Questions & answers about In Vitro Diagnostic Medical Devices (IVDs) as included in the draft Medical Devices Rule
May 2007
What is an IVD?
Under the draft Medical Devices Rule, IVDs are considered to be a subset of medical devices. For a device to be considered an IVD as referred to in this Rule, it must first fulfill the definition of a medical device. This definition includes diagnostic devices "providing information for medical purposes by means of in vitro examination of specimens derived from the human body".
If a device fulfils this definition, it then must fulfill the definition of in vitro diagnostic medical device (IVD):
- It is a reagent, calibrator, control material, kit, specimen receptacle, software, instrument, apparatus, equipment or system, whether used alone or in combination with another diagnostic product for in vitro use, and
- Is intended by the manufacturer to be used in vitro for the examination of specimens derived from the human body, solely or principally for:
- Giving information about a physiological or pathological state or a congenital abnormality
- Determining safety and compatibility with a potential recipient
- Monitoring therapeutic measures
Are in-house IVDs covered by the draft Rule?
No. It has been agreed to finalise the commercial IVD framework, before undertaking further stakeholder consultation, particularly in New Zealand, on in-house IVDs.
Will IVDs for non-therapeutic use be regulated under the joint scheme?
No. IVDs for breath/alcohol testing, substance of abuse testing and parentage or kinship testing do not fit the definition of a therapeutic good and will therefore not be regulated by the Australia New Zealand Therapeutic Products Authority (ANZTPA), unless they are supplied specifically for a therapeutic purpose.
What if people use an IVD not covered by this Rule for a therapeutic use, for instance an IVD for kinship testing used for genotyping red blood cells?
The manufacturer will indicate the intended use of the IVD through labelling etc. If a person uses an IVD for another purpose this is considered off label use and the user takes on the responsibility.
What will Variant mean for IVDs? Will it include 'pack size'?
The definition of variant for medical devices has not been amended to include IVD specific properties, and may need to be. For example, it is not intended that IVDs in different pack sizes will require a separate entry. A list of acceptable variants for IVDs will be developed. Industry’s view would be welcomed.
What are the Essential Principles that IVDs need to conform to as medical devices?
All medical devices, including IVDs, are required to comply with the Essential Principles. The Essential Principles set out requirements relating to safety and performance of medical devices.
There are three groups of Essential Principles. These are:
- the general principles that apply to all medical devices;
- particular principles about design and construction relevant to specific medical devices and IVDs; and
- particular principles that are relevant for IVDs.
The principles are aligned with the Essential Principles that have been agreed by the Global Harmonisation Task Force (GHTF), ensuring these are international requirements.
A manufacturer is responsible for ensuring that a device meets all relevant Essential Principles, when the product is used as intended.
A separate classification system exists for IVDs, as detailed in Annex 2A of the IVD Rule, and the rules and classes are aligned with the recommendations of the GHTF.
The risk classifications are:
- Class 1 IVD - Failure of such devices would result in low personal risk
- Class 2 IVD - Failure of such devices would result in low public health risk, moderate personal risk
- Class 3 IVD - Failure of such devices would result in moderate public health risk, high personal risk
- Class 4 IVD - Failure of such devices would result in high public health risk
What will happen to products where the European Union (EU) class is different to the ANZTPA class?
Manufacturers will need to classify the products according to the ANZTPA classification rules and ensure that the appropriate conformity assessment is performed.
What conformity assessment procedures will IVD manufacturers need to follow?
All IVDs must undergo a conformity assessment procedure to ensure compliance with the Essential Principles. The minimal level of rigor of this assessment ie the assessment pathway chosen, is determined by the class of the IVD which depends on level and nature of risk posed by the IVD to the patient or user. This ranges from Class 1 IVDs where the manufacturer self certifies, through to a full review of the quality management system and product design dossier review by the regulator for Class 4 IVDs.
The common aspects in most conformity assessment procedures are:
- quality management system certification;
- quality management system surveillance audits; and
- a post market monitoring system.
The following two conformity assessment procedures that apply to medical devices cannot be applied to an IVD:
- Part 4 Verification procedures, and
- Part 6 Product quality control procedures
Who needs a Conformity Assessment Certificate?
All manufacturers must apply a conformity assessment procedure to demonstrate conformance with the Essential Principles. In specified instances, a manufacturer must apply to ANZTPA to gain a Conformity Assessment Certificate (ie. Overseas certification will not be accepted). A Conformity Assessment Certificate indicates that conformity to the Essential Principles has been assessed by ANZTPA and allows the manufacturer to make a declaration of conformity.
A Conformity Assessment Certificate is required for the following IVDs:
- A manufacturer who manufactures IVDs in Australia and/or New Zealand
- IVDs manufactured outside New Zealand or Australia if they are Class 4 IVDs
- Class 2 and 3 IVDs for which the manufacturer has not undergone a suitable Conformity Assessment procedure elsewhere.
Manufacturers of Class 1 IVD's do not need an externally certified Conformity Assessment Certificate before the manufacturer can make the declaration of conformity.
Will ANZTPA accept overseas certification for IVDs?
Yes, there is agreement that IVD conformity assessment will be included in the European Community Mutual Recognition Agreement (EC MRA) and manufacturer's quality management certification in the Memorandum of Understanding (MOU) with Canada, under ANZTPA. This will mean ANZTPA can certify to European and Canadian requirements while these jurisdictions can certify to ANZTPA requirements.
Will there be provision for external assessment bodies for Australian and New Zealand manufacturers?
This issue is under consideration for medical devices and if it is a concern for the IVD industry, this should be raised in submissions for this consultation.
Are there any conditions associated with a Conformity Assessment Certificate?
Yes, when ANZTPA issues a Conformity Assessment Certificate conditions will be imposed on the certificate.
The general conditions that will apply are entry and audit powers, review, notification of substantial changes to the IVD or its manufacturing process, and fees. In addition, the Managing Director may impose special conditions on a Conformity Assessment Certificate on matters such as the quality management system or to the IVDs to which the certificate applies.
How long is a Conformity Assessment Certificate valid for?
A Conformity Assessment Certificate is valid for five years after the date of issue and at the end of this period will be re-issued for a further five years based on a satisfactory compliance and audit history.
Is a Product Licence required for an IVD?
Yes, unless exempted, IVDs may only be imported into Australia and New Zealand, exported to a third country from Australia and New Zealand, or supplied in Australia or New Zealand, by or with the consent of, the holder of a product licence.
A data base of product licences will be maintained by ANZTPA.
How do I obtain a product licence?
Unless exempted, an IVD cannot be supplied in Australia and/or New Zealand without a product licence. A sponsor must submit an application to ANZTPA accompanied by the prescribed fee. The application includes certification about a number of matters including that the device complies with the Essential Principles and has been correctly classified by the manufacturer.
In most cases, the manufacturer of a medical device must hold evidence that appropriate Conformity Assessment procedures have been followed. This evidence is then presented as part of the application process for a product licence.
What Product Licence conditions will be imposed on IVDs?
There will be some conditions applicable to all IVD product licences. They will be based around entry of the product holder’s premises and inspection powers relating to records (eg distribution and documentation supporting the Declaration of Conformity), delivery of samples, relevant information and records, and advertising material. The ANZTPA may also impose some specific conditions as part of a decision to issue a product licence.
Change of sponsor. Does the product licence holder need to make an application to change the sponsorship and will there be a fee for this?
Yes there will be a need to apply for a change in product licence holder as the new product licence holder will need to make a declaration that he/she has in place all the necessary arrangements with the manufacturer to ensure the ongoing postmarket requirements. There will be a fee for this application. There is a three month timeframe during which the new product licence holder can supply while the change application is processed.
How will IVDs be grouped under one product licence?
Products will be grouped on the basis of:
- same sponsor;
- same manufacturer;
- same class of IVD; and
- same Global Medical Device Nomenclature (GMDN) code.
Work is progressing in consultation with the GMDN Maintenance Agency on finalising the GMDN codes for IVDs. For low risk IVDs there will be limited GMDN codes for IVDs for grouping of products on a single licence whereas for Class 4 IVDs each licence will be specific for a product.
Will each class 4 IVD need a separate product licence?
Most class 4 IVDs will require a separate product licence but for Class 4 immunohaematology products there are special grouping provisions meaning one product licence will cover a group of products.
Export only IVDs will be class 1 but what GMDN code would apply for a Class 4 IVD for export only?
The GMDN that describes the device (ie the preferred term) is used. But the product would still be self certified as a class 1 IVD.
What post market surveillance, including adverse event reporting, will occur?
There will be systems, procedures and strategies in place for the reporting of problems with all medical devices, including IVDs.
A comprehensive incident monitoring programme will operate in both Australia and New Zealand. Manufacturers and product licence holders will be required to report adverse events to ANZTPA. IVD users may also submit incident reports.
Post market surveillance of IVDs by ANZTPA may include compliance testing of IVDs, and review by ANZTPA of technical files and certification.
Recalls will be classified by ANZTPA, in consultation with the sponsor where appropriate, according to a class system:
- Class I recalls occur when defects in IVDs are potentially life threatening or could cause a serious risk to health
- Class II recalls occur when defects in IVDs could cause illness or mistreatment, but are not Class 1
- Class III recalls occur when defects in IVDs may pose a significant hazard to health, but withdrawal may be initiated for other reasons
When a recall occurs the Managing Director must publish a notice setting out the particulars of the requirement.
Are the Australian and New Zealand recall procedures going to be different?
These procedures are different at the moment but there will be one uniform recall procedure under ANZTPA.
Will ANZTPA officials expect to be notified of all overseas incidents relating to IVDs?
Yes, product licence holders are to notify ANZTPA officials of serious adverse incidents involving problems with IVDs identified overseas. Guidance will be provided on postmarket reporting.
Will the sponsor’s name be required on IVD labels?
Yes. The same requirements will apply as for medical devices. There will be flexibility around the location of the sponsor’s name and address.
The addition of the sponsor’s name and address, by over-labelling, will not be considered as a manufacturing activity.
What will the fees & charges be?
An overview of the ANZTPA cost model (pdf,353kb) <http://www.anztpa.org/consult/dr-fees.pdf> is available
The model was developed in consultation with the Australian industry.
What will be the timelines for the assessment of IVDs?
As for medical devices, ANZTPA will negotiate on target timeframes with industry for the application and assessment processes.
What about timeframes for assessing Class 4 IVDs that have a short R & D phase?
It is recommended that the manufacturer contact ANZTPA during the development phase to alert ANZTPA officials on proposed forthcoming applications, in order to ensure a good quality and effective submission.
How will instruments that are part of a closed system be assessed?
While instruments are Class 1 IVDs where these are part of a closed system they will be assessed as part of the assessment of the analyte (ie a machine for testing HIV that is part of a closed system will be assessed as a class 4 IVD during the assessment of the IVD).
Are the New Zealand or Australian notifiable disease lists very different?
The New Zealand and Australian Notifiable Diseases Lists are similar. The following diseases are not common to both countries:
Australia Only – Botulism, Chlamydia infection, Donovanosis, Gonococcal infection, Haemolytic Uraemic Syndrome, Influenza other than HPAI, Pneumococcal disease (invasive), Psittacosis, Q fever, Smallpox, Syphilis, Tularaemia, Varicella.
New Zealand Only – Giardia, primary amoebic meningoencephalitis, Yersiniosis, Enterobacter salazakii disease, Rickettsial disease, Rheumatic fever, Cysticercosis, Taeniasis, Trichenosis
Does refurbishment of IVD instrumentation come under the scope of ANZTPA?
Yes, when someone other than the original manufacturer refurbishes an instrument and places it on the market in his/her own name, that person becomes the manufacturer and must comply with the requirements of this Rule.
What provision is there for access to IVDs for promotional purposes?
Exemptions exist for import for supply at trade shows or for laboratory review. Schedules 4 & 5 of the Rule detail all the various exemptions.
What is a clinical trial for IVDs?
GHTF is working on guidance for clinical evidence for IVDs. ANZTPA will adopt the GHTF guidance.
URL: http://www.anztpa.org/devices/qaivd.htm