These are explanatory notes for Therapeutic Goods Order NO. 34 - Standard for diagnostic goods of human origin.

1. The risks of infection associated with the use of human diagnostic control sera have arisen because the sera may be potentially contaminated with hepatitis virus type B and human immunodeficiency virus. Recognition should be given to the need for good laboratory practice in handling these reagents. The risks associated with the use of human sera can be minimised by the use of non-human control sera wherever possible.

HEPATITIS VIRUS TYPE B

2. The procedure used in the serological test for HBsAg to ensure compliance with the standard needs to be either a radioimmunoassay (RIA) method, a reverse passive haemagglutination (RPHA) method, an enzyme-linked immunosorbent assay (ELISA) method or a method of sufficient sensitivity to ensure compliance when tested against the reference panel of sera. If a method other than RIA, RPHA or ELISA is used it is necessary for evidence supporting the sensitivity of the proposed test method to be made available to the Department of Community Services and Health.
   It is the intention of this standard that the national control authority uses the RIA method to test for the presence of HBsAg in official samples but that the manufacturer, although obliged to carry out a test, should not be specifically restricted to using any particular test method for HBsAg. That is, the manufacturer may use the test of his choice for in-house testing to ensure that a product complies with the standard. However in the case of a dispute or for testing of official samples the RIA method will be used.
3. It is intended that positive control reagents used in the tests for hepatitis virus type B together with those products which, due to the nature of the product, could only be obtained from HBsAg positive donors or are of a quantity which precludes adequate testing, shall be exempted from the requirements to be tested for HBsAg under this Order.
4. There are two reasons why it is necessary to carry out a serological test for hepatitis virus type B on individual donor serum as well as on pooled sera, final bulk or final lot:
   1. Pooled sera may give a negative test result even though it may contain a positive donor serum because the positive donor serum has been diluted by mixing with negative donor sera beyond the sensitivity of the test method. The pool should still be regarded as infectious.
   2. Secondly, the HBsAg in a positive individual donor serum may be neutralised by antibody to HBsAg present in other donor sera included in the pool so that the HBsAg is not detectable in the test. However, the infectivity of the hepatitis virus type B may not be neutralised and the pooled sera should be regarded as hazardous.
   Testing of the final bulk or final lot provides a check against poor screening tests or the possibility of a mix-up occurring during production of several products by the same manufacturer.
5. It is recognised that it may be difficult for companies to ensure donor acceptability when they do not have access to individual donor records. In many cases only the blood collection centres would be able to determine that donors are (i) free from a history of injections with narcotics, and (ii) free from a history of infection with hepatitis virus B for a period of not less than five years or that hepatitis B surface antigens or antibody to HIV are not demonstrable in the donor's blood. Manufacturers of goods covered by this standard should therefore, where appropriate, seek the necessary assurances of donor acceptability from the source of their raw materials.
6. The national reference panel of sera for evaluating methods of detecting hepatitis B surface antigen was established with the support and assistance of the Royal College of Pathologists of Australia. The reference panel has similar characteristics to the WHO reference panel and includes sera containing antigens of both major hepatitis B subtypes encountered in Australia ("ayw" and "adw") and a range of high and low antigen titres.

Requests for the reference material, or for further information should be directed to either the -

Virology Department
Fairfield Hospital
Yarra Bend Road
FAIRFIELD VIC 3078 Telephone (03) 488 2399

or the

Virology Section
Therapeutic Goods Administration Laboratories
Private Bag 7, P.O.
PARKVILLE VIC 3052 Telephone (03) 387 4211

HUMAN IMMUNODEFICIENCY VIRUS (HIV)

7. There is a risk that diagnostic goods of human origin may be contaminated with human immunodeficiency virus (HIV), the causative agent of AIDS. Infectious HIV has been isolated from sera and other body fluids which might be used as control reagents in diagnostic work. In addition, experimental evidence indicates that samples which contain antibody to HIV may be infectious. Since sera in diagnostic goods are a potential source of AIDS infection for laboratory workers, it is now considered necessary to include testing for antibody to HIV in this Order. However, an exception is made for goods which have been processed in a manner which effectively inactivates HIV. In this case the Department of Community Services and Health may require details of the inactivation process.
8. Sensitive enzyme-linked immunosorbent assay (ELISA) tests and other tests for detecting antibody to HIV are currently available. A list of test kits approved by the Department of Community Services and Health for use in Australia is shown in the Schedule. However these tests may produce a proportion of false positive results that could result in the rejection of HIV-free sera. Therefore effective screening of sera for HIV antibody requires a two tier system where, if a manufacturer has reason to believe that the result obtained with a test is a false positive, an additional test may be performed using a different test method of greater specificity such as a Western Blot method. Persons intending to perform additional tests using other test methods should first seek the approval of the Department of Community Services and Health. Official testing, in the case of a dispute or for the testing of official samples, will be performed using an ELISA test and a Western Blot method.

LABELLING REQUIREMENTS

9. The requirement that the label attached to the goods should contain a warning that the product may be infectious has been reconsidered.
   It is now necessary to place such a warning on an information or instruction leaflet where such a leaflet is supplied with the product. In addition, the leaflet is to contain a statement that the product has been tested both for hepatitis B virus surface antigen and for antibody to HIV, and that the test results were negative.

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