Laboratorydeveloped tests and medical device regulations

Genetic testing is characterized by a high degree of dependence on laboratory-developed tests (LDTs). In the European Union, Sweden and Australia, LDTs are included in the device regulations (although there are exemptions in the EU system for laboratories based within health institutions). In Canada, device regulators have sought legal opinion on whether they can regulate LDTs and have received a succession of conflicting opinions. Recently, they have stated that the development and use of an LDT within a health care facility does not constitute a 'sale' as defined in the Canadian Food and Drugs Act since legal ownership of the LDT does not change. Should the health care facility share their proprietary LDT with other health care facilities so that they may test samples, however, it would constitute a 'sale' and the LDT would be subject to the applicable provisions of the Act and Medical Devices Regulations (Hogarth, 2007).

The FDA has vacillated on the issue of whether they have the authority to regulate in-house tests but, in the last 2 years, the agency has gradually begun to intervene on a case-by-case basis. This piecemeal approach has now culminated in a draft FDA guidance in which the agency asserts it has authority to regulate in-house tests as medical devices and indicates it is now intending to exercise that authority over a class of complex tests that require interpretative algorithms to generate results (referred to as IVDMIAs—in vitro diagnostic multivariate assays) (FDA, 2006a).

While Europe treats commercial LDTs as devices subject to the IVD Directive, it is not clear that this applies to LDTs performed by laboratories outside Europe. For instance, the US companies InterGenetics and Myriad have both made their tests available through third parties in the UK; others, such as Genomic Health, are following suit. These UK third parties collect the samples and return the results to consumers, but the test is performed by the company in the USA in their own reference laboratory. The regulatory status of such tests is currently unclear. Were such US companies to be exempted from the Directive, it may place European LDT companies at a commercial disadvantage. For instance, the Dutch company Agendia, whose MammaPrint test is the main competitor of Genomic Health's Oncotype Dx, not only needed a CE mark for their test in Europe, but had to gain FDA approval to market their test in the USA. (A CE mark—'Conformité Européene'—denotes compliance with relevant European regulatory directives.)

The provision of information is another area where there is a clear difference between device regulation and the regulation of LDTs. Even where they have been deemed medical devices, there is currently no regulatory equivalent of a label for LDTs. Although laboratory regulation covers interpretation of test results and communication of results to doctors/patients, this is at the post-test stage. These regulatory regimes do not address the pre-test stage, where doctors and their patients are deciding whether to use a test. Furthermore, there are no statutory regulations on what types of data should be in a test results report (although this is addressed in professional guidelines such as those produced by the College of American Pathologists, 2007).

This lack of control over the provision of information about LDTs becomes particularly problematic when such tests are sold direct-to-consumer (DTC). IVD regulations do acknowledge that DTC testing kits pose specific risks that merit greater regulatory scrutiny. For instance, in Europe, self-testing kits (e.g. glucose meters) are reviewed by a notified body to ensure they can be understood and used easily by the lay public. The Directive states that:

the results need to be expressed and presented in a way that is readily understood by a lay person; information needs to be provided with advice to the user on action to be taken (in case of positive, negative or indeterminate result) and on the possibility of a false positive or false negative result (European Commission, 1998).

This higher level of regulatory scrutiny does not apply to a DTC testing service, despite the fact that the consumer is no better prepared to understand the test results than if they had purchased the test as a kit. This is another example of the uneven playing field between kits and LDTs.

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