Therapeutic Goods Act 1989
Therapeutic Goods (Manufacturing Principles)
Determination No. 1 of 2013
MP1/2013
I, John Skerritt, delegate of the Minister for Health for the purpose of section 36 of the Therapeutic Goods Act 1989 and acting under subsection 36(1) of that Act hereby:
(1)      revoke the following instruments:
·               Therapeutic Goods (Manufacturing Principles) Determination No. 1 of 2007
·               Therapeutic Goods (Manufacturing Principles) Determination No. 1 of 2009; and
(2)      determine the following principles to be observed in the manufacture of therapeutic goods for use in humans, as set out in this Determination.
 
Dated  20th day of May 2013
 
 (Signed by)
John Skerritt
Delegate of the Minister for Health
Citation
1.      This Determination may be cited as the Therapeutic Goods (Manufacturing Principles) Determination No. 1 of 2013.
Commencement
2.      This Determination commences on 31 May 2013.
[Note: see Legislative Instruments Act 2003 section 12.]
Application
3.      The manufacturing principles applicable to specific therapeutic goods are set out in the following Divisions:
a.         Division 1 – Therapeutic Goods including Active Pharmaceutical Ingredients (API) and Sunscreens, but not Blood, Blood Components, Biologicals, Plasma, Haematopoietic Progenitor Cells, Therapeutic Devices and Medical Devices
b.         Division 2 –Blood, Blood Components, Biologicals, Plasma and Haematopoietic Progenitor Cells
c.         Division 3 – Therapeutic Devices
Interpretation
4.      In this Determination, unless the contrary intention appears:
“active pharmaceutical ingredients (API)” means any substance or mixture of substances intended to be used in the manufacture of a medicine and that, when used in the production of a medicine, becomes an active ingredient of that medicine.  These substances are 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.
“AS ISO 13485-2003” means the document entitled “AS ISO 13485-2003 Medical devices – Quality management systems – Requirements for Regulatory purposes published by the International Standards Organisation.
“biological” has the same meaning as in the Act.
“blood” means whole blood collected from a single human donor and processed either for transfusion or further manufacturing.
“blood components” means therapeutic components of blood (red cells, white cells, platelets, plasma) that can be prepared by centrifugation, filtration and freezing, but not including haematopoietic progenitor cells.
“EN 556” means the document entitled EN 556: 1994 “Sterilization of medical devices – requirements for medical devices to be labelled ‘Sterile’, published by the European Standards Committee (CEN) Central Secretariat.
“haematopoietic progenitor cells” means cells that are primitive multipotent cells capable of self-renewal as well as differentiation and maturation into all haematopoietic lineages, used for haematopoietic reconstitution.
“medicine” has the same meaning as in the Act.
“plasma” means plasma, separated from human donor blood, intended for a number of purposes including the production of further blood components, the production of which is  required to be licensed under Chapter 3, Part 3-3 of the Act.
“Register” has the same meaning as in the Act.
“standard” has the same meaning as in the Act.
 “the Act” means the Therapeutic Goods Act 1989, as amended from time to time.
“the Australian Code of Good Manufacturing Practice” means the document titled: “Australian Code of Good Manufacturing Practice for Human Blood, Blood Components, Human tissues and Human cellular therapy products” dated April 2013 and published by the TGA on its website.
[Note: Clause 14 provides transitional arrangements in relation to the application of the Australian Code of Good Manufacturing Practice between the commencement of this Determination and up to and including 31 May 2014].
“the Code” means the document titled “PIC/S Guide for Good Manufacturing Practice for Medicinal Products – 15 January 2009”, PE 009-8, published by the Pharmaceutical Inspection Convention and Pharmaceutical Inspection Co-operation Scheme (jointly referred to as PIC/S), dated 15 January 2009, except for the following Annexes of that document:
a.         Annex 4 (titled Manufacture of Veterinary Medicinal Products Other than Immunologicals); and
b.         Annex 5 (titled Manufacture of Immunological Veterinary Medicinal Products); and
c.         Annex 14 (titled Manufacture of Products Derived from Human Blood or Human Plasma) of that document.
“Technical Master File”, for a therapeutic good, means:
compilations of scientific and technical data provided by a manufacturer which include a description of the steps of manufacture that is consistent with the description of steps of manufacture identified in the document entitled "Guideline for the Preparation of Technical Master Files for Blood, Blood Components and Haematopoietic Progenitor Cells", published by the TGA on its website; and
b.      detailed scientific and technical data or information that must satisfy the Secretary that:
the blood or blood components, manufactured using the steps of manufacture mentioned in paragraph (a), will meet Therapeutic Goods Order No. 81 – Standards for Blood and Blood Components; or
the haematopoietic progenitor cells derived from cord blood manufactured using the steps of manufacture mentioned in paragraph (a) will meet Therapeutic Goods Order No. 75 - Standard for Haematopoietic Progenitor Cells derived from Cord Blood; and
donor selection, testing and the process for minimising infectious disease transmission via therapeutic goods that are human blood and blood components will meet the requirements of Therapeutic Goods Order No. 88 - Standards for donor selection, testing and minimising infectious disease transmission through therapeutic goods that are human blood and blood components, human tissues and human cellular therapy products.
“Therapeutic device” has the same meaning as in the Act.
“TGA” means the Therapeutic Goods Administration, a business unit of the Department of Health and Ageing.
Division 1 – Manufacturing principles for therapeutic goods including Active Pharmaceutical Ingredients (API) and Sunscreens, but not Blood and Blood Components, Biologicals, Plasma, Haematopoietic Progenitor Cells therapeutic devices and medical devices.
(1)          This Division applies to the manufacture of therapeutic goods including API and Sunscreens, other than:
(a)      blood and blood components, plasma and haematopoietic progenitor cells;
(b)     biologicals;
(c)      therapeutic devices;
(d)     medical devices.
(2)          Subject to subclause (3), manufacturers of therapeutic goods in Australia to which this Division applies must follow the procedures and requirements set out in Part One of the Code, and in addition, each of the Annexes to the Code that apply to the particular therapeutic goods being manufactured. 
(3)          Where the Code provides that a procedure or requirement ‘should’ be followed, manufacturers of therapeutic goods in Australia must follow that procedure or requirement in order to comply with the Code, unless in  relation to that particular procedure or requirement:
(a)      the manufacturer demonstrates, to the satisfaction of the TGA, that the failure to adopt that procedure or requirement:
                                                  i.      will not increase the risk that the goods produced as a result 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; and
                                                ii.      will not increase the risk of the therapeutic goods in question failing to comply with, where applicable both the standard for that therapeutic good and the conditions of the listing or registration for that therapeutic good; and
                                              iii.      will not depart from  the record keeping requirements contained in the Code; or
(b)     where an alternative procedure to the procedure or requirement set out under an applicable Part of, or Annex to, the Code has been adopted, the manufacturer demonstrates, to the satisfaction of the TGA, that:
                                                  i.      the alternative procedure will not result in the production of therapeutic goods that could increase the risk of harm or injury to any person or will or could  potentially have the effect of causing or contributing to such harm; and
                                                ii.      the alternative procedure will not increase the risk of the therapeutic goods in question failing to comply with, where applicable, both the standard for that therapeutic good and the conditions of the listing or registration; and
                                              iii.      will not depart from  the record keeping requirements contained in the Code.
(4)          For the purposes of subclause (2), the word “apply” does not include the application, to particular therapeutic goods being manufactured, of an Annex that is stated in the Code to be ‘voluntary’.
 
Division 2 – Manufacturing principles for Blood, Blood Components, Plasma, Biologicals and Haematopoietic Progenitor Cells
(5)          This Division applies to the manufacture of blood, blood components, plasma, biologicals and haematopoietic progenitor cells.
(6)          A manufacturer of blood, blood components, plasma and haematopoietic progenitor cells must lodge a Technical Master File with an application for a licence under Chapter 3, Part 3-3 of the Act.
(7)          Blood, blood components, plasma and haematopoietic progenitor cells must be manufactured:
(a)    in compliance with applicable requirements of the Australian Code of Good Manufacturing Practice; and
(b)   in a manner consistent with the relevant Technical Master File lodged for the goods with the TGA by the manufacturer.
(8)          Biologicals must be manufactured in compliance with applicable requirements of the Australian Code of Good Manufacturing Practice.
(9)          Where the Australian Code of Good Manufacturing Practice provides that a procedure or requirement ‘should’ be followed, manufacturers of therapeutic goods in Australia must follow that procedure or requirement in order to comply with the Australian Code of Good Manufacturing Practice.
(10)      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 European Agency for the Evaluation of Medicinal Products document entitled "Guideline on the scientific data requirements for a plasma master file (PMF) EMEA/CPMP/BWP/3794/03, revision 1(2006)" has been submitted to the Secretary by the licensee of the relevant blood processing plant; and
(b)   the Secretary has advised the licensee of the plant that, based upon the plasma master file submitted for those goods, and having taken into account the plant's processes, the plasma from the source outside Australia will not contaminate the Australian product with any blood borne pathogens.
(11)      The failure of a manufacturer in Australia of therapeutic goods, to which this Division applies, to follow a particular procedure or requirement set out in an applicable Part of 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 the TGA, that the failure to adopt that procedure or requirement:
                                       i.      will not increase the risk that the goods produced as a result 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; and
                                     ii.      will not increase the risk of the therapeutic goods in question failing to comply with, where applicable, both the standard for that therapeutic goods and to the conditions of registration for that therapeutic good; 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 procedure to the procedure or requirements set out under and applicable part of the Australian Code of Good Manufacturing Practice has been adopted, the manufacturer demonstrates, to the satisfaction of the TGA, that:
                                       i.          the alternative procedure will not increase the risk that the goods produced as a result 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; and
                                     ii.          the alternative procedure will not increase the risk of the therapeutic goods in question failing to comply with, where applicable, both the standard for that therapeutic goods and the conditions of  registration for that therapeutic good; and
                                   iii.          will not depart from the record keeping requirements contained in the Australian Code of Good Manufacturing Practice.
 
Division 3 – Therapeutic Devices
(12)      In this Division, the following therapeutic devices must be manufactured in compliance with an approved quality assurance system as follows:
(a)      for a therapeutic device, other than a device incorporating human tissue
                                       i.          if the therapeutic device must be listed in the Register, it must be manufactured in compliance with AS ISO 13485-2003 other than clause 7.3 (Design and Development); or
                                     ii.          if the therapeutic device must be registered in the Register , it must be manufactured in compliance with AS ISO 13485-2003; and
                                   iii.          if the therapeutic device is labelled ‘Sterile”, it must also be manufactured in compliance with EN 556.
Transitional arrangements for goods mentioned in Division 2
(13)      From the commencement of this Determination up to and including 31 May 2014 (the transition period), where Division 2 of this Determination requires a manufacturer to comply with the Australian Code of Good Manufacturing Practice:
(a)   a manufacturer may choose to comply with either:
                                  i.          the requirements of the document titled: “Australian Code of Good Manufacturing Practice for Human Blood and Tissues” published in the Commonwealth of Australia Gazette, No. S 518, Thursday, 28 September 2000; or

                                ii.          the requirements of both:
a.       The document titled: “Australian Code of Good Manufacturing Practice for Human Blood, Blood Components, Human Tissues and Human Cellular Therapy products ”; dated April 2013 (published by the TGA on its website),  and
b.      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; and
Note 1: 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 will apply, from 31 May 2014, to human blood and blood components, human tissues and cellular therapy products that are collected from a donor, or subjected to any other manufacture, on or after 31 May 2014.  Before 31 May 2014, compliance with Therapeutic Goods Order No.88 is voluntary.
Note 2:  If a person wishes to begin complying with the Australian Code of Good Manufacturing Practice (2013) before 31 May 2014, the person must also ensure that the requirements of Therapeutic Goods Order No. 88 is or has been observed in the manufacture of their goods, as these are intended to apply together.
(b)   during the transition period, a reference in this Determination to the Australian Code of Good Manufacturing Practice means the document or documents with which the manufacturer has chosen to comply, being either the document referred to in subparagraph (i) of this clause or the documents referred to in subparagraph (ii) of this clause.
(14)      To avoid doubt, after 31 May 2014, where this Determination requires a manufacturer to comply with the Australian Code of Good Manufacturing Practice, a manufacturer must comply with the requirements of the document titled: “Australian Code of Good Manufacturing Practice for Human Blood, Blood Components, Human Tissues and Human Cellular Therapy products” dated April 2013 (published by the TGA on its website).
Note:  From 31 May 2014, 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 will also apply and manufacturers must comply with this Order.