26: Clinical Microbiology In Vitro Diagnostics in Australia

Clinical Microbiology In Vitro Diagnostics in Australia: Regulatory Requirements and Product Information

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:

  1. TGA – Therapeutic Goods Administration
  2. NPAAC – National Pathology Accreditation Advisory Council
  3. NATA – National Association of Testing Authorities
  4. RCPA QAP – Royal College of Pathologists of Australasia Quality Assurance Programs.

26.1 The Therapeutic Goods Administration

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.

26.1.1 IVD classification

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:

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

* 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. Class 4

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:

  1. transmissible agents in blood, blood components, blood products, cells, tissues or organs or any derivatives of these products of human or animal origin, in order to assess their suitability for transfusion or transplantation;
  2. a transmissible agent that causes serious disease with a high risk of propagation in the Australian population.

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. Class 3

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:

  1. testing for notifiable diseases, and/or sexually transmitted diseases, with particular emphasis on the detection of gonorrhoea (Neisseria gonorrhoeae), chlamydia (Chlamydia trachomatis), syphilis (Treponema pallidum), donovanosis (Klebsiella (Calymmatobacterium) granulomatis), genital herpes (herpes simplex virus 2), lymphogranuloma venereum (C. trachomatis serovars L-1, L-2, L-3), genital warts (human papillomavirus) and trichomoniasis (Trichomonas vaginalis), are Class 3 IVDs (excluded are tests for HIV, HCV, and hepatitis B virus regarded as serious diseases and graded as Class 4);
  2. detection of an infectious agent with a risk of limited propagation in cerebrospinal fluid or blood;
  3. detection of an infectious agent where an erroneous result is likely to cause death or severe disability to an individual or fetus being tested (e.g., MRSA);
  4. pre-natal screening of women in order to determine their immune status towards transmissible agents;
  5. detection of biological markers to assess the immunological compatibility of blood, blood components, tissues or organs for transfusion or transplantation, if not classified higher, like transfusion antibodies not included in Class 4 (e.g. Cw or V from the Rhesus system, Cellano (k) from the Kell blood group system, any markers from MNS and Cartwright blood group systems);
  6. determining infectious disease or immune status, when a therapy decision is to immediately follow diagnosis and when the device is not used for mere monitoring purposes (Class 2 IVD);
  7. selecting patients for (i) selective therapy and management, (ii) disease staging, (iii) diagnosis of cancer;
  8. human genetic testing – all devices are Class 3 IVDs (Philadelphia chromosome, Huntington’s disease or cystic fibrosis IVDs), as are IVDs screening for congenital disorders (pre- and post-natal tests for trisomy, Klinefelter’s syndrome, etc.) and any kits or individually supplied reagents intended to be used for the in situ hybridization of targeted gene polymorphisms;
  9. monitoring levels of medicines, substances or biological components;
  10. managing patients suffering from a life-threatening infectious disease;
  11. self-testing IVDs, where the diagnosis has to be validated by a health professional and safe treatment supervised (blood glucose self-monitoring tests). Class 2

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:

  1. monitoring a condition (e.g., total PSA detection) or initial screening for a condition (e.g., fecal occult blood screening test) where the result requires further investigation prior therapy;
  2. self-testing devices not used to diagnose serious ailments or used to test preliminary conditions (i.e., pregnancy kits or urine self-test strips);
  3. nonassay-specific quality control material (controls, calibrators, and standards not assigned for use with a specific assay);
  4. detecting infectious agents that are not easily propagated in a population;
  5. any other medical device not specified elsewhere in the legislation;
  6. staining solutions intended for a specific diagnostic purpose.

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

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Dec 10, 2017 | Posted by in MICROBIOLOGY | Comments Off on 26: Clinical Microbiology In Vitro Diagnostics in Australia

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