Letter to In Vitro Diagnostic Reagent Manufacturers (12/6/85)

December 6, 1985

Food and Drug Administration
8757 Georgia Avenue 
Silver Spring MD 20910


TO:  In Vitro Diagnostic Reagent Manufacturers

Dear Sir or Madam:

This letter will provide guidance to manufacturers on the
labeling of human blood derived in-vitro diagnostic devices
(e.g., human serum reagents or quality control. materials) in
regard to labeling for HTLV-III/LAV antibody testing.

There have been no known reported cases of HTLV-III/LAV
transmission by contact with in-vitro diagnostic products. 
However, the possibility of transmitting HTLV-III/LAV to
laboratory employees and others who come in contact with these
materials cannot be excluded.  In order to minimize the risk of
transmission, the Center for Devices and Radiological Health has
formulated the following labeling guidelines for these products.

In-vitro diagnostic devices in which human blood or serum
components are used and which are subject to the requirements of
21 CFR 809.10 must carry as part of the labeling, information
describing the status of the blood or serum used in the reagents,
kits, devices.  In terms of the potential biohazard risk to
HTLV-III/LAV , we suggest additional labeling statements for
immediate containers, packages, and package inserts include the
following:

     1)   On the immediate container, packages, and package
          insert:

          Each donor unit used in the preparation of this
          material was tested by an FDA approved method for the
          presence of the antibody to HTLV-III/LAV as well as
          for hepatitis B surface antigen and found to be
          negative (were not repeatedly reactive.

             or

          Each donor unit used in the preparation of this
          material was NOT tested by an FDA approved method for
          the presence of the antibody to HTLV-III/LAV and
          therefore the HTLV-III/LAV antibody status of this
          material is unknown.

     2)   On the package and immediate reagent container state: 

          POTENTIAL BIOHAZARDOUS MATERIAL, see details in
          insert.

     3)   in the package insert:

          WARNING - POTENTIAL BIOHAZARDOUS MATERIAL

Because no test method can offer complete assurance that human
T-lympotropic virus type III/lymphadenopathy associated virus
(HTLV-III/LAV), hepatitis B virus, or other infectious agents are
absent, this specimen/reagent should be handled at the Biosafety
Level 2 as recommended for any potentially infectious human serum
or blood specimen in the Centers for Disease Control/National
Institutes of Health manual "Biosafety in Microbiological and
Biomedical Laboratories", 1984.

Biosafety Level 2 practices, equipment, and facilities are
applicable to clinical, diagnostic, teaching, and other
facilities in which work is done with the broad spectrum of
indigenous moderate-risk agents present in the community and
associated with human disease of varying severity.  With good
microbiological techniques, these agents can be used safely in
activities conducted on the open bench, provided the potential
for producing aerosols is low.  Hepatitis B virus, the
Salmonellae, and Toxoplasma spp. are representative of
microorganisms assigned to this containment level. Primary
hazards to personnel working with these agents may include
accidental autoinoculation, ingestion, and skin or mucus membrane
exposure to infectious materials.  Procedures with high aerosol
potential that may increase the risk of exposure of personnel
must be conducted in primary containment equipment of devices.

It is the intention of FDA that once the screening of donor units
for antibody to HTLV-III/LAV is required by regulation, and once
the current inventories of human reagent or control serums are
depleted by attrition, no HTLV-III/LAV antibody positive material
would be available or processed for the production of reagents
except where allowed by exemption.  Specific exemptions will be
granted upon request to those establishments who manufacture, for
example certain rare coagulation factor test substrates, or
positive control material for the HTLV-III/LAV antibody test
kits, or special research products.  Labeling of these products
should follow Center for Drugs and Biologics guidelines.

Products which are shipped in interstate commerce 30 days after
the date of this letter are considered subject to this guidance
unless specific exemption is granted by FDA.

Any product prepared from human blood, plasma, or serum should be
handled cautiously as a biohazardous material according to good
laboratory practices.  A general education effort by
manufacturers, professional associations, and government agencies
in the clinical laboratory profession concerning these practices
will be helpful in minimizing risks to people using these
materials.  W.,.. the cooperation of all manufacturers regarding
the above recommendations, and the cooperation of laboratory
professionals concerning implementation of good laboratory
practices, we can assure the public that all appropriate
precautions have been taken to minimize the risk of infections
from these materials.

No response to this letter is necessary, however, questions may
be directed to Jerome A. Donlon, M.D., Ph.D. (301) 427-7234.


Sincerely yours


John C. Villforth
Director
Center for Devices and Radiological Health