On 1 July this year, TGA introduced a new scheme for the regulation of in vitro diagnostic products (IVDs) in Australia, based on the current system for regulation of medical devices.
IVDs are medical devices intended for the examination of specimens from the human body for the purposes of:
- giving information about a physiological state;
- determining compatibility for a potential recipient; or
- monitoring therapeutic measures.
This covers a wide range of devices, but includes, for example, analytical reagents, instruments, test kits, control samples and sample collection devices such as blood collection tubes. It also includes tests developed by analytical laboratories for in-house measurement of samples.
The introduction of a new regulatory regime for IVDs promises to be a challenge for this previously mainly unregulated sector.
Prior to 1 July, TGA did not regulate most of the above devices. Pre-market assessment and registration was limited to tests for HIV and HCV, while some home-use tests (or those that used human materials) were subject to listing, with no pre-market review.
With few exceptions – and after a four-year transition period (ending 30 June 2014) –IVDs must meet TGA approval and be included in the ARTG prior to being supplied in Australia.
Risk and regulation
The above changes have occurred due to amendment of the Medical Devices Regulations, and covers IVDs as a subset of medical devices. The level of regulation uses a risk-based approach, similar to that in place since 2007 for other medical devices.
The level of TGA regulation and review will depend on an IVD’s risk class. These are assigned by the manufacturer and are based on the IVD’s intended use and the risk posed through its use.
Like medical devices, there are four risk classes (below). Risk is determined by a combination of the public health risk (e.g. from blood or other tissues) and the personal risk (i.e. the risk to the patient from an incorrect result):
Class 1 – No public health risk or low personal risk
- Reagents used for IVD procedures
- Specimen receptacle (e.g. blood collection tube)§ Instruments§ Culture media
- IVDs for export only
Class 2 – Low public health risk or moderate personal risk
- Default class for devices that do not fall into another class
- Non-assay specific QC material
- Pregnancy self-tests
Class 3 – Moderate public health risk or high personal risk
- Human genetic testing§ Tests for disease staging (e.g. HIV viral load)
- Foetal testing for congenital disease
- IVDs for self-testing (e.g. glucose monitoring)
Class 4 – High public health risk
- IVDs used to test tissues for transplantation
- Blood donation testing (including blood grouping)§ HIV, HCV, SARS tests
If a number of IVDs and/or medical devices are included as part of a system or pack, the classification for the whole is taken to be the highest classification of an individual IVD in the pack.
The level of assessment required for approval depends on the risk class and is equivalent to that imposed for Medical Devices. For all IVD classes, a Declaration of Conformity must be completed and signed by the manufacturer, and appropriate post-marketing and adverse event reporting systems must be in place.
The additional documentation required varies. For example, Class 1 IVDs require evidence of an appropriate quality system and holding a technical file, whereas Class 4 requires the provision of details of the quality system, examination of the design dossier, risk analysis and compliance with essential principles. (Detailed information on the classification and data requirements is available at the TGA website.)
Limiting the burden
The regulation of in-house IVDs was recognised as a particular challenge. These are defined as IVDs developed from first principles (from a published or other source) that include modifications from the manufacturer’s intended purpose not supplied externally to the laboratory or network.
In-house IVDs in Classes 1-3 will require ISO-15189-NATA certification and must comply with the NPAAC validation standard. They will be notified to the TGA and entered on a special in-house database, rather than the ARTG. Class 4 in-house IVDs will be regulated in the same way as other Class 4 IVDs. It is hoped this approach will limit the regulatory burden for laboratories using such tests.
Note that the definition of an in-house test includes tests used for purposes other than the manufacturer’s original intended purpose. Therefore, for example, if a laboratory has purchased a test kit but then uses it for anything other than its original intended purpose, it becomes an in-house test and will likely require inclusion in the TGA database.
Multiples cut costs
Similar to other medical devices, IVDs may be grouped into a single application if they’re considered the ‘same kind of medical device’. These are IVDs that have the same manufacturer, sponsor, IVD classification and GMDN code. This may allow simultaneous approval of a number of products, offering significant time and fee savings.
Fees for inclusion of IVDs follow the same approach as for other medical devices, with costs increasing depending on the class of IVD and the level of assessment required. This can vary from an application fee of $790 for Class 1 devices up to tens of thousands of dollars where full quality system audits or design examinations are required.
The fees can, however, be reduced significantly where multiple applications share common data or after consideration of public health interests and commercial viability.
To encourage sponsors to act early (and recalling the rush of applications prior to the deadline for the current medical device scheme in 2007), TGA will waive annual charges for any IVD transitioned to the new system prior to July 2014.
As for other medical devices, procedures allow supply of unapproved IVDs, via the Special Access Scheme, or in cases of national emergency.
While the full impact of these changes on industry are unclear, IVD Australia has indicated that it is likely that the changes in 2014 will result in the removal from the market of some low-volume, high-risk tests, and that many newer tests, such as the pharmacogenomic tests currently under development, may never be marketed in Australia. This increase in regulatory burden may result in a significant reduction in the use of in-house tests.