Part 1—Preliminary
1 Name
This instrument is the Therapeutic Goods (Manufacturing Principles) Determination 2020.
3 Authority
This instrument is made under section 36 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) biological;
(b) licence;
(c) manufacture;
(d) manufacturing principles;
(e) medicine;
(f) standard; and
(g) therapeutic goods.
In this instrument:
Act means the Therapeutic Goods Act 1989.
active pharmaceutical ingredient means any substance or mixture of substances intended to be used in the manufacture of a medicine and that, when used in the manufacture of a medicine, becomes an active ingredient of that medicine.
Note: An active pharmaceutical ingredient is intended to furnish pharmacological activity or other direct effect in the diagnosis, cure, mitigation, treatment, or prevention of disease or to affect the structure and function of the body.
Australian Code of Good Manufacturing Practice means the Australian Code of Good Manufacturing Practice for human blood and blood components, human tissues and human cellular therapy products (Version 1.0, April 2013) published by the Therapeutic Goods Administration, as in force or existing at the commencement of this instrument.
Note: The Australian Code of Good Manufacturing Practice is published on the TGA website at www.tga.gov.au.
blood means whole blood collected from a single human donor and 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) red cells;
(b) white cells;
(c) platelets;
(d) plasma;
but does not include haematopoietic progenitor cells.
haematopoietic progenitor cells means self-renewing or multi-potent stem cells, or both, capable of maturation into haematopoietic lineages, lineage-restricted pluri-potent progenitor cells, or committed progenitor cells.
PIC/S means the Pharmaceutical Inspection Co-operation Scheme established in 1995 as an extension to the Pharmaceutical Inspection Convention.
PIC/S Guide to GMP means the document titled Guide to Good Manufacturing Practice for Medicinal Products (PE 009-16, 1 February 2022) published by PIC/S, as in force or existing at 3 June 2024, and includes the Annexes to that document other than the following:
(a) Annex 4 (Manufacture of veterinary medicinal products other than immunologicals);
(b) Annex 5 (Manufacture of immunological veterinary medical products);
(c) Annex 14 (Manufacture of medicinal products derived from human blood or plasma).
plasma means plasma, separated from human donor blood, intended for a number of purposes including the manufacture of further blood components, the manufacture of which is required to be licensed under Part 3-3 of the Act.
PMF Guideline means the Guideline on the Scientific Data Requirements for a Plasma Master File (PMF) Revision 1 (2006) (EMEA/CHMP/BWP/3794/03 Rev. 1) published by the European Medicines Agency, as in force or existing at the commencement of this instrument.
Note: The PMF Guideline is published on the European Medicines Agency website at www.ema.europa.eu.
relevant officer means an officer of the Therapeutic Goods Administration.
technical master file, in relation to the manufacture of therapeutic goods that are blood, blood components or haematopoietic progenitor cells, means:
(a) compilations of scientific and technical data provided by a manufacturer, including a description of the steps of manufacture that is consistent with the TMF Guideline; and
(b) detailed scientific and technical data or information that must satisfy a relevant officer that:
(i) in relation to the manufacture of blood or blood components—the therapeutic goods conform to TGO 102;
(ii) in relation to the manufacture of haematopoietic progenitor cells derived from cord blood—the therapeutic goods conform to TGO 94;
(iii) in relation to the manufacture of blood, blood components, or haematopoietic progenitor cells—the therapeutic goods conform to TGO 108.
TGO 94 means the Therapeutic Goods Order No. 94 (Standard for Haematopoietic Progenitor Cells derived from Cord Blood) 2017.
Note: TGO 94 is published on the Federal Register of Legislation at www.legislation.gov.au.
TGO 102 means the Therapeutic Goods (Standard for Blood and Blood Components) (TGO 102) Order 2019.
Note: TGO 102 is published on the Federal Register of Legislation at www.legislation.gov.au.
TGO 108 means the Therapeutic Goods (Standard for Human Cell and Tissue Products—Donor Screening Requirements) (TGO 108) Order 2021.
Note: TGO 108 is published on the Federal Register of Legislation at www.legislation.gov.au.
Therapeutic Goods Administration or TGA means that part of the Department known as the Therapeutic Goods Administration.
TMF Guideline means the Guideline for the Preparation of Technical Master Files for Blood, Blood Components and Haematopoietic Progenitor Cells (Third Edition, 2008), published by the Therapeutic Goods Administration, as in force or existing at the commencement of this instrument.
Note: The TMF Guideline is published on the TGA website at www.tga.gov.au.
Part 2—Manufacturing principles
6 Manufacturing principles—therapeutic goods other than blood, blood components, haematopoietic progenitor cells etc.
The manufacturing principles in Part 1 of Schedule 1 are to be observed in the manufacture of therapeutic goods, including active pharmaceutical ingredients and sunscreens, for use in humans, other than the therapeutic goods specified in paragraphs 7(a) to (d).
7 Manufacturing principles—therapeutic goods that are blood, blood components, haematopoietic progenitor cells and biologicals that do not contain live animal cells, tissues or organs
The manufacturing principles in Part 2 of Schedule 1 are to be observed in the manufacture of the following therapeutic goods for use in humans:
(a) biologicals that do not comprise or contain:
(i) live animal cells; or
(ii) live animal tissues; or
(iii) live animal organs;
(b) blood;
(c) blood components;
(d) haematopoietic progenitor cells.
Note 1: The manufacturing principles to be observed in the manufacture of biologicals that comprise or contain live animal cells, tissues or organs are those set out in Part 1 of Schedule 1 (and not those set out in Part 2 of Schedule 1).
Note 2: Plasma is a blood component, see section 4 for definitions of blood components and plasma.
Part 3 – Application
8 Application
(1) The amendment of this instrument made by item 1 in Schedule 1 to the Therapeutic Goods (Manufacturing Principles) Amendment Determination 2024 applies in relation to therapeutic goods manufactured on or after 3 June 2024.
(2) Despite subsection (1), the amendment of this instrument made by item 1 in Schedule 1 to the Therapeutic Goods (Manufacturing Principles) Amendment Determination 2024, only to the extent that the amendment has the effect of incorporating Annex 16 of the PIC/S Guide to GMP, applies to therapeutic goods manufactured on or after 3 September 2024.
Schedule 1—Manufacturing Principles
Note: See sections 6 and 7.
Part 1—Therapeutic goods other than blood, blood components, haematopoietic progenitor cells etc.
(1) The manufacture of therapeutic goods to which this Part applies must comply with applicable procedures and requirements in the PIC/S Guide to GMP.
(2) Where the PIC/S Guide to GMP provides that a procedure or requirement ‘should’ be followed, the manufacture of therapeutic goods must follow the procedure or requirement in order to comply with the PIC/S Guide to GMP unless, in relation to that particular procedure or requirement:
(a) the manufacturer demonstrates, to the satisfaction of a relevant officer, that the failure to adopt that procedure or requirement:
(i) will not increase the risk that the therapeutic goods manufactured will, or could, cause harm or injury to any person, or will, or could, potentially have the effect of causing or contributing to such harm or injury; and
(ii) will not increase the risk of those therapeutic goods failing to comply with an applicable standard or relevant condition of registration, listing or inclusion; and
(iii) will not depart from any applicable record keeping requirements contained in the PIC/S Guide to GMP; or
(b) where an alternative to the procedure or requirement set out in the PIC/S Guide to GMP has been adopted—the manufacturer demonstrates, to the satisfaction of a relevant officer, that:
(i) the alternative will not increase the risk that the therapeutic goods manufactured will, or could, cause harm or injury to any person or will, or could, potentially have the effect of causing or contributing to such harm or injury; and
(ii) the alternative will not increase the risk of those therapeutic goods failing to comply with an applicable standard or relevant condition of registration, listing or inclusion; and
(iii) will not depart from any applicable record keeping requirements contained in the PIC/S Guide to GMP.
(3) The reference to “applicable procedures and requirements” in subsection (1) does not include a procedure or requirement specified in an Annex to the PIC/S Guide to GMP that is identified as voluntary.
Part 2—Therapeutic goods that are blood, blood components, haematopoietic progenitor cells and biologicals that do not contain live animal cells, tissues or organs
(1) The manufacture of therapeutic goods to which this Part applies must comply with applicable procedures and requirements in the Australian Code of Good Manufacturing Practice.
(2) Where the Australian Code of Good Manufacturing Practice provides that a procedure or requirement ‘should’ be followed, the manufacture of therapeutic goods in Australia must follow the procedure or requirement in order to comply with the Australian Code of Good Manufacturing Practice.
(3) An application for a licence to carry out steps in the manufacture of blood, blood components or haematopoietic progenitor cells must include a technical master file in relation to those goods (the relevant technical master file).
(4) Blood, blood components and haematopoietic progenitor cells must be manufactured in a manner consistent with the relevant technical master file.
(5) A blood processing plant that processes plasma collected from donors in Australia for products that are, or will be, used in Australia (the Australian product) may only be used to process plasma collected from a source outside Australia if, for that source:
(a) a plasma master file prepared in accordance with the requirements of the PMF Guideline has been submitted to a relevant officer by the licence holder of the blood processing plant; and
(b) a relevant officer has advised the licence holder of the plant that, based on the plasma master file submitted for those goods, and having taken into account the processes of the plant, the plasma from the source outside Australia will not contaminate the Australian product with any blood borne pathogens.
(6) The failure of a manufacturer of therapeutic goods to which this Part applies, to follow an applicable procedure or requirement set out in the Australian Code of Good Manufacturing Practice will constitute a failure to comply with the Australian Code of Good Manufacturing Practice unless, in relation to that particular procedure or requirement:
(a) the manufacturer demonstrates, to the satisfaction of a relevant officer, that the failure to adopt that procedure or requirement:
(i) will not increase the risk that the therapeutic goods manufactured will, or could, cause harm or injury to any person, or will, or could, potentially have the effect of causing or contributing to such harm or injury; and
(ii) will not increase the risk of those therapeutic goods failing to comply with an applicable standard or relevant condition of registration or inclusion; and
(iii) will not depart from any applicable record keeping requirements contained in the Australian Code of Good Manufacturing Practice; or
(b) where an alternative to the procedure or requirement set out in the Australian Code of Good Manufacturing Practice has been adopted—the manufacturer demonstrates, to the satisfaction of a relevant officer, that:
(i) the alternative will not increase the risk that the therapeutic goods manufactured will, or could, cause harm or injury to any person, or will, or could, potentially have the effect of causing or contributing to such harm or injury; and
(ii) the alternative will not increase the risk of those therapeutic goods failing to comply with an applicable standard or relevant condition of registration or inclusion; and
(iii) will not depart from any applicable record keeping requirements contained in the Australian Code of Good Manufacturing Practice.
