) the IVD medical device or in-house IVD medical device used for testing the samples; and

 (c) any test modifications; and

 (d) any evaluations of, or anomalies in, test results.

 (10) Procedures must be implemented for notifying a donor of HCT materials, a relevant health practitioner, a relevant hospital and any other relevant organisation, of a test result in relation to the donor that is indicative of a disease or carrier state.

10  Medical and social history of donors

Living donors

 (1) A medical and social history in relation to a living donor of HCT materials, covering the ineligibility criteria for donor selection specified in Schedule 1 and any other relevant matters, must be obtained by interview.

 (2) The interview must be:

 (a) conducted by an interviewer who is:

 (i) appropriately qualified and trained; and

 (ii) an employee of, or under a contract with, a person engaged in the collection of HCT materials or the manufacture of the HCT product; and

 (b) held face-to-face (to the extent that it is possible in the circumstances) with the donor or the donor’s guardian or next of kin; and

 (c) conducted within 30 days before or 30 days after the collection of the HCT materials, and

 (d) documented.

Deceased donors

 (3) A medical and social history in relation to a deceased donor of HCT materials, covering the ineligibility criteria for donor selection specified in Schedule 1 and any other relevant matters, must be obtained and documented within 7 days before or 7 days after the collection of the HCT materials, by:

 (a) both:

 (i) an interview with a person who is sufficiently informed about the donor’s medical and social history; and

 (ii) an examination of relevant documentation in relation to the donor; or

 (b) where the interview mentioned in subparagraph (3)(a)(i) is not possible—an examination of the donor documentation to ensure there is sufficient evidence to determine the acceptability of the donor’s medical and social history.

Example: A person who is sufficiently informed about a deceased donor’s medical and social history may include the donor’s treating physician, next of kin or closest available relative, a member of the donor’s household, or a person with a relationship with the donor, such as a carer, friend or partner.

Donors of HCT materials used exclusively for plasma fractionation

 (4) The periods of ineligibility specified in column 3 of items 2, 4, 13, 16 to 19, and 23 to 26 of the table in Schedule 1 do not apply in relation to a donor of HCT materials that are used exclusively for plasma fractionation in the manufacture of HCT products.

 (5) The periods of ineligibility specified in column 3 of items 1 to 7 and column 3 of items 9 to 26 of the table in Schedule 1 do not apply in relation to a donor of HCT materials that are used exclusively for plasma fractionation in the manufacture of an export only medicine.

Donors of HCT materials that are human ocular tissue only

 (6) The periods of ineligibility specified in column 3 of items 16 to 19 of the table in Schedule 1 do not apply in relation to a donor of HCT materials that are human ocular tissue only.

Change in circumstances of donor

 (7) Where the circumstances of a donor of HCT materials used in the manufacture of an HCT product change in relation to the ineligibility criteria for donor selection specified in Schedule 1, the relevant aspects of the medical and social history of the donor must be reviewed by the manufacturer of the HCT product with respect to those changes, before the HCT product is released for supply.

Screening requirements

 (8) An HCT product must not be released for supply, unless the medical and social history of a donor is reviewed and evaluated in accordance with this section.

 (9) Where a donor meets any of the medical and social history criteria specified in column 2 of an item of the table in Schedule 1, the donor must be subjected to the period of ineligibility specified in column 3 of that item, in relation to the collection of HCT materials from that donor for use in the manufacture of HCT products.

Screening in relation to donors less than 18 months old

 (10) If the donor is less than 18 months old, a medical and social history in relation to the donor’s birth mother, covering the ineligibility criteria for donor selection specified in column 2 of items 1 to 7, 11 to 13, 17 and 20 of the table in Schedule 1 must be obtained.

 (11) Where the donor’s birth mother meets the medical and social history criteria specified in column 2 of item 1 to 7, 11 to 13, 17 or 20 of the table in Schedule 1, then the donor must be subjected to the period of ineligibility specified in column 3 of that item, in relation to the collection of HCT materials from the donor.

Screening in relation to donors who have consumed breast milk

 (12) If the donor has consumed breast milk from a person (the relevant person) within the previous six months, a medical and social history in relation to the relevant person, covering the ineligibility criteria for donor selection specified in column 2 of the items 1 to 7, 11 to 13, 17 and 20 of the table in Schedule 1 must be obtained.

 (13) Where the relevant person meets the medical and social history criteria specified in column 2 of item 1 to 7, 11 to 13, 17 or 20 of the table in Schedule 1, then the donor must be subjected to the period of ineligibility specified in column 3 of that item, in relation to the collection of HCT materials from the donor.

HCT products that are manufactured for directed allogeneic use

 (14) Subsections (9), (11) and (13) do not apply in relation to HCT products that are manufactured for directed allogeneic use where the medical or dental practitioner who is responsible for the administration to, or application in the treatment of, the designated patient is provided the complete medical and social history of the donor of the HCT materials, including (where applicable) the medical and social history of the donor’s birth mother or the relevant person.

11  Blood samples—taking and testing

 (1) Blood samples must be:

 (a) taken from a donor of HCT materials; and

 (b) tested for the purpose of donor screening.

 (2) Blood samples must be taken using aseptic procedures.

Blood samples—living donors of HCT materials other than materials used exclusively for plasma fractionation

 (3) Subject to subsections (4) and (5) blood samples of a living donor of HCT materials must:

 (a) be taken within 7 days before, or 7 days after, the collection of the HCT materials from the donor; and

 (b) undergo both NAT and serology testing in accordance subsection (7).

 (4) Where an HCT product is able to be stored for more than 180 days without compromising the quality, safety or efficacy of the product, blood samples of a living donor of the HCT materials used in the manufacture of the product may instead:

 (a) be taken:

 (i) within 7 days before, or 7 days after, the collection of the HCT materials from the donor; and

 (ii) at least 180 days after the collection of the HCT materials from the donor; and

 (b) undergo serology testing in accordance with subsections (8) and (10).

Blood samples—living donors of HCT materials used exclusively for plasma fractionation

 (5) Blood samples of a living donor of HCT materials that are used exclusively for plasma fractionation must:

 (a) be taken within 7 days before, or 7 days after, the collection of the HCT materials from the donor; and

 (b) undergo both NAT and serology testing in accordance subsection (11).

Blood samples—deceased donors of HCT materials

 (6) Blood samples of a deceased donor of HCT materials must:

 (a) be taken:

 (i) in accordance with subsection 9(4); or

 (ii) within 7 days before the collection of the HCT materials; and

 (b) undergo NAT and serology testing in accordance with subsection (7).

Testing—living and deceased donors of HCT materials

 (7) Subject to subsection (9), the following testing must be conducted in relation to blood samples taken in accordance with paragraphs (3)(a) or (6)(a):

 (a) serology testing for HIV-1, HIV-2, HCV, HBsAg, HTLV-1, HTLV-2, and syphilis (Treponema pallidum); and

 (b) NAT for HIV-1, HIV-2, HBV, and HCV.

 (8) Subject to subsection (9), the following testing must be conducted in relation to blood samples taken in accordance with subparagraph (4)(a)(i):

 (a) serology testing for HIV-1, HIV-2, HCV, HBsAg, HTLV-1, HTLV-2, and syphilis (Treponema pallidum).

 (9) Serology testing for HTLV-1 and HTLV-2 is not required if a risk assessment, in relation to the type of the HCT materials and the geographical history of the donor, is undertaken, which demonstrates that:

 (a) the risk of transmission of HTLV-1 and HTLV-2 from the donor is mitigated in the absence of donor testing; and

 (b) the donor, the parents of the donor, and the sexual partners of the donor, originate from a low risk area; and

 (c) the HCT materials is not a viable leukocyte-rich cell or tissue.

 (10) The following testing must be conducted in relation to blood samples taken in accordance with subparagraph (4)(a)(ii):

 (a) serology testing for HIV-1, HIV-2, HCV, and HBsAg.

Testing—living donors of HCT materials used exclusively for plasma fractionation

 (11) The following testing must be conducted in relation to blood samples taken in accordance with paragraph (5)(a):

 (a) serology testing for HIV-1, HIV-2, HCV, and HBsAg; and

 (b) NAT for HIV-1, HIV-2, HBV and HCV.

Testing in relation to donors less than 18 months old

 (12) If a donor of HCT materials is less than 18 months old, then the donor’s birth mother must be subjected to the same testing requirements that are applicable to the donor, as set out in subsections (1) to (11).

 (13) In the case of a donor of the HCT materials that are HPC(CB) only, the applicable testing requirements in this section apply only in relation to the donor’s birth mother.

Note: An infant donor of HPC(CB) only is not required to be tested in accordance with this section.

Testing in relation to donors who have consumed breast milk

 (14) If a donor has consumed breast milk from a person (the relevant person) within the previous six months, then the relevant person must be subjected to the same testing requirements that are applicable to the donor, as set out in subsection (1) to (11).

Assessment of testing results

 (15) An HCT product must be placed in quarantine, and must not be released for supply, until the results of the testing mentioned in subsections (1) to (14) are assessed.

 (16) If the testing of a blood sample demonstrates a reactive result, then the relevant HCT product must not be released for supply.

 (17) Subsection (16) does not apply to an HCT product that is manufactured for directed allogeneic use where the medical or dental practitioner who is responsible for the administration to, or application in the treatment of, the designated patient is notified about the testing results.

Serum or plasma of blood samples

 (18) The serum or plasma of a blood sample taken from a donor of HCT materials in accordance with subsection (3), (4) or (6) must be:

 (a) archived at or below minus 25°C, or in accordance with conditions that are validated or recommended by the manufacturer of the IVD medical device or in‑house IVD medical device used for testing the samples; and

 (b) retained for a minimum of two years after the expiry date of the relevant HCT product, or for a period that is validated on the basis of validated data or documented evidence from relevant scientific literature.

 (19) If:

 (a) an HCT product has not been released for supply; and

 (b) following the testing of a blood sample in relation to the product, a protocol or methodology for the testing changes;

then, the archived serum or plasma of the blood sample must be tested in accordance with the new protocol or methodology before the product is released for supply, unless the testing is not required on the basis of a risk assessment.

12  Physical assessment

 (1) A physical assessment must be conducted in relation to a donor of HCT materials (other than a donor of HCT materials used exclusively for plasma fractionation in the manufacture of an export only medicine) as follows:

 (a) in the case of a living donor (other than a living donor of human musculoskeletal tissue only)—at the time of the collection of the HCT materials; or

 (b) in the case of a living donor of human musculoskeletal tissue only—within 30 days before or 30 days after the collection of the tissue; or

 (c) in the case of a deceased donor—before the collection of the HCT materials.

 (2) A physical assessment must:

 (a) include a clinical inspection of any physical features or characteristics of a donor (such as an abrasion, laceration, bruise, haematoma, fracture, tattoo, piercing, scar, skin lesion, or surgical incision) that may indicate that the donor poses a risk of infectious disease transmission; and

 (b) be conducted by a person who is:

 (i) appropriately qualified and trained; and

 (ii) an employee of, or under a contract with, a person engaged in the collection of HCT materials or the manufacture of HCT products; and

 (c) demonstrate that the donor does not pose a risk of infectious disease transmission.

Schedule 1—Ineligibility criteria for donor selection

Note 1: See section 10.

Note 2: The testing mentioned in column 3 of each item of this table (if any) must comply with the general requirements specified in subsections 9(4) to (10).