To respond to queries in relation to evaluation of Technical Master Files (TMF), the TGA would like to clarify the product standards that apply to haematopoietic progenitor cells (HPCs). The TGA regulates therapeutic goods in accordance with the Therapeutic Goods Act 1989 (the Act), and relevant legislative instruments. The Act defines "therapeutic goods" as meaning goods for therapeutic use, for use as an ingredient or component in manufacture of therapeutic goods, or for use as a container or part of a container for the former.
Section 14 and 14A of the Act requires that therapeutic goods which are imported into Australia, supplied for use in Australia or exported from Australia, conform with a standard applicable to the goods. The Act defines "standard", in relation to therapeutic goods, as a standard that is either specified in an order under section 10 of the Act, or if no such order is applicable to the goods but the goods are the subject of a monograph in any of the British Pharmacopoeia (BP), European Pharmacopoeia (Ph. Eur.), and United States Pharmacopoeia-National Formulary (USP), then the standard is constituted by the statements contained in that monograph.
There are therapeutic goods standards specified in orders made under section 10 of the Act. In the case of HPCs manufactured from cord blood the standard is specified in Therapeutic Goods Order No. 94 (Standard for Haematopoietic Progenitor Cells derived from Cord Blood. For non-cord blood HPCs, or ingredients or components used in the manufacture of cord and non-cord HPCs, there is no specific order specifying a standard for these goods and thus the BP, Ph. Eur. and the USP are the default standards.
Within the HPC sector, manufacturers are encouraged to maintain a dialogue with the TGA in relation to their manufacturing requirements and, if requested, this could include a pre-submission meeting or teleconference. In addition, the TGA is apprising manufacturers of their regulatory requirements during evaluation of their TMFs. Depending on the specific activities undertaken by a manufacturer, relevant standards from the pharmacopoeias may include, but are not limited to:
- Human Haematopoietic Stem Cells (Ph. Eur. monograph 2323)
- Appendix XIV C. Test for Bacterial Endotoxins (LAL Test) (Ph. Eur. method 2.6.14)
- SC I C. Bacterial Endotoxin Testing
- Appendix XVI A. Test for sterility (Ph. Eur. method 2.6.1)
- Appendix XVI E. Microbiological control of cellular products (Ph. Eur. method 2.6.27)
- Dimethyl sulfoxide (Ph Eur monograph 0763)
- Appendix XIV N. Numeration of CD34/CD45+ cells in haematopoietic products (Ph. Eur. method 2.7.23)
- Dextran 40 for injection (Ph. Eur. monograph 0999)
- Dextran 40 for intravenous infusion (BP 2009 volume III)
- Appendix XIV N 2. Colony-forming cell assay for human haematopoietic progenitor cells (Ph. Eur. method 2.7.28)
Detailed information regarding the default standards, including the current edition of the pharmacopoeias, is available at: Questions & answers relating to the additional default standards legislation.
Please do not hesitate to contact the TGA if you require further advice or guidance regarding the requirements of the default standards in relation to the regulation of HPCs.