CHAPTER 26 Carola Venturini1, Vitali Sintchenko1,2,3, and Jonathan R. Iredell1,2,3 1 Westmead Millennium Institute, Westmead, NSW, Australia 2 Westmead Hospital, Westmead, NSW, Australia 3 University of Sydney, Sydney, NSW, Australia Australia uses the international definition of in vitro diagnostic devices (IVDs) (Directive 98/79/EC) [1] and Australian diagnostic microbiology laboratories use a mix of imported and in-house IVDs. While IVDs licensed overseas often have the advantage of prior rigorous testing (e.g., in North American and/or European jurisdictions) and published track records of clinical performance, regional variation and minor epidemiological differences can occasionally prove problematic. Australia manufactures relatively few IVDs and the majority of IVDs in use are produced overseas. However, in-house devices, i.e., devices “developed or modified by providers for use in their own laboratories”, are common. Several organizations govern the development and implementation of diagnostic services in Australia, including imported and in-house IVDs: The Therapeutic Goods Administration is part of the Australian Government Department of Health, and oversees the regulatory control process on all therapeutic goods, including any medical devices manufactured, sold, and used in Australia [2]. The TGA authority over medical devices derives from the “Therapeutic Goods Act 1989”. With Food Standards Australia and New Zealand, providing for oversight of foodstuffs [3], the TGA is the Australian counterpart of the American Food and Drug Administration. The main roles of the TGA are to provide standards and conformity assessment procedures, post-marketing activities, compliance testing and licensing, and to allow for adverse event reporting and recalls, as well as provision of access to unregistered IVDs in cases of special needs. The TGA specifies both performance and safety guidelines. Foreign IVD manufacturers must have an Australian sponsor sharing legal responsibilities and participating in registration of the device. Prior to market release, all IVDs must be registered on the Australian Register of Therapeutic Goods (ARTG) under standard Global Medical Device Nomenclature (GMDN). The TGA recovers operational costs through charges and fees to manufacturers and sponsors, as well as penalties for a range of offences from illegal importation, exportation, manufacture or supply of medical devices, to making false declarations (Therapeutic Goods Act 1989). The TGA defines IVDs as “pathology tests and related instrumentation used to carry out testing on human samples, where the results are intended to assist in clinical diagnosis or in making decisions concerning clinical management”. All IVDs for use in diagnostic laboratories, at the point of care, and in the home come under TGA jurisdiction. The TGA’s regulation of IVDs is separate from that of other medical devices and carries its own specific classification system originally in line with the Global Harmonization Task Force (GHTF) (now replaced by the International Medical device Regulation Forum – IMDRF) [4]. IVDs classified and regulated by the TGA legislation must be explicitly intended for therapeutic use. Products without therapeutic purpose (e.g., tests for parentage and kinship testing; alcohol and illicit drugs tests) and those used solely in veterinary medicine are exempt from TGA regulation. As medical devices, all IVDs must comply for their entire lifespan with a series of Essential Principles set out by the TGA for quality, safety and performance [5], and the manufacturer is responsible for ensuring compliance and must provide evidence of performance and safety of the product to the TGA. Prior to 2010, IVD regulation was limited with no form of pre-market examination. Since 2010, however, efforts have been in place to update the regulatory framework in order to standardize Australian legislation with international guidelines [6]. All established and yet-to-be developed IVDs, both commercial and in-house, from tests for serious infectious diseases, tests for screening blood, tissues and organs, through to home pregnancy tests and glucose monitors, are expected to be regulated under this new framework from July 2014. The TGA’s current legislative framework ensures both pre-market assessment and post-market control for all IVDs, with level of scrutiny based on the risk associated with each specific device. Both commercial and in-house IVDs are classified by the TGA based on the risk they pose and on their intended use [7]. Classification rules generally aligned with the GHTF guidelines and IVDs fall into four categories as follows: * Any test where an erroneous result could lead to death or major injury, e.g., detection of malaria parasites in blood, cryptococcal antigen in CSF, etc. The legislation requires each IVD to be classified separately when used in conjunction with other IVDs. In systems and procedure packs containing one or more IVDs along with non-IVD devices (calibration, quality control materials, etc.), the IVD with the highest class will determine the class of the overall pack. IVDs used for the detection of transmissible agents that present a high threat to the health of the Australian population belong to Class 4. Specifically, Class 4 includes IVDs used to detect: Front-line or screening assays, confirmatory and supplemental assays, IVDs that detect structural components or surrogate markers of transmissible agents that cause serious disease, belong to this highest risk class. Intended use is also significant. For example, a syphilis assay will be a Class 4 IVD if used to screen blood and tissue donations, but Class 3 if used for diagnostic purposes only. Tests to establish the safety of blood and blood components for use, such as exotoxin activity assays (pyrogenicity tests) when specifically used to detect bacterial contamination of blood, and IVDs used to diagnose clinical infections that cause serious disease with a high risk of transmission from person to person in the Australian population, are Class 4 IVDs, including tests for detection of severe acute respiratory syndrome-associated coronavirus (SARS-CoV), highly virulent pandemic influenza, viral hemorrhagic fevers such as Ebola virus, all assays to diagnose HIV-1 and 2 infection, and hepatitis C and B viruses. These IVDs are designed to identify a high individual risk, being tests aimed to provide a direct diagnosis, whereby an erroneous result would lead to an immediate threat to life, such as: Class 2 comprises devices that pose a low public health risk or moderate personal risk. The results from IVDs included in Class 2 are not meant to be used alone for a definitive correct diagnosis, and the likelihood that an erroneous test result will have a significant negative impact on patient outcome is negligible. Class 2 IVDs are those used for/as: The manufacturer’s specified intended use for a reagent, stain, or kit becomes a very important discriminating factor in classification of low-risk IVDs. Although general reagents not manufactured or supplied specifically for in vitro
Clinical Microbiology In Vitro Diagnostics in Australia: Regulatory Requirements and Product Information
26.1 The Therapeutic Goods Administration
26.1.1 IVD classification
Classification
Level of risk
Example
Class 1 IVD
No public health risk or low personal risk
Gram’s staining solutions; general culture media
Class 2 IVD
Low public health risk or moderate personal risk
Viral tissue culture system; specific DFA assays
Class 3 IVD
Moderate public health risk or high personal risk
HIV genotyping; blood/CSF* testing
Class 4 IVD
High public health risk
blood supply screening; HIV diagnosis
26.1.1.1 Class 4
26.1.1.2 Class 3
26.1.1.3 Class 2
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