Therapeutic Goods Order No. 94 (Standard for Haematopoietic Progenitor Cells derived from Cord Blood) 2017

The central concept is the “standard” as defined in the Therapeutic Goods Act. Under that Act, a standard includes requirements relating to the quality, safety, composition, packaging, labelling, storage or distribution of therapeutic goods. This order designates certain matters as the standard for cord blood haematopoietic progenitor cells. The key definition is “haematopoietic progenitor cells”, which the order defines as 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. This is a biological definition that distinguishes these cells from other stem cell types. The scope is limited to cells derived from cord blood, which is defined as the blood remaining in the human placenta and umbilical cord after clamping. The order explicitly excludes bone marrow, peripheral blood, cord blood that is processed beyond minimal manipulation, and any tissue other than cord blood. “Minimal manipulation” is not defined in the order, which creates interpretive risk: manufacturers must assess whether their processing steps go beyond minimal manipulation. If they do, the order does not apply, and the goods may fall under a different regulatory regime (likely the biologicals regulatory framework under Part 3 2A of the Therapeutic Goods Act). Another key concept is the incorporation by reference of the NetCord-FACT International Standards, Sixth Edition. The order provides that the requirements in those private standards are the minimum requirements for manufacture. The order also includes a transition period, defined as the period from commencement (30 September 2017) to 30 September 2018. During that period, the former standard (TGO 75) continues to apply to cells collected before or during the transition period. Importantly, the transition period is for manufacturing only: if cells were collected even after the transition period ends, the new standard applies. The concept of “manufacture” is used but not defined in the order; it takes its meaning from the Act, which defines manufacture broadly to include all steps in production, including collection, processing, testing, storage and release. The order does not define “processing beyond minimal manipulation”, which is a term of art in cell therapy regulation. This gap means manufacturers must look to TGA guidance or other instruments for that definition, increasing compliance uncertainty.

The order directly affects any person or entity that manufactures therapeutic goods consisting of haematopoietic progenitor cells derived from cord blood for supply in Australia. This includes public and private cord blood banks, hospitals that collect and process cord blood for transplantation, and any company that imports such goods for supply. It also affects researchers who produce cord blood cells for clinical trials that meet the definition of therapeutic goods, though clinical trial exemptions may apply under the Act. The order indirectly affects clinicians who prescribe or administer these products, because it determines what products are lawfully available. Patients who receive cord blood transplants are ultimately affected by the quality and safety standards, but the order does not confer any direct patient rights or duties. The order affects competitors differently. Large cord blood banks that already have NetCord-FACT accreditation face minimal additional compliance cost; the order simply codifies what they already do. Smaller operators or new entrants who have not invested in accreditation must either become compliant with the private standards or exit the market, unless they can self certify and convince regulators. The transitional arrangement provides a one year window during which cell collections under the old standard may still be used, which softens the impact for existing stocks. However, for new collections after 30 September 2018, the stricter NetCord FACT Sixth Edition requirements apply. The exclusion of bone marrow, peripheral blood and cord blood processed beyond minimal manipulation means that manufacturers of those products are unaffected by this order. For manufacturers of minimally manipulated cord blood only, compliance involves implementing the full NetCord FACT standards across facility, equipment, personnel, quality management, donor screening, collection, processing, testing, cryopreservation, storage, labelling and release. The order also affects the Foundation for the Accreditation of Cellular Therapy (FACT) and NetCord indirectly: their private standard has been given legal force in Australia, which may increase demand for accreditation services and consulting, but also exposes them to regulatory scrutiny if the standard is updated. The order does not affect patients directly as a matter of legal duty, but it shapes the safety and availability of cord blood products.

The order imposes only one substantive duty: manufacturers of cord blood haematopoietic progenitor cells must ensure that the manufacture meets the minimum requirements of the NetCord FACT International Standards, Sixth Edition. This duty is not absolute in the sense that the order does not say “must comply”. Instead it says “the requirements provided in the NetCord FACT International Standards are specified as minimum requirements for the manufacture”. That language is likely intended to be mandatory: the standard itself is the benchmark, and failure to meet it means the goods do not comply with the standard, which affects their eligibility for inclusion in the Australian Register of Therapeutic Goods (ARTG). The actual legal duty arises from the Therapeutic Goods Act: therapeutic goods must comply with any applicable standard to be imported, exported, manufactured or supplied. The order thus provides the content of that standard. The order does not create any rights for patients, consumers or third parties. There is no private right of action for breach of the standard. Enforcement is through the TGA’s regulatory powers. The order also does not grant any rights to manufacturers, such as the right to use the NetCord FACT standard as a defence; it only imposes obligations. The transitional arrangement under section 8 creates a limited right to continue using the former standard for cells collected before or during the transition period. That is a relieving provision: it allows manufacturers to avoid immediate re compliance for existing inventory. However, it is conditional on the cells being collected before or during the transition period, and manufacturing must occur during that period. The order does not specify what happens if a manufacturer fails to meet the NetCord FACT requirements but still meets the old standard; that would be non compliance if the cells were collected after the transition period ends. The order also implicitly grants manufacturers the freedom to choose how to meet the NetCord FACT standards, including whether to seek accreditation or self certify. That is a significant feature: the order does not mandate accreditation, only that the requirements be met. This allows smaller operators to comply without paying accreditation fees, though they may face higher inspection scrutiny. The order does not address the scenario where the NetCord FACT standards are updated after July 2016. Because the order specifies that edition “as in force at that time”, any later revision would not automatically become the Australian standard; a new TGO would be needed. That provides regulatory stability but may cause the standard to become out of date if the private standard advances.

The order itself does not prescribe penalties. Penalties for non compliance with a therapeutic goods standard are found in the Therapeutic Goods Act 1989. Under that Act, it is an offence to manufacture, import, export or supply therapeutic goods that do not comply with an applicable standard. The maximum penalties include imprisonment for individuals and significant fines for corporations. For example, section 22 of the Act makes it an offence to supply goods that are not entered in the ARTG, and section 16 requires compliance with standards as part of registration or listing. The TGA can also issue infringement notices, cancel or suspend registration, and seize non compliant goods. The order sets the substantive standard that the TGA will enforce. Enforcement risk is highest for manufacturers that collect cord blood after 30 September 2018 and do not adopt the NetCord FACT Sixth Edition requirements. The transitional period provides a safe harbour for cells collected earlier. Manufacturers who self certify must be able to demonstrate compliance if audited. The TGA conducts inspections under the Manufacturing Principles, and non compliance with the standard could lead to a finding that the goods are not manufactured in accordance with good manufacturing practice. The use of a private standard also introduces enforcement ambiguity: if a manufacturer disputes whether it meets the NetCord FACT requirements, the TGA may need to interpret an external document. The NetCord FACT standards include interpretive language and may be updated. Since this order adopts a static version, any gap between current practices and the 2016 version could be enforced even if more recent standards are more lenient in some respects. The order does not provide for any remedial steps or defences beyond the transitional arrangement. There is no provision for a manufacturer to apply for a variation or exemption; any such mechanism would be under the Act. Manufacturers should be aware that the TGA can also take compliance action against directors and officers under the Act’s executive liability provisions.

This order sits within a broader regulatory framework for therapeutic goods. It is made under the Therapeutic Goods Act 1989 and must be read together with that Act’s provisions on standards, registration, listing, manufacturing principles and post market monitoring. The order interacts with the Australian Regulatory Guidelines for Biologicals, which apply to cell and tissue products. Because this order only covers minimally manipulated cord blood, products that are processed beyond minimal manipulation are regulated under the biologicals framework or as medicines. The line between minimal and more than minimal manipulation is critical and is not defined in this order. That definition comes from the Act or TGA guidance, such as the Australian Code of Good Manufacturing Practice for Human Blood and Blood Components and the Guidance on the Regulation of Cellular Therapies. The order also interacts with state and territory legislation on human tissue donation, such as the Human Tissue Act in various states, which governs consent for cord blood collection. Donor consent and screening requirements are partly addressed by the NetCord FACT standards, which include donor eligibility criteria. The order does not override tissue donation laws; it supplements them. The order’s reference to the NetCord FACT standards incorporates a private international standard that may conflict with Australian guidelines. For example, the FACT standards may diverge from the Therapeutic Goods Act’s Manufacturing Principles in some details. In such cases, the manufacturer must comply with both: the order’s standard is a minimum, but the Act’s other requirements may impose additional obligations. The order does not prevail over the Act; it is subordinate legislation. The order repeals the previous Therapeutic Goods Order No. 75, which had its own standard. For cells collected before the transition period, the old standard still applies, so both orders effectively operate in parallel for a time. Interactions with customs and quarantine laws are indirect: imported cord blood must comply with the standard to be imported under the Act. The order also interacts with the Privacy Act 1988 to the extent that donor information is handled. The incorporation of the FACT standards means manufacturers may also need to comply with international accreditation requirements that extend beyond Australian law, such as US FDA or EU standards, if they wish to export.

This order is the original instrument made on 26 September 2017 and commenced on 30 September 2017. There is no amendment history because it has not been amended. The order replaced Therapeutic Goods Order No. 75, which was made on 1 August 2007 and registered as F2007L03598. The previous standard was repealed in full upon commencement of this order, subject to the transitional arrangements. The order itself may be amended by a later order under subsection 10(1) of the Act. Because it incorporates the NetCord FACT Sixth Edition as at July 2016, any future revision of that private standard would not automatically amend this order. To update the standard, the Minister’s delegate would need to make a new order or vary this one. The Legislation Act 2003 requires that incorporating documents be identified as in force at a particular date, and this order complies by stating “as in force at that time”. The order is a disallowable legislative instrument and was tabled in Parliament. It is subject to potential disallowance within 15 sitting days, although no disallowance motion has been recorded. The order has remained unchanged for over six years, which may indicate either regulatory stability or stagnation, depending on how quickly the field evolves. Cord blood processing techniques have advanced since 2016, and the NetCord FACT Seventh Edition (published 2021) is now in effect internationally, but Australia still uses the 2016 edition. This creates a risk that Australian manufacturers must meet a standard that is less current than what international competitors follow, which could affect quality claims or trade. Conversely, it also means Australian regulations are not hostage to private standard updates that might increase costs. The lack of amendment simplifies compliance for manufacturers who have already documented against the 2016 version.

There is no reported litigation specifically interpreting this order, and none is expected given its narrow technical scope. The order is a legislative instrument that sets a standard; disputes about the standard would likely arise in the context of TGA compliance actions or judicial review of decisions to refuse registration or cancel listing. No cases involving the predecessor TGO 75 appear in the public record either. The lack of litigation suggests the standard is accepted by industry and that compliance is largely uncontroversial. However, the potential for future litigation arises from the phrase “processed beyond minimal manipulation”. That phrase is not defined in the order, and its interpretation could be contested in a dispute between a manufacturer and the TGA over whether a particular process is minimally manipulated or not. Courts would likely look to TGA guidance and international practice. Another potential source of litigation is the incorporation of the private NetCord FACT standards. If the standard is unclear or applied inconsistently, a manufacturer might argue that the TGA misinterpreted the standard or that the standard itself is invalid because it was not properly incorporated or because it delegates legislative power impermissibly. That argument has not been tested. In general, challenges to therapeutic goods standards are rare because they are highly technical and the industry prefers to cooperate rather than litigate. The order itself does not create any private rights, so class actions or consumer claims are unlikely. Any enforcement action by the TGA would be administrative or criminal, and a manufacturer could defend on the basis that its goods meet the standard. Litigation would likely centre on factual questions of what the NetCord FACT standards require and whether the manufacturer met them, rather than on the validity of the order.

The most significant trap is the absence of a definition for “minimal manipulation”. A manufacturer that processes cord blood beyond minimal manipulation (e.g., culture expansion, selection, genetic modification) may assume this order applies, but in fact it does not, and the goods would need to comply with a different regulatory pathway, such as the biologicals framework. Misclassifying the product could lead to supply of unapproved goods. Conversely, a manufacturer that assumes its product is exempt because it is minimally manipulated but then performs a step that crosses the line may find itself outside the order without realising. The transition period also has a hidden nuance: it applies to cells “collected before or during the transition period”. If collection occurs after 30 September 2018, the new standard applies even if the cells are not manufactured into a final product until later. Banks with a large inventory of cells collected before October 2018 can continue using the old standard for manufacture during the transition year, but once that year ends, any manufacturing of those cells must comply with the new standard. The wording of section 8(2) says “manufacture” during the transition period, but cells collected before or during that period can be manufactured after the period ends? The provision is ambiguous. It says the former standard continues to apply for the duration of the transition period in relation to manufacture if the cells were collected before or during the transition period. That seems to limit the application of the old standard to manufacturing that occurs within the transition period. After the transition period ends, the old standard no longer applies; then the new standard applies regardless of when cells were collected. That would mean any cells collected before or during the transition period but not manufactured into a final product before 30 September 2018 would have to meet the new standard. This could catch cord blood banks that collect units but do not process them for several months. The incorporation of the NetCord FACT standard by reference also creates a gotcha: the standard is available for free download, but it is a lengthy document (over 200 pages). It includes requirements that may not be immediately obvious, such as detailed facility specifications, quality management system requirements, and chain of identity procedures. A manufacturer that only reads the order will miss these. Also, the order specifies the Sixth Edition as at July 2016. If a manufacturer follows the Seventh Edition (2021) thinking it is more modern, they may be complying with a different version that is not the legal standard. The order’s failure to define “manufacture” means the broad definition in the Therapeutic Goods Act applies, which includes transport and distribution. Outsourcing any step may require a separate manufacturing licence that also complies. Finally, the order does not address what happens if the NetCord FACT standard conflicts with an Australian standard or guideline. In such a case, the manufacturer must meet both unless the Act provides otherwise, potentially needing to satisfy the higher requirement.

Compliance with this order requires a manufacturer to ensure that the manufacture of cord blood haematopoietic progenitor cells meets the minimum requirements of the NetCord FACT International Standards, Sixth Edition. The first step is to obtain a copy of those standards, available from the FACT website. The manufacturer must then conduct a gap analysis comparing its current practices against each requirement. The standards cover facility design, equipment qualification, personnel qualifications and training, donor eligibility including consent and medical history screening, collection procedures, processing methods, testing (microbiology, sterility, potency, cell count), cryopreservation, storage conditions, transport, labelling, record keeping, adverse event reporting, and quality management. The manufacturer should document compliance in a quality manual and batch records. It is critical to confirm that the product is indeed within scope: only minimally manipulated cord blood HPCs. If any step goes beyond minimal manipulation, this order does not apply and the manufacturer must follow the biologicals or medicines framework. For borderline processes, manufacturers should seek a written classification from the TGA via the biologicals advisory process. The next step is to decide whether to seek NetCord FACT accreditation. Accreditation is not legally required, but it provides a presumption of compliance and is often demanded by hospitals for transplant products. Accreditation involves a formal application, inspection and fee. Self certification is possible but risky: the manufacturer bears the burden of proving compliance in an audit. The manufacturer must also ensure that any collection of cord blood complies with relevant state human tissue laws and that donors give informed consent. The transitional arrangements should be used to manage inventory: cells collected before 30 September 2018 can be manufactured under the old TGO 75 if manufacturing occurs within that window. After that, all manufacturing must meet TGO 94. Manufacturers should label and segregate inventory by collection date to ensure only eligible cells are manufactured under the transitional rules. Documentation should clearly show when each unit was collected and when it was processed. Finally, the manufacturer must comply with all other requirements of the Therapeutic Goods Act, including listing or registration on the ARTG if the goods are to be supplied commercially. The order sets the standard, but the Act requires that the goods meet that standard as a condition of entry. Regular internal audits and annual reviews against any updates to the NetCord FACT standard (even though not yet adopted) can help maintain readiness for future amendments. Consulting a regulatory affairs specialist with cell therapy experience is advisable given the technical complexity. The order does not itself require reporting to the TGA, but the Act does; any adverse events must be reported to the TGA under the medical device or biologicals adverse event reporting system.