Singapore, May 13, 2010: The long awaited IVD Regulations were finally passed into legislation on February 25, 2010 with their approval by the Executive Council. The Regulations consist of necessary amendments to the Medical Device regulations and as expected have a commencement date of July 1, 2010.

The IVD Regulatory Framework, as it has become known, was first conceived in 2002 when the Therapeutic Goods Administration (TGA) of Australia, in consultation with industry, proposed a new regulatory framework that was “harmonized with world best practice” to complement the revised medical device framework that was to be introduced in October 2002. In October 2003, following consultation with stakeholders, the Australian Health Minister’s Conference (AHMC) agreed in principle to the introduction of the proposed framework, including the regulation of laboratory developed (also known as “in-house”) assays. In April 2004, AHMC endorsed the Regulatory Impact Statement, and the TGA commenced drafting of the necessary changes to the medical device regulations.

The changes were however significantly delayed by the failed implementation of the combined Australian and New Zealand Therapeutic Products Authority (ANZTPA), and serious negotiation did not recommence until the beginning of 2009. Since that time, with the formation of IVD Australia in July 2009, a great deal of discussion has taken place on the details of the proposed regulations.

The new regulations provide the mechanism for the regulation of all in vitro diagnostic devices supplied in Australia. Until now only a very limited range of IVDs have required pre-market regulatory approval and inclusion on the the Australian Register of Therapeutic Goods (ARTG). IVDs intended to screen the Blood supply for HIV or HCV have to be registered, whilst those sold over the counter to consumers (home use IVDs) or on the Pharmaceutical Benefits schedule together with those that contain material of human origin have had to be listed. Under the new regulatory scheme all IVDs will be required to be included on the ARTG before they can be supplied in Australia. Products that are on the market in Australia on or before June 30, 2010 will have a four year transition period to enable sponsors and manufacturers to make application for their inclusion.

The regulatory framework is based on the Global Harmonization Task Force (GHTF) model and is quite different from the current European and US systems. IVDs will be classified into four classes based on assessed personal and public health risk, with the highest risk products being included in Class 4 and lower risk products in Classes 3, 2 and 1. The Australian model is unique in its provision for products to be grouped with the lowest class (Class 1) having only 11 possible groups. Products will be entered onto the ARTG using Global Medical Device Nomenclature (GMDN) codes which have been created by the GMDN Maintenance Agency with the assistance of the TGA and Australian industry. This has resulted in the creation of over 12,000 new preferred terms and 250 new collective terms to describe IVD products.

Sponsors will be required to have an ARTG inclusion for each “kind of IVD Device” based on four criteria; same sponsor; same legal manufacturer, same class and same GMDN Code. The classification rules, which will be subject to periodic review, are to be incorporated within the revised regulations. All manufacturers must make a declaration of Conformity to the Australian Essential Principles (EP’s), which will be required to be supplied with applications for higher class (3 and 4) inclusions.

Class 1 encompasses products with low personal risk and no public health risk such as specimen receptacles, microbiological culture media, general purpose reagents such as histological stains as well as instruments that can be used with reagents from a number of manufacturers, such as plate processors, washers and the like. Class 1 will also include IVDs manufactured in Australia that are intended for export only. These products will be able to be self declared as conforming to the EP’s and included on the ARTG with the payment of an application fee only.

Products that fall into Class 2 are those where there is moderate personal risk or low public health risk and will include many over-the-counter assays such as home pregnancy test kits and those assays where the result is used as an aid in the diagnosis of a disease or condition and is used in conjunction with other assays or examinations. Class 2 will in general be the default classification.

Class 3 will capture many infectious disease products including those that are on the National Notifiable Diseases Surveillance Scheme (NNDSS), some cardiac and cancer markers, some inmmunohematology reagents, and those assays where the result is the sole determinant for diagnosis of a disease or where an erroneous result would expose the patient to an immediate life threatening situation. Sponsors will be required to submit a Manufacturer’s Declaration of Conformity at the time of application and the TGA will conduct a Technical File Review (TFR) on inclusions incorporating product that constitute NNDSS laboratory evidence of a transmissible disease or where there is insufficient Manufacturer’s Evidence. Whilst the TGA may conduct more than one TFR per application for inclusion, they have agreed that only one fee (of $5290) will be charged regardless of the number of TFRs undertaken.

IVDs that will be classified as Class 4 are high public risk assays including those used for screening the blood supply for transmissible agents such as HCV, HIV and malaria as well as immunohematology reagents for ABO, Rhesus, Duffy, Kell and Kidd blood groups. These inclusions will require a TGA Conformity Assessment Certificate (CAC) to be issued and in many cases performance testing to Australian conditions will be required. A TGA CAC will also continue to be required for Australian Manufacturers of Class 2 or 3 IVDs.

The assignment of products into a particular risk Class will be based on a series of classification rules which will be written into the Regulations. Classification will rely heavily on the “manufacturer’s intended purpose” as set out in the product’s documentation, including the Instructions for Use (IFU), product labels and in other material such as advertising and promotional brochures. A number of products still remain exempt from inclusion; these will include products used solely for workplace or home drugs of abuse and alcohol testing, genetic tests for the determination of parentage or relationship as well as IVDs used exclusively for veterinary purposes. These products are not considered to be “therapeutic goods” and will not be regulated by the TGA. However, drugs of abuse assays which have a therapeutic intended use will not be exempt and will be subject to regulation by the TGA. Finally, the supply of home use tests for notifiable infectious diseases, cancer makers, myocardial infarction or genetic disorders will not be permitted under the new regulations.

An important addition to the new Framework is that the regulations will also capture “in-house” or “laboratory developed” tests although these will not, with the exception of Class 4 assays, be regulated to the same degree as commercial assays. Laboratories that develop their own assays for use within their laboratory group must comply with a recently introduced accreditation standard but will only be required to supply the TGA with a list of assays for incorporation on a register. There will be no regulatory assessment of these products even at the Class 3 level.

IVD Australia remains concerned at a number of aspects of the new Framework however. Firstly, there will be a dramatic increase in the cost of regulation. The TGA’s own estimate is that the cost over the first five years of the new regulations will be in the order of $16 million dollars. IVD Australia believes however that the direct cost to sponsors and manufacturers will exceed A$20 million. In addition most Australian sponsors and manufacturers will require additional staff and expertise to enable them to collect the documentation and make the necessary applications.

Many of the documents required by the TGA will exist in electronic form only and may be scattered across a series of manufacturing sites. Bringing these documents together to submit to the TGA within the specified 20 business days for a TFR may prove to be a significant logistical exercise, especially for distributors who often handle products from multiple manufacturers. This indirect overhead will add enormously to the costs of IVD companies in Australia; costs that will need to be recovered from pathology sector customers, and ultimately from the Australian community.

IVD Australia is also very concerned that the cost of regulation, both direct and indirect, will cause sponsors to reassess the importation of marginal products. In the case of some assays the direct cost is likely to exceed A$40,000 to include a single product on the ARTG and hence whilst existing products may continue to be supplied during the transition period, IVD Australia is convinced there will a significant number of products that will not be transitioned by June 2014, even allowing for the application of the TGA Low Volume/ Low Value business rules.

As with the revised Medical Device regulations, the new IVD Framework proposes an increased emphasis on post-market surveillance activities by the TGA. However this is unlikely to commence in a major way until the end of the transition period IVD Australia will be developing hands-on training for members in conjunction with the TGA to ensure that they are up-to-date with the new Regulations and with the TGA’s electronic application (eBS) system. However, it will be incumbent upon sponsors to ensure that their manufactures are aware of the Australian IVD Regulations, and their forthcoming obligations under the Therapeutic Goods Act.