[Federal Register Volume 59, Number 109 (Wednesday, June 8, 1994)]
[Unknown Section]
[Page 0]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 94-13934]


[[Page Unknown]]

[Federal Register: June 8, 1994]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration
[Docket No. 94N-0169]

 

Assessment of Serum and Red Blood Cell Folate Methodology; 
Availability of Tentative Report; Announcement of Public Meeting

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice.

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SUMMARY: The Food and Drug Administration (FDA) is announcing the 
availability of a report entitled ``Tentative Report: Assessment of 
Serum and Red Blood Cell Folate Methodology Used in NHANES III.'' The 
report was prepared for FDA by the Life Sciences Research Office (LSRO) 
of the Federation of American Societies for Experimental Biology 
(FASEB). This document also announces a public meeting on the subject 
of the tentative report. The announcement of this meeting and the 
tentative report are intended to provide FDA with scientific 
information on the assessment of folate status in the U.S. population.

DATES: The public meeting on the subject of the tentative report will 
be held on July 15, 1994, 9 a.m., by LSRO/FASEB. Requests to make oral 
presentations at the open meeting must be submitted in writing and 
received by July 1, 1994. Scientific data, information, and views to be 
considered at the public meeting should be submitted on or before July 
12, 1994.

ADDRESSES: Submit written requests for single copies of ``Tentative 
Report: Assessment of Serum and Red Blood Cell Folate Methodology Used 
in NHANES III'' to LSRO/FASEB, 9650 Rockville Pike, Bethesda, MD 20814-
3998. Requests should be identified with the docket number found in 
brackets in the heading of this document. Send two self-addressed 
adhesive labels to assist that office in processing your requests. A 
copy of the tentative report is available for public examination at 
LSRO/FASEB (address above) and at the Dockets Management Branch (HFA-
305), Food and Drug Administration, rm. 1-23, 12420 Parklawn Dr., 
Rockville, MD 20857, between 9 a.m. and 4 p.m., Monday through Friday.
    Submit written requests to make oral presentations of scientific 
data, information, and views at the public meeting to LSRO/FASEB and to 
the Dockets Management Branch. Requests must be identified with the 
docket number found in brackets in the heading of this document. Two 
copies of the scientific data, information, and views should be 
submitted to each office.
    The public meeting will be held in the Chen Auditorium, Lee Bldg., 
FASEB, 9650 Rockville Pike, Bethesda, MD 20814-3998.

FOR FURTHER INFORMATION CONTACT:
    Kenneth D. Fisher, Life Sciences Research Office, Federation of 
American Societies for Experimental Biology, 9650 Rockville Pike, 
Bethesda, MD 20814-3998, 301-530-7030; or
    Jeanne I. Rader, Center for Food Safety and Applied Nutrition (HFS-
175), Food and Drug Administration, 200 C St. SW., Washington, DC 
20204-0001, 202-205-5375.

SUPPLEMENTARY INFORMATION: FDA has a contract (number 223-92-2185) with 
LSRO/FASEB concerning the analysis of scientific issues that bear on 
the safety of foods and cosmetics. The objective of this contract is to 
provide information to FDA on general and specific issues of scientific 
fact associated with the analysis of human nutrition.
    Analysis of serum and red blood cell (RBC) folate samples from 
Phase 1 (1988-1991) of the Third National Health and Examination Survey 
(NHANES III) was recently completed. These analyses were performed 
using a radioassay kit with 125-I-folate as the tracer. The radioassay 
kit that previously has been used to determine folate values is based 
on pteroylglutamic acid (PGA) standards, which were developed in 1975.
    In a 1993 report (Ref. 1), Levine reported that the folate data 
derived from the radioassay kits used for Phase 1 of NHANES III were 
about 30 percent higher than he would have expected based upon internal 
PGA standards prepared in his laboratory. He suggested that this 
discrepancy was related to differences between the standards in his 
laboratory and the standard values established in 1975 that have been 
provided with the radioassay kits (Ref. 1). According to Edwards (Ref. 
2), the folate radioassay kit introduced in 1975 was calibrated against 
the Lactobacillus casei microbiological assay which was the accepted 
standard at that time. The Centers for Disease Control and Prevention 
(CDC) and others have consistently confirmed Levine's finding. Thus the 
serum and RBC folate values derived by use of the radioassay kits in 
Phase 1 of NHANES III are likely to be high by a factor of about 30 
percent.
    Based on these results, CDC has recommended the use of an 
``adjustment'' factor to more accurately reflect the actual serum and 
RBC folate concentrations relative to corrected reference standards. 
This adjustment, however, may also require reconsideration of the 
interpretative criteria for evaluating the folate status of the U.S. 
population from blood samples from Phases 1 and 2 of NHANES III.
    FDA is announcing that it has asked FASEB, as a task under contract 
number 223-92-2185, to provide its Center for Food Safety and Applied 
Nutrition with an up-to-date scientific assessment of the methodology 
used in NHANES III to assess serum and RBC folate in the U.S. 
population. Specifically, FDA asked FASEB to address the following 
matters in its tentative and final reports: (1) Examine the analytical 
and biochemical bases for the discrepancies associated with serum and 
RBC folate values derived from use of the radioassay kits used in Phase 
1 of NHANES III, (2) evaluate the scientific basis and validity of the 
procedures recommended by CDC to make corrections to serum and RBC 
folate values obtained in Phase 1 of NHANES III, (3) re-examine current 
``cut-off'' values for estimation of ``deficient'' and ``low'' folate 
status in light of the need for application of a correction factor for 
survey sample values, (4) determine whether these approaches are still 
useful for estimating the prevalence of inadequate folate nutriture, 
and (5) obtain suggestions on approaches to addressing the 
comparability of the folate assays from Phase 1 and Phase 2 of NHANES 
III, and the comparability of the NHANES III data with those obtained 
in NHANES II. In response to this request, FASEB directed LSRO to 
obtain state-of-the-art scientific information about the analytical 
methodology and possible use of an adjustment factor for Phase 1 NHANES 
III serum and RBC folate data.
    LSRO has prepared a tentative report entitled ``Assessment of Serum 
and Red Blood Cell Folate Methodology Used in NHANES III'' (Ref. 3). 
Requests for a copy of the report should be made to LSRO/FASEB. 
Requests should be identified with the docket number found in brackets 
in the heading of this document. Send two self-addressed adhesive 
labels to assist that office in processing your requests. The tentative 
report will be on display at LSRO/FASEB and at the Dockets Management 
Branch (address above).
    FDA and FASEB are announcing that LSRO/FASEB will hold a public 
meeting on the report announced in this document on July 15, 1994. It 
is anticipated that the public meeting will not exceed 1 day depending 
on the number of requests to make oral presentations.
    Written requests to make oral presentations of scientific data, 
information, and views at the open meeting on the five issues given in 
this document must be submitted in writing to LSRO/FASEB and the 
Dockets Management Branch and received by July 1, 1994.
    FDA and FASEB are also inviting submission of written presentations 
of scientific data, information, and views on the issues identified 
above for this topic. These materials should be submitted on or before 
July 12, 1994. Two copies of the written material to be considered at 
the open meeting must be submitted to each office listed above.
    Pursuant to its contract with FDA, FASEB will provide the agency 
with a final report of its review and evaluation on or before September 
30, 1994.

References

    The following references have been placed on display in the Dockets 
Management Branch (address above) and may be seen by interested persons 
between 9 a.m. and 4 p.m., Monday through Friday.
    1. Levine, S., ``Analytical Inaccuracy for Folic Acid with a 
Popular Commercial Vitamin B12/Folate Kit,'' Clinical Chemistry, 
39(10):2209-2210, 1993.
    2. Edwards, R. B., ``Response,'' Clinical Chemistry, 
39(10):2210, 1993.
    3. ``Tentative Report: Assessment of Serum and Red Blood Cell 
Folate Methodology Used in NHANES III,'' Life Sciences Research 
Office, Federation of American Societies for Experimental Biology, 
Bethesda, MD, May 1994.

    Dated: June 3, 1994.
William K. Hubbard,
Acting Deputy Commissioner for Policy.
[FR Doc. 94-13934 Filed 6-3-94; 3:17 pm]
BILLING CODE 4160-01-F