Biologicals framework implementation
4 December 2009
Implementation of the Biologicals framework
The Australian Government has agreed to proceed with the development and implementation of a new regulatory framework, known as the Biologicals framework for human cell and tissue therapies and other emerging biological therapies.
Currently some biologicals are excluded from regulation. Others are exempt from aspects of regulation or are regulated as medicines or devices. The proposed Biologicals framework is being implemented to regulate many of these products.
The Biologicals framework excludes assisted reproductive tissues and solid organs. The possible regulatory arrangements for solid organs have been referred to the new Australian Organ and Tissue Donation and Transplantation Authority. Haematopoietic Progenitor Cells (HPC), blood and blood components may be included in the framework at a later date following further consultation with the sector.
The proposed Biologicals framework is expected to be implemented in 2010 followed by a transition period for products to move into the new scheme.
Background to the Government decision
The existing therapeutic goods regulatory framework is currently not well adapted for human cell and tissue therapies (HCTs). In response to this shortcoming, the Australian Health Ministers' Conference (AHMC) in 2002 endorsed the development of a regulatory framework for HCTs by the TGA.
In 2006 AHMC agreed to the proposed national regulatory framework (the HCT framework, now known as the Biologicals framework) with the exclusion of solid organs and assisted reproductive tissues, which required further consideration.
Subject matter of regulation – Meaning of biological
The Therapeutic Goods Amendment Bill 2009 to implement the Biologicals framework defines a biological as:
- (1) Subject to subsection (3), a biological is a thing that:
- (a) either:
- (i) comprises, contains or is derived from human cells or human tissues; or
- (ii) is specified under subsection (2); and
- (b) is represented in any way to be, or is, whether because of the way in which it is presented or for any other reason, likely to be taken to be:
- (i) for use in the treatment or prevention of a disease, ailment, defect or injury affecting persons; or
- (ii) for use in making a medical diagnosis of the condition of a person; or
- (iii) for use in influencing, inhibiting or modifying a physiological process in persons; or
- (iv) for use in testing the susceptibility of persons to a disease or ailment; or
- (v) for use in the replacement or modification of parts of the anatomy in persons.
- (a) either:
- (2) The Secretary may, by legislative instrument, specify things for the purposes of subparagraph (1)(a)(ii).
- Note: For specification by class, see subsection 13(3) of the Legislative Instruments Act 2003.
- (3) The Secretary may, by legislative instrument, determine that a specified thing is not a biological for the purposes of this Act.
- Note: For specification by class, see subsection 13(3) of the Legislative Instruments Act 2003.
Classification of biological products
The proposed Biologicals framework comprises four classes of biologicals with varying levels of regulation applying based on risk, extent of manipulation applied to the biologicals and whether the intended use is its usual biological function. Class 1 products will be low-risk products. Class 4 will be higher-risk products. All biologicals (Class 1 through 4) will be subject to inclusion on the Australian Register of Therapeutic Goods (ARTG).
The proposed definitions of the four classes are 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 biological.
* minimal manipulation means a process involving any of the following actions:
- centrifugation
- refrigeration
- freezing
- trimming
- flushing
- washing
- simple milling
- any action similar to that mentioned in paragraphs (a), (b), (c), (d), (e), (f) or (g).
banked means maintenance, under appropriate controlled conditions, in an inventory, of a finished product that has been determined suitable for supply.
Level of regulation to be applied to each class
The proposed level of regulation applied to human cell and tissue therapies and other emerging biological products 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 Class 1 product will then be entered on the ARTG.
Standards will be determined following consultation with each relevant sector.
Class 2: Compliance with Standards and Manufacturing Principles
Applicants for a Class 2 biological 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 on the ARTG.
Class 3: Compliance with Standards (and demonstration of safety, quality efficacy) and Manufacturing Principles
Applicants for a Class 3 biological 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 biological 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 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.
Exemptions from ARTG inclusion
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 provisions
It is proposed that the TGA will set requirements that must be met where it is intended to use a biological that does not meet mandatory requirements (for example, when no alternative tissue or cells are available for the treatment of a life-threatening condition). The requirements for exceptional release provisions will be subject to public consultation.
Adverse event reporting
It is proposed that adverse event reporting for biologicals will be based on existing processes established within the TGA. Specific guidance will be developed to define adverse event reporting requirements (with advice on a voluntary or mandatory basis) and the timeframes for reporting. The requirements for adverse event reporting will be subject to public consultation.
Transition arrangements
It is proposed that all currently supplied biologicals will have a 3 year transition period, from the date of implementation of the Biologicals framework, to meet the new requirements. During transition biologicals already supplied on the day of implementation will continue to be regulated under the old requirements until their application for inclusion on the ARTG under the new requirements has been processed. At the end of the 3 year transition period biologicals that have an "effective application", submitted in the first 18 months, for inclusion on the ARTG can continue to be supplied until their application is finalised. Other applications will be considered in the normal timeframes.
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 biologicals.
Staying up-to-date on implementation of the Biologicals framework
Interested parties are encouraged to:
- complete the facilities registration update form <http://www.tga.gov.au/bt/hctfacilityreg.htm> and mail or fax to the TGA or
- register your interest to be included in future mailouts by emailing bloodandtissues@tga.gov.au.