Summary of the human cell and tissue therapies framework
15 July 2009
The Australian Health Ministers' Conference (AHMC) agreed to the regulatory framework for Human Cell and Tissue Therapies proposed to it in November 2006 by the Therapeutic Goods Administration. However, it recommended that organs and un-manipulated reproductive tissues (for Assisted Reproductive Technology) be subject to further detailed analysis and deliberations before making a decision regarding their inclusion in Class 1 of the framework. In July 2008 AHMC agreed that there was no requirement for further regulation of un-manipulated reproductive tissues and that possible regulatory arrangements for solid organs be referred to the new national organ donation and transplantation authority.
(a) Subject matter of regulation
The agreed definition for the Human Cell and Tissue (HCT) Framework covers
- "all articles containing or consisting of, or derived from, human cells or tissues that are intended for implantation, transplantation, infusion or transfer into a human recipient"; and
- the definition of HCTs:
- excludes blood, blood components and blood products; and
- excludes secreted or excreted human product, such as hormones, human breast milk or urine; and
- may exclude other articles that may be declared from time to time in a Therapeutic Goods Order (an Order)
(b) Classification of biological products
The biologicals regulatory framework comprises four classes of biologicals with varying levels of regulation applying based on a risk-benefit analysis of the types of biologicals.
The proposed four classes will be defined as follows:
Class 1
A biological is Class 1 if:
- it is not banked; and
- it is not processed (that is, manufactured by a process other than minimal manipulation*); or
- it is declared by Order to be a Class 1 biological.
Class 2
A biological is Class 2 if:
- it is banked; and
- it is not processed (that is manufactured by a process other than minimal manipulation*); or
- it is declared by Order to be a Class 2 biological.
Class 3
A biological is Class 3 if:
- it is processed beyond minimal manipulation, in a manner that may alter the structure and properties of the cell or tissue but does not purposefully alter the biological activity; or
- it is declared by Order to be a Class 3 biological.
Class 4
A biological is Class 4 if:
- it is processed in a manner that deliberately manipulates the biological property(ies); or
- the intended use is not its homologous function; or
- it is declared by Order to be a Class 4.
* minimal manipulation means a process involving any of the following actions:
- centrifugation;
- refrigeration;
- freezing;
- trimming;
- flushing;
- washing;
- any action similar to that mentioned in paragraphs (a), (b), (c), (d), (e) or (f).
(c) Level of regulation to be applied to each class
The level of regulation applied to HCTs will be as follows:
Class 1: Declaration of compliance with relevant Standards
An applicant will be required to attest to compliance with relevant mandatory Standards, through the submission to the TGA of a Declaration. The Standards will be based on existing industry Standards.
Class 2: Compliance with Standards and Manufacturing Principles
Applicants for a Class 2 HCT cell or tissue type will be required to:
- demonstrate compliance with Manufacturing Principles. Compliance will be evidenced by the TGA issuing a Manufacturing Licence in respect of the relevant activities at the facility in which the tissue will be banked; and
- demonstrate compliance with relevant Standards for each tissue type.
If both of these requirements are met, the TGA will enter the approved tissue(s) on the ARTG.
Class 3: Compliance with Standards (and demonstration of safety, quality efficacy) and Manufacturing Principles
Applicants for a Class 3 HCT product will be required to:
- demonstrate compliance with Manufacturing Principles - as evidenced by the TGA issuing a Manufacturing Licence in respect of the relevant activities at the facility in which the cells or tissue will be manufactured; and
- demonstrate that the particular HCT is safe, efficacious and of high quality. This will require the applicant to submit a Dossier to the TGA.
If the applicant meets both of these requirements the TGA will enter the approved Class 3 cell or tissue on the ARTG.
Class 4 - As for Class 3 except more detailed data required
As for Class 3 except that the Dossier will also need to contain relevant clinical data and analysis.
(d) Exemptions and exceptions
The legislation will include exemptions from the regulatory requirements described above for:
- single medical procedures. In addition to the special exemption provisions, for example, experimental use and special access, the following medical procedures will be exempt from TGA regulation:
- single surgical procedures performed on one patient (autologous transplant) such as bone grafts and vein transplants
- single surgical procedures involving two patients (non-autologous or allotransplant) such as a haematopoietic progenitor cell or tissue donation from a live donor within the same facility as the transplant recipient.
- exceptional release/acceptance. It is proposed that the TGA will set standards that must be complied with by organisations proposing exceptional release/acceptance of HCTs (for example, cells that show evidence of a transmittable disease and when no alternative tissue or cells are available for the treatment of a life-threatening condition).
(e) Adverse events reporting
It is proposed that adverse event reporting for HCTs will rely on existing processes established within the TGA. Specific guidance will be developed in relation to HCTs to define what will need to be reported to the TGA (with advice on a voluntary or mandatory basis) and the timeframes for reporting.
(f) Implementation
During the agreed transition period of three years it is proposed that there will be a staged implementation of the new framework for currently supplied HCTs. Classes 1 and 4 will be implemented over the three year period. Submissions for Classes 2 and 3 products, establishing compliance with relevant standards or quality, safety and efficacy (as applicable) should be lodged with the TGA between 12 and 18 months following establishment of the framework with the expectation of full compliance by the end of the three year transition period.
The documents that will underpin the regulatory framework (including the Standards and the Manufacturing Principles) are continuing to be developed in consultation with stakeholders and with the advice of the Therapeutic Goods Committee and other relevant committees.
(g) General provisions
The general regulatory provisions relating to sponsors, manufacturers, products, import-export, supply, record keeping and so on will also be applicable in the regulation of HCTs.