Draft guidelines: In vitro diagnostic goods for home-use
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In July 2003, the TGA consulted on a guidelines document (below) developed by the Office of Devices, Blood and Tissues for sponsors of home-use in vitro diagnostic devices (IVDs).
The consultation period closed on 1 August 2003. Stakeholders will be advised when the new document is implemented.
In vitro diagnostic goods for home-use - draft guidelines for sponsors (June 2003)
Australia's new regulatory system for medical devices was introduced in October 2002. Importantly, the new regulatory framework for medical devices excludes in vitro diagnostic devices (IVDs), devices of human origin, and devices containing viable cells or tissue of animal origin. Although these products fit the definition of a medical device, they have been excluded because the Australian Government is developing new regulatory frameworks for them. In the interim period these products will be regulated as per the previous system, as 'other therapeutic goods'.
IVDs continue to be regulated as either 'registrable', 'listable' or 'exempt' goods, with the same Therapeutic Goods Administration (TGA) pre-market evaluation and manufacturer licensing requirements and procedures as generally applied previously (Sections 25, 26, 35 and 36 of the Therapeutic Goods Act 1989 (the Act)).
The regulation of IVDs by the TGA is tabulated below.
|ARTG status||IVD 'type'||Legal basis for regulation|
Diagnostic goods for in vitro use in the diagnosis of:
|Therapeutic Goods Regulations 1990 |
Schedule 3 Part 2 Item 7
Diagnostic goods for in vitro use:
|Therapeutic Goods Regulations 1990 |
Schedule 4 Part 1 Item 2
Schedule 5 Item 7(b)
|Exempt||All other diagnostic goods for in vitro use||Therapeutic Goods Regulations 1990 |
Schedule 5 Item 7(b)
The purpose of this guideline is to:
- outline the approach of the TGA to the regulation of home-use IVDs; and
- identify key issues to be considered by manufacturers and sponsors of home-use IVDs, including the data requirements of the TGA.
The guideline is intended for use as a supplement to information about listable IVDs contained in Chapter 3.21 of the Australian Medical Device Requirements - Version 4, May 1998 (DR-4).
2. Acronyms and abbreviations
|ARTG||Australian Register of Therapeutic Goods|
|DR-4||Australian Medical Device Requirements - Version 4, May 1998|
|IVDs||in vitro diagnostic devices|
|TGA||Therapeutic Goods Administration|
|the Act||Therapeutic Goods Act 1989|
3. Home-use IVDs
Traditionally, most IVDs available in Australia have been designed exclusively for use in a health care setting or by a health care professional, and fall within the exempt category of IVD.
Home-use IVDs are those intended for supply to a person for that person to either:
- diagnose or monitor a medical condition in that person or the immediate family of that person - the person collects a sample, conducts the test and then interprets the results of the test, with no involvement of a health care professional; or
- use in the collection of a sample that is forwarded and tested by a laboratory/health care professional.
In the past, the most commonly marketed home-use IVDs have been those used to either diagnose non-serious conditions (eg pregnancy, ovulation status) or monitor conditions after diagnosis (eg diabetes or anticoagulant monitoring). In the latter case, the interpretation of results by the patient has been underpinned by support structures such as educational material and nurse/clinic support and the home monitoring is part of a continuum of treatment.
However, the TGA has recently received applications from sponsors wishing to market a variety of home-use IVDs for diagnosis of a wide range of serious medical conditions. This includes tests for infectious diseases and conditions that are imminently life-threatening. The scope of applications received by the TGA includes antibodies to tuberculosis, cancer markers such as prostate specific antigen, cardiac enzymes such as myoglobin, and antibodies to Hepatitis B surface antigen. The use of such tests in a non-professional setting poses a range of individual and public health issues that should be addressed by laboratory and clinical data to establish the overall safety of the test.
4. Safety issues arising from the marketing of home-use IVDs
The home-use environment differs from the clinical laboratory in four important ways that may impact on the potential risks of an IVD:
- a consumer may lack the necessary training to interpret a test result in the context of other relevant clinical information, such as, pertinent personal or family medical history, symptoms and physical examination;
- the consumer may not understand the test and/or not interpret directions for use carefully and, thus, conduct the test incorrectly;
- the consumer may or may not carry out necessary follow-up actions on the basis of a false result; and
- the person collecting a sample and sending it to a clinical laboratory may lack the technical training to ensure that the specimen that arrives at the clinical laboratory in the same condition as when it was collected.
As home-use IVDs function in essentially the same manner as professional use/laboratory IVDs, their performance characteristics can be defined in terms of traditional performance parameters such as sensitivity, specificity, accuracy, and reproducibility of test results.
However, the performance of the device in the hands of skilled users may not reflect the device's performance in the hands of consumers. Consequently, attention must be given to the following criteria for safe use of an IVD in the home:
- for a given intended use, the analytical performance of the home-use IVD (ie its ability to detect and/or measure a particular analyte) should be comparable to the performance of IVDs intended for the same purpose that are used by professionals in clinical settings;
- the device's performance should not be appreciably affected by anticipated variation in user technique;
- home-use IVDs should include a simple method by which the user can reasonably verify that the product's performance meets its design specifications at the time of use;
- the home-use IVD should not pose any undue infective risk to the user or wider community; and
- home-use IVDs should include sufficient information for the user to interpret the result properly and to take appropriate follow up action.
5. TGA approach
When determining whether a listable product can be entered into the Australian Register of Therapeutic Goods (ARTG), the TGA is required to determine whether, among other criteria:
- the goods are safe for the purposes for which they are to be used;
- the presentation of the goods is acceptable; and
- the goods comply with prescribed quality and safety criteria.
It is the view of the TGA that performance characteristics, usability and labelling are all critical to the safe use of an IVD intended for home-use. The assessment of safety of an IVD intended for home-use must include consideration of the consequences if the goods do not perform adequately in home-use, particularly where the goods are to be used for the purpose of detecting serious medical conditions. A false positive result in the home use of the goods may lead a person to believe that they have a serious or fatal illness, while a false negative result in the home use of such goods may result in a person not seeking or delaying seeking appropriate treatment of a serious or fatal illness. Goods for which home use might result in unacceptable levels of false positive or false negative results can be regarded as not safe for the purpose for which they are to be used.
The Act allows the TGA to seek information about the goods under section 31 before reaching a decision about whether to list the goods or not, including information about the safety of the goods for the purposes for which they are to be used. The TGA will, therefore, assess each application for listing of home-use IVDs on a case-by-case basis, taking into account the clinical context in which a test is to be used.
Where the test is proposed for use in the diagnosis or monitoring of a serious or potentially life-threatening condition without any prior and ongoing medical oversight, the TGA will conduct a safety evaluation of the home-use IVD. Under such circumstances the sponsor will be required to submit data outlined below to demonstrate compliance with the criteria for safe use of an IVD in the home as stated in section 4 of this guideline.
Note: These data are meant to specifically address the home-use safety aspects of the IVD and are required in addition to standard requirements for any listable IVD (eg TGO 34 for an IVD incorporating material of human origin), as per Chapter 3.21 of DR-4.
5.1 Data requirements for home-use IVDs
- description of the test
- A detailed description of the principles of the assay and details of all reagents used in the procedure should be provided.
- This should include either details of the quality control step by which a consumer can establish the IVD has performed satisfactorily at the time of use or, if such a step has been omitted, justification of its omission on scientific grounds.
- If the IVD contains an antigen, details of the method of fixation and comments on the viability of the pathogen following fixation should be included. Information about source of material of biological origin should be given, including the nature of veterinary controls for animals used as a source of sera or antibodies.
- laboratory studies
- Laboratory data should address the following issues:
- analytical performance characteristics of the device (ie sensitivity, specificity, accuracy, and reproducibility) under controlled conditions.
- This should be done using standard laboratory measurements and appropriate, validated reference tests.
- The data should be presented as a formal, signed study report, documenting the methods, results and conclusion of the study. The methodology section should include the name, the performance characteristics and details of the validation of the reference test, and the quality control procedures employed during the study.
- infectivity risks
- Where applicable, data should be submitted to address infection risk.
- Any submission for a home-use IVD that incorporates material of human origin must include data to demonstrate that where human serum or plasma are used as controls, these have been tested for antibodies to HIV I and II, HTLV, HCV, HBsAg and syphilis and found negative.
- Any claims about the viability of pathogens used as antigens should also be supported by data.
- Real time stability data on testing carried out at various time intervals at the recommended storage temperature of at least three production batches in support of the proposed shelf life should be provided. If more than one assay result is available for any particular time interval, all results should be quoted, rather than, or in addition to, an average figure.
- If real time stability data are not available, a limited shelf life may be considered (3-6 months).
- clinical study(s) of the performance of the device when used by consumers (consumer field study), assisted only by instructions provided in the labelling of the device
- The primary goal of the consumer field study should be to establish comparable levels of test performance for a particular home-use IVD when comparison-tested by both intended users and trained laboratory personnel.
- The data should be presented as a formal, signed study report, documenting the design, ethical conduct, results and conclusion of the study.
- It is recommended that split clinical samples be tested by both lay users and trained laboratory personnel with both groups using the home-use IVD. Such testing will simultaneously validate the technical performance characteristics of the device and the device's labelling based on user experience.
- To avoid potential problems of bias during data collection and evaluation of the consumer field study, a double blind design should be used - ie study personnel and consumer are both blinded to the true status of the sample being tested. However, in studies where such a design is impossible or impractical, a single blind approach and other measures to reduce potential bias may be acceptable. The manufacturer should be careful to select the appropriate type of study to ensure that the study will provide appropriate information.
- In order to assess the ability of lay users to properly store the IVD and perform and interpret test results, it is recommended that the study include simple questionnaires to determine if consumers can read and understand the labelling. For example, a questionnaire could be used to determine if the user understands the purpose of the test, the conditions for its storage and use, the test's limitations, the meaning of the results and appropriate follow-up. Samples of the questionnaires should be included in the study report, as well as a tabulation of study participants' responses to each question.
- Consumers selected for study should be representative of target users for which the test is intended. A representative study population may require the selection of individuals of varied background, education levels, and age groups. Consequently, subjects should be selected for testing based on carefully developed selection criteria. The selection criteria should be outlined in the study report and should be justified.
- The number of subjects selected for testing should be sufficient to substantiate that all targeted lay user populations can perform and interpret the test. It is recommended that the number of subjects selected for study be based on a statistically valid sampling of relevant lay users and should take into account appropriate demographic factors.
- Test results should be analysed using appropriate statistical methods to demonstrate correlation of results obtained by the lay users and trained technologists performing the test.
- labelling of home-use IVDs
- Copies of the outer packaging, container label and package insert should be supplied.
- As a general guide, the outer packaging and container label of a home-use IVD should include:
- the device name;
- the name and quantities (in Standard International Units) of all reagents;
- infectivity warnings appropriate to the nature of the IVD;
- the name and address of the sponsor of the product;
- the batch or lot number;
- the AUST L number; and
- the expiry date and recommended storage conditions.
- The package insert should also include the following additional information:
- 'directions for use' that are in simple English, concise, easy to understand, make liberal use of illustrations and drawings, use bold print or other methods to highlight warnings and precautions. In particular, it should include sufficient information to ensure the safe disposal of the product, especially for whole blood-based tests; and
- separate information, also in Plain English, relating to interpretation of results that explains the meaning of false positive and negative results and the implications of false results and, in particular, what appropriate follow-up action should be taken by the consumer (for example, in relation to persisting symptoms and signs).
6. Further information
Further information can be obtained from the Medical Devices Information Unit of the Office of Devices, Blood and Tissues:
Telephone: 1800 141 144
Facsimile: 02 6232 8299
Mail: PO Box 100, Woden ACT 2606