[Federal Register Volume 61, Number 44 (Tuesday, March 5, 1996)]
[Rules and Regulations]
[Pages 8781-8797]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 96-5014]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
21 CFR Parts 136, 137, and 139
[Docket No. 91N-100S]
RIN 0910-AA19
Food Standards: Amendment of Standards of Identity For Enriched
Grain Products to Require Addition of Folic Acid
AGENCY: Food and Drug Administration, HHS.
ACTION: Final rule.
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SUMMARY: The Food and Drug Administration (FDA) is amending the
standards of identity for several enriched grain products and, by
cross-reference, the standards of identity for enriched bromated flour,
enriched vegetable macaroni, and enriched vegetable noodle products, to
require the addition of folic acid. The agency is requiring that these
products be fortified with folic acid at levels ranging from 0.43
milligrams (mg) to 1.4 mg per pound (mg/lb) or 95 micrograms
(g) to 309 g/100 grams (g), of product. These values
are based on a fortification level of 140 g/100 g (0.635 mg/
lb) of the cereal grain product. This action is being taken to help
women of childbearing age to reduce their risk of having a pregnancy
affected with spina bifida or other neural tube defects (NTD's) and to
comply with the recommendation of the U.S. Public Health Service (PHS)
that they consume at least 0.4 mg (400 g) of folic acid daily.
This action also responds to a citizen petition submitted by Glenn
Scott.
EFFECTIVE DATE: January 1, 1998.
FOR FURTHER INFORMATION CONTACT: Felicia B. Satchell, Center for Food
Safety and Applied Nutrition (HFS-158), Food and Drug Administration,
200 C St. SW., Washington, DC 20204, 202-205-5099.
SUPPLEMENTARY INFORMATION:
I. Background
Recent estimates state that there are approximately 4,000
pregnancies each year, including 2,500 live births, that are affected
by spina bifida and other neural tube defects. In September 1992, PHS
recommended that all women of childbearing age in the United States
consume 0.4 mg (400 g) of folic acid daily to reduce their
risk of having a pregnancy affected with spina bifida or other NTD's
(Ref. 1). Furthermore, PHS identified several possible approaches by
which folate intake by the target population could be increased. These
approaches included: (1) Improvement of dietary habits, (2)
fortification of the U.S. food supply, and (3) daily use of folic acid
supplements by women throughout their childbearing years. However, the
PHS recommendation cautioned against daily intakes of folate above 1
mg. A recognized adverse effect of high intakes of folate is a masking
of the anemia of vitamin B12 deficiency, allowing the neurologic damage
to progress untreated. PHS noted that care should be taken to keep
total folate consumption at less than 1 mg (1,000 g)/day,
except under the supervision of a physician (Ref. 1).
Following publication of the PHS recommendation, FDA convened a
Folic Acid Subcommittee from its Food Advisory Committee (hereinafter
referred to as the Folic Acid Subcommittee) to consider some of the
issues raised by the recommendation. After consideration debate, the
Folic Acid Subcommittee identified several approaches that might assist
women of childbearing age to increase their daily folate intake. These
approaches included: (1) Development of a fortification program such
that 90 percent of women of childbearing age could receive at least 400
g per day from all sources, while preventing
[[Page 8782]]
excessively high folate intakes by nontarget groups; (2) appropriate
labeling of foods, including dietary supplements; and (3)
implementation of an educational program directed primarily at women of
childbearing age that emphasizes the importance of folate intake before
pregnancy, and continuing into early pregnancy and its potential effect
on reducing the incidence of NTD's. (For a detailed discussion of the
issues and concerns raised by the Folic Acid Subcommittee please refer
to the Health Claims proposed rule (58 FR 23254 at 23256) and the final
rule authorizing a health claim about the relationship between folate
and neural tube defects (hereinafter referred to as the claims final
rule) published elsewhere in this issue of the Federal Register.)
After considering the suggestions of PHS and the Folic Acid
Subcommittee, FDA tentatively concluded that development and
implementation of a fortification program for the addition of folic
acid to the food supply could be an effective part of an overall plan
to increase the folate intake of women of childbearing age to assist
them in reducing their risk of having a NTD-affected pregnancy. Food
fortification, as noted by the Folic Acid Subcommittee and expert
speakers who testified before the Folic Acid Subcommittee, has the
advantage of reaching a great number of women in the target population
before conception and during early pregnancy. It also has the advantage
of providing folic acid in a continuous and passive manner and, thus,
represents a potentially effective means for improving the folate
nutriture of women throughout their childbearing years. However,
fortification must be controlled to ensure that daily intake of folate
by the target population, as well as by the general population, is no
more than 1 mg.
The issues raised by a fortification program were highlighted for
the agency in the Federal Register of October 14, 1993 (58 FR 53254),
in a document entitled ``Food Labeling: Health Claims and Label
Statements; Folate and Neural Tube Defects,'' (hereinafter referred to
as the folic acid health claims proposal) when it proposed to authorize
a health claim about the relationship between folate and the risk of
neural tube birth defects on the labels or in the labeling of foods and
dietary supplements. In the folic acid health claims proposal (58 FR
53254 at 53270), FDA acknowledged that authorizing a health claim on
folate and NTD's would create the likelihood that manufacturers would
fortify their products with folic acid so that they could qualify to
bear the claim, thereby increasing the possibility of uncontrolled
fortification of the food supply. Consequently, FDA said that any
fortification program that it adopted must be consistent with a safe
range of intake for all population groups and yet be capable of
maximizing the folate intakes of the target population within this safe
range.
The options that FDA considered for providing folic acid to women
of childbearing age through food fortification included the addition of
folic acid to cereal-grain products, fruit juices, and dairy products.
In weighing these options, FDA considered the effects of the inclusion
of folic acid in breakfast cereals and in dietary supplements. The
agency's decision to factor the amount of folic acid supplied by
breakfast cereals and supplements in its estimates of the effects of
fortification is fully discussed in the folic acid health claims
proposal (58 FR 53254 at 53276).
In determining the appropriate levels of fortification with folic
acid, the agency used the U.S. Department of Agriculture's (USDA's)
1987 to 1988 national food consumption data (Ref. 2) to estimate the
daily intake of folate for the target population, as well as for the
general population, with fortification at different levels for cereal-
grain products, dairy products, and juices. The agency estimated the
effects of fortification using three values: 70, 140, and 350
g of folic acid/100 g of cereal- grain product. As discussed
in the folic acid health claims proposal, the value of 70 g/
100 g (0.317 g/lb) is the amount recommended in 1974 by the
Food and Nutrition Board, National Research Council, National Academy
of Sciences, and would restore the folate lost in the milling of
cereal-grain products (Ref. 3). The value of 140 g/100 g is
twice that amount, and 350 g/100 g is five times that amount.
FDA's analysis showed that when fortification included fruit juices
and dairy products in addition to cereal-grain products, ready-to-eat
breakfast cereals, and dietary supplements, intakes by consumers in
some nontarget groups exceeded 1 mg/day even at the lowest level of
fortification. However, when fortification is limited to cereal-grain
products at levels of 70 g/100 g or 140 g/100 g,
estimates of daily intakes remained below 1 mg/100 g. At fortification
levels of 350 g/100 g, FDA estimated the daily intake to reach
levels of 1,220 g/day, which exceeds the recommended safe
upper limit.
The agency also estimated the daily intake of folate for consumers
who follow Federal government dietary guidance, such as the U.S.
Dietary Guidelines and the DHHS/USDA Food Guide Pyramid, and consume
cereal-grain products fortified with folic acid, to determine whether
these consumers will have daily intakes in excess of the recommended
safe upper limit of 1 mg/day.
These estimates showed that consumers who followed even the low-end
of recommendations from the USDA Food Guide Pyramid could, without
supplement use, easily consume 420 g or more of folate per day
from cereal-grain products fortified with 70 g/100 g. Further,
such consumers' daily intake could triple if such products were
fortified with 350 g folic acid/100 g.
As a result of its analysis of fortification of several cereal-
grain, dairy, and juice products, FDA tentatively determined that
fortification should be limited to cereal-grain products and not
extended to dairy products and fruit juices. The agency noted that
intakes by very large segments of the general population could reach
several milligrams per day if all of these foods were fortified with
folic acid.
The agency also tentatively decided that the appropriate
fortification level for cereal-grain products was 140 g/100 g.
Based on the results of its analysis, FDA determined that fortification
of cereal-grain products with 140 g/100 g, along with
fortification of ready-to-eat breakfast cereals up to 100 g/
serving and dietary supplements up to 400 g per unit or per
serving, would provide increased intakes of folate for women in their
childbearing years, while keeping daily intakes for the nontarget
population within the recommended safe upper limit of approximately 1
mg/day. The agency noted that even with supplement use, 95th percentile
intakes by adults 51+ years of age could reach 840 to 860 g/
day if these enriched cereal-grain products are fortified with 140
g/100 g. While the agency recognized that this level
approached the recommended safe upper limit and did not take into
account likely underreporting biases regarding food intakes and
underestimation of folate content of foods, it tentatively concluded
that fortification of cereal-grain products with 140 g/100 g
folic acid was the most appropriate fortification level of the three
levels analyzed.
In addition to estimating daily intakes of folate at the levels
cited above, FDA reviewed the existing food additive regulation
Sec. 172.345 (21 CFR 172.345) governing the use of folic acid to
determine whether the regulation was adequate to ensure that addition
of folic acid to foods would be consistent with
[[Page 8783]]
the fortification proposals discussed above. As a result of its review,
FDA recognized that the existing regulation lacked the guidance
necessary for manufacturers to decide which foods are appropriate for
fortification, and the levels at which folic acid can be added. More
importantly, FDA realized that the regulation would not have limited
the addition of folic acid to enriched cereal-grain products, breakfast
cereals, and dietary supplements. In fact, the regulation as written
would have permitted folic acid addition to virtually any food.
Thus, in the same issue of the Federal Register that the agency
proposed to authorize a health claim about the relationship of folate
and NTD's (58 FR 53254 at 53270), it published a proposal entitled
``Food Additives Permitted for Direct Addition to Food for Human
Consumption, Folic Acid (Folacin)'' (58 FR 53312) (hereinafter referred
to as the food additives proposal) to amend the food additive
regulation to restrict the addition of folic acid to specific foods. In
that document, FDA proposed, among other things, to establish a
limitation on the addition of folic acid to breakfast cereals of 100
g folic acid per serving, to retain current limitations (i.e.,
400 g/daily) on the use of folic acid in dietary supplements,
and to permit the addition of folic acid to foods as authorized by the
standards of identity. The agency tentatively concluded that such
action was necessary to establish safe conditions of use for folic acid
in the food supply and still assist the target population, women of
childbearing age, to achieve the goal recommended by PHS that they
consume at least 400 g of folate per day.
Also, in the October 14, 1993, issue of the Federal Register, FDA
published a proposal entitled ``Food Standards: Amendment of the
Standards of Identity for Enriched Grain Products to Require Addition
of Folic Acid,'' (58 FR 53305) (hereinafter referred to as the
standards of identity proposal) to amend the following standards of
identity to require the addition of folic acid at a fortification level
of 140 g/100 g: enriched bread, rolls, and buns (Sec. 136.115
(21 CFR 136.115)); enriched flour (Sec. 137.165 (21 CFR 137.165));
enriched self-rising flour (Sec. 137.185 (21 CFR 137.185)); enriched
corn grits (Sec. 137.235 (21 CFR 137.235)); enriched corn meals
(Sec. 137.260 (21 CFR 137.260)); enriched farina (Sec. 137.305 (21 CFR
137.305)); enriched rice (Sec. 137.350 (21 CFR 137.350)); enriched
macaroni products (Sec. 139.115 (21 CFR 139.115)); enriched nonfat milk
macaroni products (Sec. 139.122 (21 CFR 139.122)); and enriched noodle
products (Sec. 139.155 (21 CFR 139.155)) and, by cross-reference, the
standards of identity for enriched bromated flour (Sec. 137.160 (21 CFR
137.160)), enriched vegetable macaroni products (Sec. 139.135 (21 CFR
139.135)), and enriched vegetable noodle products (Sec. 139.165 (21 CFR
139.165)).
FDA received approximately 170 letters in response to its proposal
to amend the standards of identity for enriched cereal-grain products
to require folic acid fortification at 140 g/100 g. Each
letter contained one or more comments. The letters were from a wide
range of sources, including individual members of FDA's Folic Acid
Subcommittee and Food Advisory Committee, Federal and State Government
agencies, a foreign government, health care organizations, academia,
consumer organizations, medical professionals, consumers, industry, and
industry trade associations. Some comments supported various provisions
of the proposal. Other comments suggested modifications, revisions, or
revocations of various provisions of the proposal. Some comments raised
concerns that were more germane to issues discussed in the folic acid
health claims and food additive proposals. These comments were
forwarded to the appropriate dockets for response. Some comments raised
issues that were outside the scope of this rulemaking and will not be
addressed in this final rule. A summary of the relevant comments, the
agency's responses to the comments, and a complete discussion of the
agency's conclusions with respect to the fortification of enriched
cereal-grain products follow.
II. Comments and Agency Response
A. Fortification
1. The majority of comments recognized the need to assist women of
childbearing age to increase their daily intake of folate to reduce
their risk of an NTD-affected pregnancy. Many of these comments agreed
with the PHS' and Folic Acid Subcommittee's recommendations that
fortification of the food supply is an appropriate approach to achieve
this goal. Several comments, however, opposed the use of fortification
as a mechanism to address this need. Some of the comments opposed
fortification because of uncertainties in the efficacy data. These
comments stated that the available data do not indicate what minimum
level of folate is needed to effect a significant reduction in NTD's,
and they argued that, therefore, the decision to fortify is premature.
These comments suggested that the agency wait until additional studies
have been completed that better define the minimum level of folate
needed to be effective or that identify other alternatives that would
be effective in increasing the daily folate intake of the target
population.
While FDA recognizes that there is some uncertainty in the
literature as to the optimal intake of folate required to reduce the
risk of NTD's, PHS, in examining the data from the available human
studies, found the evidence sufficiently consistent to make its
recommendation that all women capable of becoming pregnant should
consume 400 g folic acid daily. This target intake goal
represents the best scientific judgment based on available data. It has
also been supported by the Folic Acid Subcommittee.
Furthermore, PHS, the Folic Acid Subcommittee, as well as other
medical experts, recommended food fortification as part of an overall
program to improve the folate intake of women of childbearing age. This
recommendation is based on the fact that 50 percent of pregnancies are
unplanned, and that a large segment of women in the target group will
not use folic acid supplements daily. Thus, a passive means of ensuring
that these women have adequate folate intake is important. The comments
that opposed fortification did not submit any data in support of their
position. Thus, the agency has no basis to reject the recommendations
of PHS and the Folic Acid Subcommittee to develop a folate
fortification program to assist women of childbearing age in consuming
at least 400 g/day.
Although the agency is aware that there are several ongoing studies
on the relationship between folate and NTD's, it has not been persuaded
by the comments to wait until additional studies have been completed to
determine what minimum level of folate intake is likely to be
effective. The agency has confidence in the data that suggest that at
intake levels of 400 g/day, the incidence of NTD's can be
reduced. Thus, the agency concludes that it would not be in the best
interest of women in the target group to wait until these studies are
completed and reviewed before implementing a program to assist them in
increasing their daily intake of folate.
The evidence that is available supports the position that the
consumption of folate plays an important role in reducing the risk of
neural tube birth defects. Weighing this evidence and recognizing that
the majority of women in the target population do not consume the
levels of
[[Page 8784]]
folic acid recommended to reduce the risk of neural tube birth defects
(Ref. 1), the agency concludes that it is appropriate to implement a
fortification program at this time.
Further, the agency is concerned that without the limitations that
it is adopting in this final rule, and in the final rule entitled
``Food Additives Permitted for Direct Addition to Food for Human
Consumption; Folic Acid (Folacin)'' (hereinafter referred to as the
food additives final rule) which is published elsewhere in this issue
of the Federal Register, to control the addition of folic acid to the
food supply, the authorization of the health claim about folate and
NTD's may encourage overfortification of the U.S. food supply and
increase the risk of overconsumption of folate. Because the current
food additive regulation does not limit or specify the types of foods
that can be fortified with folic acid, approval of the claim, without
any other action by the agency, could encourage manufacturers to
fortify a variety of foods to qualify the food for a health claim.
Consequently, without proper control over the types of foods that can
be fortified with folic acid, overfortification could result.
The amendment to the standards of identity for enriched cereal-
grain products to require the addition of folic acid at specific levels
will help to ensure that the addition of folic acid to the food supply
is done in a safe, rational, and reasonable manner because it will
limit the number of foods that can be fortified and limit the level of
fortification. The levels of fortification established in this final
rule, coupled with the provisions governing addition of folic acid to
nonstandardized foods established in the food additives final rule,
will meet the goal of increasing folate intake among women of
childbearing age while keeping the daily consumption of folate below
the safe upper limit of 1 mg/day.
2. Comments that opposed fortification asserted that consumers
believe that fortification as proposed denies freedom of choice and
control over daily folate intake and is, therefore, viewed as an
attempt to medicate people without obtaining informed consent. These
comments further asserted that fortification, as proposed, subjects
them to the risk of overconsumption. As an alternative, these comments
suggested that the effort to increase dietary folate intake in the
target population focus on the use of dietary supplements because the
amount of intake can be better controlled. They suggested that FDA work
with other public health service agencies to establish policy
initiatives equivalent to those used by the food and dietary supplement
industries to market their products.
The agency disagrees with these comments. The agency is providing
for fortification with folic acid only in the standards of identity for
enriched cereal-grain products. Unenriched cereal-grain products
without folic acid will continue to be available. Consumers will be
able to select foods made with the unenriched version of the product if
they wish to avoid folic acid. Furthermore, the estimated daily intakes
that will result from the level of fortification established in this
final rule are well below the level of folic acid traditionally used to
treat persons with folate deficiency. Therapeutic dosages of folic acid
used for treatment of folate deficiency are generally in the range of 1
to 5 mg/day and are administered under the supervision of a physician.
Therefore, the comments that suggest that fortification of enriched
cereal-grain products is an attempt to medicate the U.S. population
simply have no basis in fact.
Furthermore, the intakes that are likely to result from the level
of fortification established in this final rule do not present a health
concern to the general population, especially in conjunction with the
provisions of the food additive final rule published elsewhere in this
issue of the Federal Register. FDA has projected the total daily intake
of folate that is likely to result from the levels of fortification
that FDA is requiring and determined that it is well within the safe
upper limit of intake. Moreover, cereal-grain products have a long
history of being vehicles for improving the nutrient intake of the U.S.
population. FDA requires the addition of niacin, thiamin, and
riboflavin in the standards of identity for enriched cereal-grain
products to improve the daily intake of these nutrients. Fortification
of these products was instrumental in reducing the prevalence of
diseases related to insufficient intake of these vitamins.
In response to the comments that suggested that FDA rely on the use
of dietary supplements to increase daily folate intake, the agency
notes that in requiring the fortification of enriched cereal-grain
products, it is not discounting the use of dietary supplements to
assist women in the target group to increase their daily folate intake.
In fact, the agency included the use of dietary supplements in its
estimates to determine the appropriate level for fortification of
enriched cereal-grain products. However, the agency is not confident
that the use of dietary supplements alone will be sufficient to reach
the target population when folate intake is critical (i.e., before and
during the first 6 weeks of pregnancy).
During the first 6 weeks of pregnancy many women are not even aware
that they are pregnant and would likely not be under the care of a
physician. Thus, as stated in several comments, there would be no
reason to expect the many women who do not normally take supplements
daily to be motivated to change this behavior. Therefore, supplement
use cannot be relied on as the sole source for increasing dietary
folate intake. As discussed above, the use of fortification of cereal-
grain products has the advantage of providing folic acid in a
continuous and passive manner and, therefore, should be an effective
means for improving the folate nutriture of women in their childbearing
years.
3. A few comments opposed to fortification suggested that, as an
alternative, FDA encourage women in the target group to increase their
daily folate intake by increasing consumption of foods that naturally
contain high levels of folate such as blackeye peas.
While FDA finds merit in the comments' suggestion to encourage
women in the target group to increase their daily folate intake by
increasing their consumption of foods naturally high in folate, the
agency is not persuaded that such action makes food fortification
unnecessary. The dietary guidance suggested by the comment can be used
in conjunction with food fortification, as part of a program designed
to help women in the target group to increase their daily folate
consumption. A health claim about the relationship between folate and
NTD's on a food that qualifies to bear the claim will contribute to
such a program, regardless of whether the food naturally qualifies to
bear the claim or qualifies on the basis of its fortification level. In
addition, foods that naturally contain folate and qualify to bear a
health or nutrient content claim are likely to be highlighted as a
source of this nutrient. Such claims will encourage women in the target
group to select these foods as a part of their diet.
Most significantly, however, given the value of adequate folate
intake by women of childbearing age and given the value of a program
that allows women to obtain adequate folate by simply consuming such
staples as bread and rolls, FDA sees no reason not to require
fortification of such foods, even though foods exist that are naturally
high in folate.
4. Some comments opposed to fortification opined that fortification
[[Page 8785]]
would not assure physicians and health care professionals that their
patients are obtaining adequate amounts of folate from the food supply
because the bioavailability of folate in foods is 25 to 75 percent
depending on the food.
As discussed in the folic acid health claims proposal, FDA
considered several issues in developing its options for fortification.
With respect to issues of bioavailability, FDA concluded that
bioavailability cannot be meaningfully factored into fortification
scenarios because issues of bioavailability are very complex, and no
systematic data are available on many of the factors that affect
bioavailability. Consequently, the estimates developed by FDA focused
more on consumption patterns of various staple foods, and their
availability and use in the U.S. food supply, than on the
bioavailability of folic acid from a specific food.
The comment did not provide information to persuade the agency that
the complexity associated with bioavailability would significantly
reduce the effectiveness of food fortification as part of an overall
effort to improve folate nutriture among women in the target group.
5. Two comments recommended revising the proposal to require the
addition of vitamin B12 in a one-to-one ratio with folic acid. The
comments contended that doing so will not only prevent vitamin B12
deficiency, but it will also prevent the masking effect that may be
caused with high consumption of folate. One comment urged FDA to design
research that will determine the safety and effectiveness of fortifying
the food supply with vitamin B12 along with folic acid because
such fortification could eliminate the adverse effect of folate on
vitamin B12 deficiency.
The agency is not persuaded that the approach suggested by these
comments addresses all of the safety concerns relating to persons with
vitamin B12 deficiencies. As fully discussed in the food additives
final rule, FDA rejects this recommendation because the available data
do not establish that requiring the addition of vitamin B12
whenever folic acid is added will eliminate the safety concerns
relating to persons with vitamin B12 deficiencies that arise
because of deficiencies in intrinsic factor (pernicious anemia) or
other B12-related deficiencies.
6. Two comments opposed to fortification stated that FDA should
take the same position with respect to folic acid fortification that it
did when it decided not to fortify foods with iron in the 1970's
because of the concern about iron storage diseases.
While the agency acknowledges that it considered taking a similar
approach to increase the amount of iron provided by the diet when it
proposed to double the amount of iron added to enriched cereal-grain
products, the agency did not finalize that proposal because of
significant safety concerns regarding the risk of iron storage
diseases. Rather, the agency retained the existing level of iron
fortification for cereal-grain products. The agency does not have
similar safety concerns about the level of folic acid fortification
that it is requiring in this final rule because it has concluded, based
on a safety review (as fully discussed in the food additives proposal
and final rule), that this required level is safe and will not result
in overconsumption of folate.
B. Covered Products
7. Some comments stated that dietary consumption studies indicate
that women of reproductive age are less likely than other groups to
consume enriched cereal-grain products that conform to a standard of
identity, and that, therefore, the use of such foods as a vehicle for
folic acid fortification would not significantly affect the risk of
NTD's. These comments argued that, instead, fortifying these foods will
only increase the amount of daily folate intake among the nontarget
groups.
In selecting cereal-grain products as vehicles for fortification,
the agency started with the basic principle that fortification of
staple products that are commonly consumed in significant amounts by
virtually all members of the target population is most likely to result
in increased intakes of a specific nutrient by the target population.
Although the agency recognizes that current survey data suggest that
consumption of enriched grain products may be somewhat lower in the
target population than in other groups, these foods still are reported
to be consumed on a daily basis by more than 90 percent of women of
childbearing age (Ref. 4). In addition, data show that the difference
between target and nontarget populations in consumption of other foods
considered as fortification vehicles, such as dairy products and
juices, is even greater (Ref. 4). Therefore, the other foods would be
no more appropriate as fortification vehicles for maximizing folate
intake by the target group, and yet maintaining safe consumption by
nontarget groups, than cereal-grain products.
The agency notes that cereal-grain products were recommended by the
Food and Nutrition Board in its 1974 report on food fortification as
fortification vehicles because of the patterns of consumption of these
foods. In addition, enriched cereal-grain products have a long history
of being successful vehicles for improving the nutriture of the U.S.
population and for reducing the risk of nutrient deficiency diseases.
Thus, the agency concludes that enriched cereal-grain products are an
appropriate vehicle to increase daily folate intake among women of
childbearing age. In fact, the estimates that FDA developed in
evaluating options for folic acid fortification demonstrate that the
addition of folic acid to enriched cereal-grain products, coupled with
the addition of this nutrient to breakfast cereals and dietary
supplements, will help to significantly increase the daily folate
intake of women in the target group (see Table 7 of 58 FR 53254 at
53295)).
Furthermore, increasing awareness of the role of folate in reducing
the risk of neural tube birth defects through the use of health claims
and other educational initiatives should encourage women in the target
group to increase their daily folate intake by consuming folate
containing foods, including enriched cereal-grain products. Consumption
of cereal-grain products is also likely to be influenced by current
dietary guidelines that promote increased consumption of these foods.
8. Other comments requested that FDA permit the addition of folic
acid to other cereal-grain products such as whole grain flours, breads,
cereals, macaroni products, rice, and grits and not just the enriched
cereal-grain foods that conform to a standard of identity. The comments
argued that without these products being fortified, consumers may be
encouraged to eat enriched refined grains instead of their whole grain
counterparts and consequently follow dietary patterns that are
inconsistent with current dietary guidelines to eat whole grain
products.
FDA did not propose to provide for the addition of folic acid to
whole grains or products from whole grains because, traditionally,
these products are not enriched. Whole grain wheat products naturally
contain higher levels of the B vitamins, including folate, because the
germ and bran layer are not removed when the wheat kernel is processed.
FDA's standards of identity for cracked wheat, crushed wheat, and whole
wheat flour, in Secs. 137.190, 137.195, and 137.200, respectively,
state that the proportions of the natural constituents of such wheat,
other than the moisture, remain unaltered by the manufacturing process.
In establishing the standards of identity for the enriched cereal-grain
products, the agency's initial goal was to
[[Page 8786]]
restore thiamin, niacin, and riboflavin, nutrients that are removed
when the bran layer and germ are removed during the processing of
wheat. Subsequently, the agency required the addition of iron to the
enriched grain and also provided for the optional addition of other
nutrients, such as calcium and vitamin D.
The estimates that the agency has relied on in selecting a
fortification level of 140 g/100 g considered only
fortification of breakfast cereals, dietary supplements, and
standardized enriched cereal grain products and did not include
fortification of other nonstandardized or unenriched standardized
cereal-grain products. Consequently, including such foods in the
fortification program could result in a daily intake of folate that is
above the safe upper limit of 1 mg/day. Thus, the agency is not
persuaded by the comment that other cereal-grain products should be
fortified with folic acid.
With regard to the concern raised in the comment that fortification
of enriched cereal grain products may encourage consumers to choose
these products over their whole grain counterparts, the comment did not
provide any support for its concern. The decision to fortify enriched
cereal grain products at the level of 140 g/100 g is based on
current dietary consumption patterns. The agency is not persuaded by
the comments that the addition of folic acid will significantly change
consumption patterns of the target population. There is no evidence
that women will suddenly start consuming enriched products instead of
whole grain foods. In fact, one reason the agency has decided to
require the fortification of enriched cereal-grain products is to
enable women of childbearing age to significantly increase their daily
folate intake without changing their dietary habits. Finally, the
agency notes that while current dietary recommendations do encourage
increased consumption of whole grain foods, they also encourage
consumption of all cereal-grain products.
9. One comment expressed concern that the agency's tentative
decision to fortify cereal-grain products was unfair to the cereal-
grain industry because it singled out one segment of industry to
address a health concern. (The agency notes that the comment was not
submitted by a member of the cereal grains industry.)
As discussed in the folic acid health claims proposal, FDA
considered several options that included fortification of dairy
products and juices before concluding that the most appropriate option
was to limit fortification to enriched cereal-grain products. Aside
from the fact that these products have a long history of successful use
as vehicles for increasing nutrient intake among U.S. consumers,
consumption data and other relevant information reviewed by the agency
show that these products are consumed routinely on a daily basis by 90
percent of women in the target group. Furthermore, some comments
submitted to the docket by representatives of the cereal grains
industry stated that, generally, these products can be easily fortified
with folic acid. Therefore, FDA concludes that the enriched cereal-
grain products are the appropriate foods for fortification, and that
fortification of these products is not unfair to the industry.
C. Fortification Level
10. In the standards of identity proposal, FDA requested comments
on whether the proposed fortification levels discussed for enriched
cereal-grain products were appropriate. Comments responding to this
issue were varied. Some comments that supported fortification of
cereal-grain products stated that the proposed levels were too low to
have any appreciable effect on reducing the risk of NTD's in the target
population. One of these comments urged the agency to revise its
proposal and require fortification at levels of at least 210
g/100 g. However, the majority of these comments recommended
that FDA require fortification of folic acid within the range of 250 to
350 g/100 g. In support of their position, these comments
contended that this range was well within limits for safety and should
not mask the effects of vitamin B12 deficiency. One comment
further argued that at a fortification level of 350 g/100 g,
95 percent of persons in the nontarget population would not consume
more than 1 mg per day. One comment recommended 400 g/100 g
for cereal-grain products. This comment argued that fortification of
enriched cereal-grain products should be at the same level as dietary
supplements.
However, supplemental comments submitted by a majority of the
organizations supporting a higher fortification level, stated that
implementing fortification at a level of at least 140 g/100 g
will constitute a critically important step forward for the health of
American children. Some of these comments further stated that
fortification with at least 140 g/100 g will be the most
efficient and cost-effective approach to ensuring that women of
childbearing age consume the level of folic acid recommended to reduce
the risk of having a neural tube defect affected pregnancy.
The agency agrees with the latter comments. As discussed in the
folic acid health claims proposal (58 FR 53254 at 53279), fortification
of cereal-grain products at 140 g/100 g will produce a
significant increase in daily folate intake, even for women who make
food choices from the ``low'' range of the USDA Food Guide Pyramid and
consume only 5 servings/day of cereal-grain products and 1 bowl of
cereal containing a minimum of 100 g of folic acid. From these
sources alone, these women will consume about 320 g of folic
acid. Addition of a serving or two of vegetables, or of a serving of
fruit, will provide them with a folate intake above 500 g/day.
Thus, fortification of cereal-grain products at 140 g/100 g is
an important step in assisting women of childbearing age achieve the
PHS recommendation of consuming 400 g.
However, if cereal-grain products were fortified at 350 g/
100 g, and the dietary choices indicated above were made, a ``low''
consumer would obtain 610 g folic acid daily from these
sources alone. Thus, at a fortification level of 350 g/100 g a
``high'' consumer could reach intakes of folic acid of more than 1 mg/
day from bread, noodle, rice, and pasta products alone. Additional
consumption of breakfast cereals, fruits, vegetables, and a dietary
supplement by ``high'' consumers could result in daily intakes of
folate of about 2.5 mg/day, a level significantly above the safe upper
limit of daily intake of 1 mg.
The comments supporting fortification of enriched cereal-grain
products at levels above 140 g/100 g did not provide any
information to the agency that it had not considered in developing its
proposed rules. Nor did the comments offer alternative fortification
schemes that would allow addition of folic acid to enriched cereal-
grain products at levels exceeding 140 g/100 g yet limit the
daily intake of folate to levels that are within the safe upper limit
of 1 mg/day. Consequently, FDA disagrees with those comments that
suggested that enriched cereal-grain products be fortified at levels of
at least 210 g/100 g. There simply is no evidence in the
record that such a fortification program would keep folate intakes
within the safe upper limit.
Accordingly, as proposed, the agency is requiring the addition of
folic acid to enriched cereal grain products at a fortification level
of 140 g/100 g. FDA concludes that 140 g/100 g is the
maximum level of fortification of enriched cereal-grain products that
would be safe for all groups.
[[Page 8787]]
Nonetheless, as the agency states in the final rule on the use of
folic acid as a food additive, which is published elsewhere in this
issue of the Federal Register, given the nature of the support for
higher folic acid fortification levels in the comments, if evidence
becomes available to support that there is a reasonable certainty of no
harm at folate intakes above 1 mg/day, FDA would be willing to
reconsider the fortification levels that it is adopting and to consider
raising those levels.
11. Other comments opposed fortification at the proposed level of
140 g/100 g on the grounds that it is too high. These comments
asserted that such fortification may increase the risk of consuming
folate at levels in excess of the safe upper limit of 1 mg/day in a
substantial portion of the general population. Some of these comments
suggested that FDA consider the lower fortification level of 70
g/100 g in conjunction with an educational campaign that could
still be effective in reducing the risk of NTD's yet not pose the risk
of daily consumption of folate in excess of 1 mg/day.
In support of their position, some of these comments noted that the
Food and Nutrition Board recommended the fortification of cereal-grain
products at 70 g/100 g to restore folate lost in the milling
of cereal-grain products. Another comment supporting fortification at
the restoration level contended that such action would permit
additional restorations of nonstandardized foods such as breakfast
cereals. One comment from a foreign government questioned FDA's
decision to require folic acid fortification of all enriched cereal-
grain products when the data do not clearly establish the effectiveness
and safety of the proposed intervention program. However, the comment
suggested support of the Food and Nutrition Board's 1974 proposal for
cereal grain fortification, i.e., fortification with folic acid at 70
g/100 g.
In the standards of identity proposal, FDA tentatively concluded
that fortification of cereal-grain products with 140 g/100 g
folic acid was the most appropriate fortification level of the three
levels analyzed to ensure that folate intakes by the target population
would increase. The comments have not persuaded the agency that a
fortification level of 70 g/100 g could be as effective in
assisting women in the target population to achieve the PHS recommended
daily intake of 400 g. In fact, at a fortification level of 70
g/100 g, the estimated daily folate intake by ``low''
consumers among women of childbearing age is not likely to reach the
PHS recommended levels of 400 g/day without changes in their
food selection practices (see Table 4 of 58 FR 53254 at 53292). While
the agency must ensure that the use of folic acid in the food supply is
safe, it must also provide as great an opportunity as is prudent and
rational for all women of childbearing age to increase their intake to
the recommended level. The agency concludes that a level of 140
g/100 g is the most appropriate fortification level for
enriched cereal-grain products because, based on the results of its
estimated daily intakes, fortification at this level will provide daily
intakes for the nontarget population that remain within the recommended
safe upper limit of 1 mg/day, while providing increased intakes of
folate for women in their childbearing years (see Table 7 of 58 FR
53254 at 53295).
The agency notes, however, that it has reconsidered its proposed
fortification level for breakfast cereals. As fully discussed in the
food additives final rule, published elsewhere in this issue of the
Federal Register, FDA is permitting breakfast cereals to contain up to
400 g of folic acid per serving. As explained in that
document, the estimates for total daily folate intake that FDA
presented in the folic acid health claims proposal were based on the
assumption that all breakfast cereals were fortified at 400 g/
serving. Based on those estimates, daily folate intake for certain
groups in the nontarget population could exceed the recommended safe
upper limit of 1 mg/day. Currently, however, only about 3 to 6 percent
of breakfast cereals fortify at 400 g/serving. The agency has
found no reason to expect that this percentage will change and,
therefore, considers it unlikely that daily folate intake in the
nontarget population will exceed 1 mg with the fortification program
adopted in this final rule and in the food additives final rule.
D. Optional Versus Mandatory
Because of the increased health risk to persons with vitamin B
12 deficiency caused by increased levels of folate intake, FDA
solicited comments in the standards of identity proposal on whether the
addition of folic acid to enriched cereal-grain products should be
required as proposed or made optional.
12. A few comments fully supported the agency's proposal to require
folic acid addition to the enriched cereal-grain products. These
comments contended that required addition of folic acid was an
appropriate means of increasing the daily folate intake of women in the
target population. However, the majority of the comments that responded
to this issue stated that fortification should be voluntary. The
comments cited varied reasons in support of their position. Some
comments stated that the addition of folic acid to enriched cereal-
grain products should be optional pending further evidence that the
benefits outweigh the risk of masking vitamin B12 deficiency.
These comments contended that mandatory fortification of a wide variety
of common products may create difficulty for people wishing to avoid
folic acid. Furthermore, the comments asserted that FDA failed to
establish why mandatory fortification would be necessary given that
under current regulations voluntary fortification of standardized foods
with folic acid is prohibited.
Other comments recommended optional fortification so that millers
will not have to change their enrichment premixes for the general flour
supply, thereby minimizing the costs associated with fortification,
i.e., label changes, analytical testing, and inventory and supply
coordination, especially for products exported to countries that do not
permit folic acid fortification. The comments also stated that
voluntary fortification would facilitate compliance with the various
State enrichment laws.
A few comments opposed to mandatory fortification stated that FDA
failed to offer information as to why voluntary fortification would not
be sufficient to accomplish the public health goal of decreasing the
incidence of pregnancies with neural tube birth defects. The comments
urged FDA to establish a voluntary fortification program for enriched
cereal-grain products and to reassess the need for a mandatory
fortification in several years. One of these comments acknowledged,
however, that it is difficult to predict the extent of voluntary
fortification.
A small number of comments supported voluntary fortification for
only the enriched noodle and macaroni products. The comments contended
that voluntary compliance is consistent with FDA's current standards of
identity for enriched noodle and macaroni products with regard to
vitamin D, calcium, and wheat germ.
The agency does not agree with the comments that argued that the
fortification of enriched cereal-grain products should be voluntary. In
accepting the PHS' and Folic Acid Subcommittee's recommendation to
include fortification as part of an overall plan to increase the folate
nutriture of women of childbearing age, FDA has concluded that in order
for a fortification program to be effective,
[[Page 8788]]
fortification must be mandatory for the enriched cereal-grain products.
FDA is concerned that if it made fortification voluntary, and voluntary
fortification were not widespread, there would be only a negligible
increase in the daily folate intake of the target group, and the intent
of this rulemaking would have been defeated. FDA finds that there is a
public health need for women in their childbearing years to have
adequate folate intake, and that the only way that it can ensure that
they will have such an intake is through mandatory fortification.
FDA has traditionally used mandatory fortification to restore
nutrients lost during the processing of cereal grains and thereby to
address the need for reducing the risk of certain vitamin deficiency-
related problems. The comments have not persuaded the agency that the
same basic approach should not be applied in this case, where low
folate intake represents a risk factor for a neural tube defect-
affected pregnancy. USDA consumption data show that 90 percent of women
of childbearing age consume cereal-grain products. Thus, mandatory
fortification of cereal grains will, as stated above, increase folate
intake among the target group, without requiring significant change in
dietary patterns. Consequently, mandatory fortification of enriched
cereal grains will help to ensure that the daily intake among the
target group will reach the PHS recommended level of 400 g.
Voluntary fortification does not offer the same likelihood that folate
intake will result in intakes that approach the PHS recommendation
because the decision to fortify with folic acid will be at the
discretion of individual manufacturers. Therefore, voluntary
fortification will not adequately address the need for increased folate
intake among women of childbearing age.
FDA derived the fortification levels established in this final rule
based in part on a safe upper limit of 1 mg folate/day. The agency has
concluded that mandatory fortification of the enriched cereal-grain
products at the levels provided in this final rule is not likely to
increase the risk of ``masking'' anemia in vitamin B12 deficient
persons. Thus, the fortification program that FDA is adopting will help
to ensure that the amount of folate that people in all groups of the
population can reasonably be expected to consume will not exceed 1 mg/
day. As discussed in the food additives final rule, the agency has
examined the available data on the levels of folate that may mask
anemia of vitamin B12 deficiency and concluded that a daily intake
of up to 1 mg of folate is safe.
In response to concerns raised by millers regarding label changes,
analytical testing, and inventory and supply coordination, FDA
recognizes that manufacturers will need ample time to implement the
changes required by this amendment of the standards of identity. As
discussed below in the effective date section, FDA is permitting
manufacturers time to coordinate any necessary changes that need to be
made throughout the chain of food production to comply with the
requirements established in this final rule as well as with the
requirements set out in part 101 (21 CFR part 101).
The agency notes that manufacturers will continue to have the
option of using unenriched cereal-grain products as ingredients in
foods and to add enrichment nutrients to those products as they choose.
Several comments from industry representatives raised a concern that
the provisions in the food additive proposal would not permit addition
of folic acid at the bakery site. To the contrary, as discussed in the
food additives final rule, FDA will permit addition of folic acid at
the bakery site as long as it is in compliance with the governing
standard of identity. Consequently, manufacturers will have the same
option of adding folic acid as they have with other enrichment
nutrients when preparing foods that are made with unenriched cereal-
grain ingredients. The agency notes, however, that any products
marketed as a standardized enriched cereal-grain product will have to
contain folic acid at the levels established in this final rule, and
that these requirements preempt state enrichment requirements that are
not identical (see section 403(a) of the act (21 U.S.C. 343(a))).
With regard to exported products, the agency recognizes that
manufacturers may be required to maintain separate inventories for
foreign and domestic sales. While FDA recognizes the importance of
reducing trade barriers, its first obligation is to protect and promote
the health of U.S. consumers. In that regard, the agency concludes
that, because the fortification program adopted in this final rule is
necessary to significantly reduce the incidence of neural tube defect
affected pregnancies, it would not constitute an illegal trade barrier.
E. Other Issues
13. One comment from a consumer interest group recommended that if
research and monitoring does not establish in the next 2 years that the
risk of increasing folate intakes is significant for persons affected
with vitamin B12 deficiency or any folate-related diseases, then
FDA should increase the fortification levels in grain products or other
foods and require that upper safe limits be disclosed in higher dose
products. This comment urged FDA to initiate a rulemaking to restore
refined grain products with most of the vitamins and minerals that are
removed during milling as recommended by the Food and Nutrition Board
in 1974. The comment stated its belief that such an approach would
raise few safety concerns and would not be costly because manufacturers
are already equipped to add nutrients to food.
FDA cannot at this time commit to increasing the levels of folic
acid that may be added to food within the next several years. However,
as stated above, should data become available that demonstrate that
modifications need to be made to improve the effectiveness of the
intervention program, and evidence be developed that the safe upper
limit can be raised, FDA will decide what action is necessary. The
agency notes, however, that the action it is taking in this rulemaking
will more than compensate for the amount of folate lost during the
milling process.
As for the comment's request that FDA initiate rulemaking to
restore to refined grain products other vitamins and minerals that are
removed during milling raises, the agency notes that the request issues
outside the scope of this rulemaking. Therefore, no action on this
request is appropriate at this time.
14. Several comments raised concern regarding the impact of the
proposed regulation on foreign trade. One comment from a foreign trade
association urged FDA to delay finalizing the proposed regulation to
provide the International Harmonization Working Groups the opportunity
to review the proposal and recommend a strategy that would serve public
health goals, while achieving the spirit and intent of the North
American Free Trade Agreement (NAFTA). Another comment stated that the
extra costs and inherent inefficiencies of separate production runs
could preclude some manufacturers from the export marketplace.
Other comments stated that the lack of consistent requirements for
folic acid fortification between major trading partners, e.g., the
United States and Canada, would create problems in cross-border trade
and could result in higher costs for both U.S. and foreign consumers.
Furthermore, these comments asserted that inconsistent requirements
could reduce the competitiveness of domestic
[[Page 8789]]
manufacturers who export their products. Thus, the comments urged FDA
to resolve the issue of exporting folic acid enriched products to
foreign countries by working with foreign governments to permit export
of folic acid-enriched food.
FDA recognizes that the provisions it is adopting in this final
rule may be inconsistent with the fortification policies of other
countries. However, as discussed above, the agency finds that the
action that it is taking in this final rule is necessary to adequately
protect the public health of U.S. consumers. FDA will continue to work
with officials in other countries, particularly parties to NAFTA, to
find ways to reduce barriers to cross-border trading of cereal-grain
products and other foods.
F. Specific Standards of Identity
In this document, the agency is providing for the addition of folic
acid at the level of 140 g/100 g to the individual enriched
cereal-grain products that are the subject of standards of identity.
The agency described indepth the method that it used in arriving at the
levels of addition for folic acid in the specific standards of identity
in the standards of identity proposal. FDA will not describe that
method again in this document except to the extent that clarification
is warranted in response to specific comments. For a complete
discussion of the basis on which FDA established the enrichment levels
for the subject standards of identity, the agency refers interested
persons to the standards of identity proposal (58 FR 53305 at 53307 to
53309).
1. Bakery and Wheat Flour Products
15. One comment, while supportive of the proposal to fortify
cereal-grain products, suggested that a range of levels be permitted
for addition of folic acid to all enriched cereal-grain products
because of the inherent variation in the addition of the vitamins, the
distribution of the vitamins in a food, and the analytical methodology.
The comment suggested that FDA permit the addition of folic acid within
a range of 24 to 35 percent over the amount established for each
individual standard. For example, the comment suggested that the
proposed amount of 0.7 mg/lb for enriched flour should be revised to
0.7 to 0.91 mg/lb. The comment argued that this scheme is the same as
that used for enrichment in the macaroni and noodle standards and is
needed for the same reasons that it is provided for in those standards.
FDA does not agree that it is necessary to provide for a range in
the level of folic acid used in the production of all enriched cereal-
grain products. Providing for a single level, with provision for
reasonable overages within the limits of current good manufacturing
practice (CGMP), has worked well with the other nutrients (thiamin,
niacin, riboflavin, and iron) required to be added to enrich bread,
rolls, and buns and various flour products. The provision for
``reasonable overages'' in the standards for enriched bread, rolls, and
buns (Sec. 136.115(a)(3)) and enriched flour (Sec. 137.165(c)) provides
manufacturers with flexibility to ensure that required levels for the
added nutrients will be met, and that these levels will be maintained
throughout the shelf life of the food under customary conditions of
distribution and storage. While FDA is not establishing a specific
upper limit for folic acid addition, the agency advises that reasonable
variations for overages of folic acid will be assessed on the same
basis as that for the other added nutrients in these foods. Those
reasonable variations are based on a number of factors, including the
technology of nutrient addition, the possibility of nutrient
deterioration, the firms' quality control procedures, and appreciation
by the manufacturer of these factors.
FDA acknowledges that some of the standards for enriched cereal-
grain products that are the subject of this final rule specify the
levels of added nutrient (thiamin, riboflavin, and iron) in terms of
ranges, and FDA has continued this approach with respect to the
addition of folic acid in those products. In addition, the agency notes
that it received a petition (Docket No. 94P-0413/CP 1) subsequent to
the issuance of the folic acid health claims proposal to amend the
standards for enriched macaroni and noodle products to provide for
nutrient addition in terms of a single level with provision for
reasonable overages. However, FDA is not making the change to a single
enrichment level in those standards at this time because, while it has
reached a final decision on folic acid fortification, it has not had an
opportunity to fully analyze the petition. FDA is not aware of any
reason why it should delay action in the present rulemaking while it
analyzes the petition. Thus, until such time as the agency rules on the
petition, the standards in question will continue to provide for
nutrient addition in terms of ranges.
The ranges established in those standards provide a measure of
flexibility in selecting the target level when nutrients are added to
foods that consist of large particles such as farina or rice, or for
preparations (e.g., semolina or other ingredients) used for
manufacturing enriched macaroni or noodle products. The nutrients,
which usually are in the form of a fine powder, have a tendency to
settle out and to make uniform blends with the cereal grains more
difficult to achieve. In such instances, manufacturers, depending on
their application process, may select target levels at the upper end of
the range to ensure that the minimum levels established for the
nutrients will be met. Thus, to enable manufacturers to adhere to
procedures that will deliver the minimum level of nutrients required by
the standards and to compensate for variables in the processing
operations, the agency is continuing to provide for nutrient additions
in terms of ranges for the other enriched foods as set forth below.
FDA also notes that the regulations for nutrition labeling in
Sec. 101.9(g)(4)(i) require that added nutrients be present in the food
at levels that are at least equal to the amount declared on the label.
In addition, Sec. 101.9(g)(6) provides for reasonable overages within
the limits of CGMP. Thus, the manufacturer bears the responsibility of
ensuring that not only will the requirements for added nutrients in the
respective standards of identity be met, but also that the content of
any added nutrient is accurately declared in nutrition labeling.
Therefore, consumers should receive the stated quantity of each added
nutrient whether the standard provides for the added nutrient in terms
of a single level or a range.
a. Enriched flour. No specific comments were received on the
fortification of enriched flour with folic acid. Thus, as proposed, FDA
is requiring that enriched flour contain 0.7 mg/lb of folic acid. FDA
derived this value by adding the fortification level of 0.635 mg/lb to
the Food and Nutrition Board's folate value of unfortified flour of
0.076 mg/lb, which yields 0.711 mg/lb. The agency rounded this value to
0.7 mg/lb. Accordingly, based on this calculation, FDA is amending the
standards of identity for enriched flour (Sec. 137.165) and enriched
self-rising flour (Sec. 137.185), and, by cross-reference, enriched
bromated flour (Sec. 137.160), to require that these foods contain 0.7
mg/lb of folic acid.
b. Enriched bread, rolls, and buns. FDA is amending the standards
of identity for enriched bread, rolls, and buns in Sec. 136.115 to
require that these foods contain 0.43 mg/lb of folic acid. This rate of
fortification is proportionally consistent with the fortification rate
for the B vitamins (thiamin, riboflavin, and niacin) when
[[Page 8790]]
enriched flour is used in making these foods. For example, the levels
of thiamin, riboflavin, and niacin in enriched flour (Sec. 137.165) are
2.9, 1.8, and 24.0 mg/lb, respectively, and in enriched bread
(Sec. 136.115) are 1.8, 1.1, and 15.0 mg/lb, resulting in a ratio of
approximately 1.62 to 1. In the case of the level of folic acid, the
level for enriched flour is 0.7 mg/lb compared to 0.43 mg/lb for bread,
resulting in a ratio 1.63 to 1. The levels of enrichment specified for
the B vitamins and folic acid content are slightly lower in enriched
bread products than in enriched flour to allow the bread products to be
made from the standardized enriched flour without further
fortification.
c. Enriched farina. In the standards of identity proposal, FDA
proposed to establish a fortification level for folic acid in enriched
farina (Sec. 137.305) on the same basis as that for enriched wheat
flour, i.e., 1 lb of the food would contain not less than 0.7 mg of
folic acid.
One comment disagreed with the agency's rationale and argued that
enriched farina is a different product than enriched wheat flour and
therefore should not be fortified at the same level as enriched wheat
flour. The comment asserted that farina is used differently than flour.
For example, according to the comment, farina is often used as an
ingredient in the less expensive pastas to replace the more expensive
semolina. The comment pointed out that farina is also eaten as a hot
cereal, and that precooked breakfast cereals are fortified with folic
acid. The comment did not offer an alternative fortification level or
data on which an alternative level could be based.
Because both wheat flour and farina are made from the endosperm of
wheat, that portion of the wheat kernel that remains after the bran
layer and germ have been removed, and because it is the bran layer and
germ that contain most of the B vitamins, including the naturally
occurring folate, the amount of B vitamins lost during processing would
be similar in both foods. Therefore, the agency finds that it is
reasonable to fortify both flour and farina on the same basic level of
140 g/100 g.
However, FDA acknowledges that enriched farina and enriched flour
may serve different functions. Farina is often used as a substitute for
a flour-containing food, e.g., as a hot cereal at breakfast, with or
without other cereal-grain products being consumed at that meal, and it
may be used in other foods such as pasta. However, the agency finds no
basis to change the fortification level based on these possible end
uses of the products because these uses are governed by other
regulations. For example, when farina is used as an ingredient in the
manufacture of precooked or instant breakfast cereal products, the
level of enrichment is governed by the food additive regulation in
Sec. 172.345. That regulation provides that such ready-to-eat cereals
may be enriched with folic acid up to 100 percent of the daily value
per serving (i.e., 400 g/serving). Neither this final rule nor
the food additive final rule published elsewhere in this issue of the
Federal Register, would affect the continued addition of folic acid to
the precooked or ready-to-eat breakfast cereals that are manufactured
with farina.
With respect to pasta products, the agency notes that the standard
of identity for enriched macaroni and noodle products provides for the
use of farina as an ingredient. However, the agency is not persuaded
that it should adjust the fortification level for farina based on this
possible use of this food. In cases where farina is used as an
ingredient in an enriched macaroni or noodle product, the manufacturer
has the option of adding enrichment nutrients to the farina at the
flour mill or at the manufacturing facility to meet the requirements of
the standard of identity for enriched macaroni or noodle products.
One comment pointed out that farina is not washed before cooking as
had been noted in the proposal, and, thus, washing should not be a
factor in determining appropriate fortification levels.
The agency acknowledges that current farina product labels do not
suggest that enriched farina products need to be rinsed before cooking.
Thus, with current technology, rinsing of the enriched farina product
would not be a factor in deciding on an appropriate value for vitamin
and mineral addition to farina. However, the agency notes that the
proposed upper limit was not based solely on the fact that the product
may be rinsed but also on the fact that it may be diluted when prepared
in other recipes. The comment did not offer data to persuade the agency
to deviate from the proposed upper limit of folic acid addition. Thus,
as proposed, the agency is amending the standard of identity for
enriched farina to provide for an upper limit for folic acid addition
(0.87 mg/lb) that is approximately 25 percent higher than the minimum
of 0.7 mg/lb as it has done for the other B vitamins (thiamin,
riboflavin, and niacin) that are required to be present in enriched
farina.
2. Corn and Rice Products
a. Enriched corn grits. No specific comments were received
regarding the addition of folic acid to enriched corn grits. Thus, as
proposed, FDA is amending Sec. 137.235 to require fortification of
enriched corn grits with the same level of folic acid as that
established for enriched wheat flour products, such that each pound of
the food would contain at least 0.7 mg of folic acid. FDA is also
establishing the proposed upper limit for folic acid fortification of
1.0 mg/lb, which is approximately 50 percent higher than the minimum of
0.7 mg/lb, as it has done for the other B vitamins (thiamin,
riboflavin, and niacin) that are required to be present in enriched
corn grits.
The agency notes that it published a proposed rule in the Federal
Register of October 13, 1995 (60 FR 53480), that would revoke the
standard of identity for enriched corn grits. If comments to the
proposal support revocation of this standard of identity, the
provisions set forth in this final rule for enriched corn grits will
also be revoked. FDA believes, however, that enriched corn grits is a
widely consumed food that is likely to be eaten by women in need of
additional sources of folate. Therefore, should FDA revoke this
standard of identity, the agency is prepared to amend Sec. 172.345, the
food additive regulation on folic acid, to include fortified grits to
the list of nonstandardized foods to which folic acid may be added.
b. Enriched corn meals. No specific comments were received
regarding the enrichment of corn meal products with folic acid. Thus,
as proposed, FDA is amending the standard of identity in Sec. 137.260
to provide for a minimum folic acid level that is consistent with that
established for enriched flour, such that each pound of the food
contains 0.7 mg. Because corn meal products may be used as substitutes
for wheat flour products, the agency believes, as discussed in the
standards of identity proposal (58 FR 53305 at 53308), that consumers
expect to be able to obtain the same levels of nutrients from enriched
corn meals as from enriched wheat flour. FDA is also establishing an
upper limit for folic acid addition (i.e., 1.0 mg/lb which is
approximately 50 percent higher than the minimum fortification level),
as has been done for the added B vitamins. The upper limit on the other
B vitamins is intended to prohibit addition of excessive amounts of the
nutrient and to ensure uniformity in composition of corn meals. FDA
finds that, for the same reasons, an upper
[[Page 8791]]
limit on the addition of folic acid of 1.0 mg/lb is necessary.
c. Enriched rice. The folic acid content of rice varies from 0.008
mg/100 g (0.036 mg/lb) for white rice to 0.020 mg/100 g (0.090 mg/lb)
for brown rice (Ref. 7). FDA proposed to amend the standard of identity
for enriched rice to provide for the addition of not less than 0.7 mg
and not more than 1.4 mg of folic acid per pound (58 FR 53305 at
53312). The agency also noted in the standards of identity proposal
that rice in the United States may be enriched by addition of a powder
mixture containing the added nutrients or by use of a rice premix
consisting of rice kernels coated with a concentrated nutrient mix.
When the powder enrichment procedure is used, the label of the package
generally bears a statement that the rice should not be rinsed before
or drained after cooking, in accordance with Sec. 137.350(c), to ensure
that the rice retains the added nutrients. However, the agency stated,
there is no assurance that these instructions are being followed. In
the case of the rice premix, a special coating is applied to the rice
kernels, so that the added nutrients will not be washed off if the
product is rinsed before cooking. Rice coated with the premix is
blended with unenriched rice such that the finished enriched rice
product will contain the required minimum levels of added nutrients.
The agency stated that the proposed range would provide flexibility in
the production of the enriched rice and ensure that the food, when
prepared for consumption, will contain the required minimum levels of
nutrients.
16. According to comments on the standards of identity proposal,
most enriched rice produced in this country is manufactured using the
powder procedure to add nutrients. A comment stated that some rice
processors are very concerned about the addition of an enrichment
powder mix containing folic acid because folic acid could result in off
colors, taste, and aromas in the enriched rice. The comment maintained
that firms fear that consumers may reject the enriched rice product if
it does not possess the usual white color. It further stated that
processors needed additional time to conduct research on the addition
of folic acid to rice.
While FDA acknowledges that the provision in the enriched rice
standard for the addition of riboflavin has been stayed because of
objections from the industry stating that riboflavin addition results
in a yellow discoloration being imparted to the rice that is
unacceptable to consumers (23 FR 1170, February 25, 1958), the agency
has not received any information from rice processors that demonstrates
that addition of folic acid to rice will result in off colors, taste,
or aromas in the enriched rice product. Thus, as proposed, the agency
is amending the standard of identity for enriched rice (Sec. 137.350)
to include a range for the folic acid fortification level, 0.7 mg/lb to
1.4 mg/lb, with the lower limit being consistent with the folic acid
fortification level for enriched wheat flour. FDA concludes that use of
the same minimum level of fortification is appropriate because it is
consistent with the Food and Nutrition Board's recommendation that the
same restoration level be used for wheat flour, corn products, and rice
(although the Food and Nutrition Board only recommended addition at
restoration levels). FDA is also establishing an upper limit for folic
acid fortification of enriched rice of 1.4 mg/lb, as it has done with
other enrichment nutrients added to rice. As discussed in the standards
of identity proposal (58 FR 53305 at 53309), the upper level is based
on the way that rice is fortified in this country.
The agency recognizes that manufacturers will need time to
experiment with the addition of folic acid to their products. FDA is
providing approximately 2 years from the publication date of this final
rule to allow manufacturers to test their ability to comply with the
new requirements and to make appropriate label changes.
17. One comment stated that, because the powder-enriched rice
suffers substantial nutrient loss when it is washed (as rice is by many
consumers), it is unlikely that folate intakes will increase as much as
FDA estimates. The comment suggested that the agency should,
consequently, increase the fortification level.
FDA disagrees with the comment. For those consumers who wish to
consume ``enriched'' rice, the agency has provided requirements in the
standard of identity for enriched rice to ensure delivery of the
required nutrients. Section 137.350(c) requires that enrichment
nutrients be present in the rice in such form and at such levels that
if the enriched rice is washed, it contains not less than 85 percent of
the minimum quantities of the nutrients required to be present in the
enriched rice. If they are not present in such form or at such levels
to comply with these minimum requirements, the label of the enriched
rice must bear the statement ``to retain vitamins do not rinse before
or drain after cooking'' immediately following the name of the food. In
addition, the label cannot bear cooking directions that call for
washing or draining the enriched rice. In the case of precooked
enriched rice, the package must be labeled with directions for
preparation that, if followed, will avoid washing away or draining off
enrichment ingredients.
As discussed above, FDA is providing for addition of folic acid at
the level of 140 g/100 g of the enriched cereal-grain
products. The agency has concluded that this fortification level is
necessary to help ensure that the total consumption level will not
exceed the recommended daily consumption level of 1 mg (or 1,000
g). To minimize the potential losses in enrichment nutrients
in rice, the agency had provided for a range in the levels, with an
upper limit that is twice that of the minimum level required to be
present in the rice. Thus, rice processors who use the powder-
enrichment procedure, where nutrient losses would be expected to be
greater, will be able to use a level of enrichment nutrients that makes
it likely that consumers will receive the minimum levels of nutrients
required to be in the food.
3. Macaroni and Noodle Products
The standards of identity for enriched macaroni products
(Sec. 139.115), enriched nonfat milk macaroni products (Sec. 139.122),
and enriched noodle products (Sec. 139.155), and the cross- referenced
standards of identity for enriched vegetable macaroni products
(Sec. 139.135) and enriched vegetable noodle products (Sec. 139.165),
provide for significantly higher levels of nutrient addition than the
related flour standards of identity because these products are usually
cooked in a large amount of water that is usually discarded after
cooking and before consumption of the macaroni and noodle products.
18. One comment asserted that because of the preparation process
for macaroni and noodle products, vitamin retention data are absolutely
essential before any level of enrichment can be discussed. Thus, the
comment recommended that FDA delay implementation of folic acid
fortification of cereal-grain products until more concrete information
is available on vitamin retention with cooking.
FDA is not delaying the implementation of folic acid fortification,
as suggested by the comment, because of the need to increase the folic
acid levels in the diets of women of childbearing age. The agency
recognizes that there will be losses in the content of water soluble
vitamins when the enriched macaroni and enriched noodle products are
cooked in water, and that water is drained from the foods before
consumption (Ref. 8). The agency also
[[Page 8792]]
acknowledges that data on retention of the vitamins (thiamin, niacin,
and riboflavin) required to be added to enrich these foods are limited,
and that it is difficult to make inferences as to the retention of
added folic acid when folic acid enriched products are cooked in water,
and the water is discarded. However, there are some data to suggest
that the retention rates are similar.
According to a study conducted by Ranhortra, et al. (Ref. 8), on
the retention rates of the thiamin, niacin, and riboflavin in three
enriched pasta products (spaghetti, noodles, and macaroni), at least 50
percent (75 to 77 percent on average) of the added nutrients was
retained after cooking in water and draining. This study looked at the
retention of the naturally occurring folate in the pasta products,
before and after cooking, and found that the retention rate was 77 to
79 percent. Based on this data, FDA does not expect that the retention
rate of folic acid in these products would be significantly different
from the retention rates of the other B vitamins.
FDA recognizes that, as with other grain products, manufacturers
will need to conduct research on the most effective means of adding
folic acid and of ensuring that the added folic acid will be available
in the finished food. Such studies will need to focus on not only the
method of adding the nutrient but also on the stability of the vitamin
during usual conditions of distribution and storage. The agency notes
that similar studies were required when FDA established requirements
for the addition of the other B vitamins to enriched cereal-grain
products. In addition to studies, it may be necessary for manufacturers
to develop label instructions on how the product should be prepared,
e.g., instructions on limiting the amount of water to be used in its
preparation or cooking time, and on whether the cooked food can be
rinsed without loss of nutrients before serving, to ensure maximum
retention of folic acid and the added water soluble nutrients.
FDA is requiring the addition of folic acid to macaroni and noodle
products in the same proportion as it is requiring such addition to
enriched flour, except that the required level (expressed in terms of a
range) will be approximately 25 percent higher for macaroni and noodle
products than the required level of folic acid that is to be added to
flour. This 25-percent increment is consistent with the requirements
for the other added nutrients (thiamin, riboflavin, niacin, and iron)
in the enriched macaroni and noodle products standards, compared to
those in the standards of identity for flour products.
Accordingly, as proposed, FDA is requiring that the enriched
macaroni and noodle products contain from 0.9 to 1.2 mg/lb of folic
acid.
G. Effective Date
19. Many comments expressed concern over the statement in the
standards of identity proposal that the final rule would become
effective 1 year after publication. The comments stated that it would
be difficult and impractical to synchronize the addition to a food of a
folic acid-fortified enriched cereal- grain product with the
availability of revised labels for that food that declare folic acid in
the ingredient statement. These comments pointed out that enrichment
nutrients are generally not added to each separately labeled product
but are added to thousands of pounds of flour at the flour mill, the
flour is sold to other manufacturers as an ingredient, and then this
ingredient is used in many different products. Thus, the comments
asserted that as a matter of economic necessity, the enrichment of all
these products occurs at the same time, regardless of the availability
of new labeling. One comment recommended that FDA establish an
effective date of at least 2 years from the date of publication of the
final rule. The comment asserted that a 2-year period would allow
adequate time to incorporate changes on labels of slower moving
products as well as products with higher retail turn rates. Thus, the
comment continued, existing packaging inventory could be used, thereby
reducing the cost impact of the regulation. Another comment suggested a
``phase-in'' period of at least 3 years or, in the alternative, an
effective date consistent with the next uniform effective date,
whichever is later. In support of the suggestion, the comment asserted
that a ``phase-in'' period would allow label changes to take place
concurrent with the folic acid addition on a product-by-product basis.
In addition, the comment contended, such action would allow
manufacturers to exhaust their current label inventory and reduce the
economic impact of the regulation. Moreover, the comment continued,
additional time is needed for analytical testing for declaration of
folic acid in nutrition labeling.
FDA acknowledges the concerns raised in these comments regarding
label changes that must accompany the addition of folic acid to
enriched cereal-grain products and to foods in which these products are
used as ingredients. FDA is persuaded by the concerns raised in the
comments to establish an effective date that will provide manufacturers
with time to implement the label and formulation changes required by
the amendments established in this final rule. The agency agrees with
the comment that suggested that FDA establish an effective date of at
least 2 years from the date of publication of the final rule. A 2-year
period would allow manufacturers time to exhaust current packaging
inventory, add folic acid to their statement of ingredients and the
nutrition facts panel as other changes are made to update package
labeling, and subsequently ensure that packaging is available that
accurately reflects the addition of folic acid to their products.
Furthermore, the agency points out that a 2-year period is consistent
with the amount of time given for implementation of the Nutrition
Labeling and Education Act (NLEA) requirements. Thus, the effective
date of this final rule will be January 1, 1998. The agency notes,
however, that compliance with the requirements established in this
final rule may begin immediately, provided that the label accurately
reflects that folic acid has been added to the product. Furthermore,
the agency will not object to the use of stickers to bring a product
label into compliance with the ingredient labeling and nutrition
labeling provisions. The agency notes, however, that unless the
standardized food bears a claim about folate, the declaration of folate
in the nutrition label is voluntary.
20. A few comments that raised concern about label changes that
must accompany the addition of folic acid suggested that the agency
permit folic acid to be added to the product without requiring
declaration in the ingredient statement. One comment contended that
there was no safety issue regarding folic acid that would require its
declaration on the label.
Traditionally, the agency has not permitted manufacturers who
change their formulas by adding or deleting ingredients to use
noncompliant labels. Furthermore, as discussed in response to the
previous comment, the agency is establishing an effective date in this
final rule that will provide industry ample time to ensure that
products enriched with folic acid are labeled in compliance with the
regulations.
In response to the argument that the addition of folic acid need
not be declared because it does not raise a safety issue, the agency
advises that the act requires that all foods fabricated from two or
more ingredients declare each of its ingredients by common or usual
name in a list of ingredients. This
[[Page 8793]]
requirement applies without regard to whether there is a safety issue
regarding the food. Consequently, the agency has not been persuaded by
the comments to permit the addition of folic acid to foods without also
requiring that folic acid be declared in ingredient labeling.
III. Economic Impact
FDA has examined the impacts of this final rule to require the
addition of folic acid to enriched cereal-grain products that conform
to a standard of identity as required by Executive Order 12866 and the
Regulatory Flexibility Act. Executive Order 12866 directs agencies to
assess all costs and benefits of available regulatory alternatives and,
when regulation is necessary, to select regulatory approaches that
maximize net benefits (including potential economic, environmental,
public health and safety, and other advantages; distributive impacts;
and equity). The Regulatory Flexibility Act (Pub. L. 96-654) requires
the analysis of options for regulatory relief for small businesses. FDA
finds that this final rule is not a significant regulatory action as
defined by Executive Order 12866. In compliance with the Regulatory
Flexibility Act, the agency certifies that this final rule will not
have a significant impact on a substantial number of small businesses.
On October 14, 1993 (58 FR 53305 at 53309), FDA published an
economic impact analysis of the proposed requirements under the
previous Executive Order (E.O. 12291). In the analysis, the agency
evaluated the following regulatory options:
1. Improve dietary practices among women of childbearing age.
2. Require fortification with folic acid at 140 g/100 g.
3. Require fortification with folic acid at: (a) A lower level,
specifically 70 g/100 g; or (b) a higher level, specifically
350 g/100 g.
In response to the standards of identity proposal, the agency
received several comments that provided information that has altered
its economic impact analysis. Costs and benefits for each of the
regulatory options are examined below.
A. Costs
Cost estimates are revised first for fortification at 140 g/
100 g followed by the cost estimates for fortification at 70
g/100 g and 350 g/100 g.
1. Require Fortification With Folic Acid at 140 g/100 g
Costs of fortifying with folic acid at 140 g/100 g include
health costs and reformulation costs.
a. Health costs. Potential health costs of this regulatory option
include the costs of neurologic disease associated with masking of the
anemia of vitamin B12 deficiency. Several studies have found that
folic acid can mask the anemia of vitamin B12 deficiency at levels
as low as 250 g/day. Although there is no scientific consensus
on the percentage of diagnoses of vitamin B12 deficiency anemia
that would be complicated by folate intake at this level, the agency
has determined that adverse health effects are not significant until
folate intake reaches 1 mg/day. In the proposal, FDA tentatively
concluded that the 140 g/100 g level for fortification of
enriched cereal grain products was the most appropriate level based on
a regulation that would have required that fortification of all
breakfast cereals be limited to 100 g folic acid/serving. This
limitation was proposed under a separate food additive regulation
published elsewhere in the same Federal Register (58 FR 53312). With
this option, 140 g/100 g, FDA preliminarily concluded that
intake of persons in the target and nontarget populations would remain
below 1 mg/day.
Comments submitted in response to the proposal to limit breakfast
cereals to 100 g folic acid/serving persuaded the agency to
allow breakfast cereals to continue to contain up to 400 g
folic acid/serving. If all breakfast cereals were fortified at the
level of 400 g/serving, some high end consumers could consume
more than 1 mg folate/day. However, most cereals currently are
fortified at a level of 100 g/serving (25 percent of the
reference daily intake (RDI)) and only an estimated 5 percent of
breakfast cereals fortify at a level of 400 g (100 percent of
the RDI).
Further, it is unlikely that manufacturers of breakfast cereals
will increase the folic acid level in cereals from 100 g/
serving to 400 g/serving. Since most breakfast cereals that
contain at least 40 g/serving (10 percent of the RDI) of folic
acid can now make health claims (if all other criteria are met),
manufacturers have no incentive to reformulate from 100 g to
400 g per serving and incur reformulation costs.
There are a number of confounding uncertainties that make it
difficult to estimate the potential health costs of folic acid
fortification of enriched grain products (Ref. 9). These include:
1. Current intakes estimated from food consumption survey data may
underestimate actual intakes due to underreporting of food intake;
2. The folate content of foods may be underestimated due to
methodologic difficulties;
3. Good data on the distribution of dietary supplement intake are
not available;
4. Estimates of masking of anemia (with subsequent progression of
neurologic symptoms) based on enumerating only those associated with
pernicious anemia would underestimate potential adverse effects because
all vitamin B12 deficiencies may lead to neurologic problems; and
5. It is difficult to predict effects of changes in dietary
patterns that occur simultaneously with, but independently of, this
regulation. Such changes may be the result of educational efforts by
various organizations, physicians, and health care providers or in
response to health claims.
The last factor is particularly problematic. Recent surveys have
shown a growing awareness of the value of increased folate intake among
both the population as a whole and, specifically, among women of
childbearing age. From 1994 to 1995, awareness of the problems
associated with insufficient folic acid intake grew from 28 to 44
percent among women of all ages (Ref. 10). As awareness grows, it is
likely that folic acid intake will increase in the target group. In
addition, new label claims allowed by the final rule for health claims
on the association between folate intake and a reduced risk of NTD's
are also expected to increase folic acid intake among women of
childbearing age. However, the survey mentioned above also showed that
such awareness is strongly positively correlated with education, so
that these messages may not reach less well- educated women in the
population.
In the folic acid health claims proposal, FDA tentatively found
that there were several nontarget groups whose intake levels of folate
may approach 1 mg/day (intakes > 800 g/day) with a level of
140 g/day and use of dietary supplements. These include
individuals in groups including children 4 through 10 years of age and
males 11 through 18, 19 through 50, and 51+ years of age. Individuals
at risk of pernicious anemia include both males and females over 51 and
Hispanic females ages 40 and above. The largest group at potential risk
includes males over 51 who take dietary supplements. In order to be at
risk of potential adverse effects from consuming greater than 1 mg
folate/day individuals must: (1) Consume an excessive amount of folic
acid through some combination of supplements containing folic acid and
consumption of fortified enriched grain products and other products
containing folic acid; and (2) have low vitamin B12 status or have
vitamin B12 deficiency.
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Because of the difficulties mentioned above, it is not possible to
estimate the number of people in the high risk subgroup who fit all of
these categories.
However, one such attempt has been made between the time of the
standards of identity proposal and this final rule. In this analysis,
Romano et. al. made the following assumptions:
1. The annual incidence of pernicious anemia is 9.5 to 16.7 per
100,000 persons (based on two European population-based studies);
2. With low level fortification, 5 to 10 percent of these patients
would receive enough folic acid to mask the anemia of vitamin B12
deficiency; and
3. Between ``24 and 26 percent of patients with pernicious anemias
whose anemias respond to folic acid develop neurologic signs'' (Ref.
11).
Based on these assumptions, the authors estimated that
approximately 500 people per year would develop neurologic disease as a
result of low level folic acid fortification. Other authors contend
that this estimate may considerably understate the number of cases
(Ref. 12). On the other hand, one uncertainty not acknowledged by this
analysis is that this rule may create a market for cereal-grain
products that are not ``enriched.'' A nonstandardized cereal-grain
product could be produced that was not labeled as being enriched with
folate (although it could have other vitamins and minerals added and be
labeled to reflect this fact) and could be marketed to people at risk
of vitamin B12 deficiency. If such a market developed, and at-risk
persons were encouraged to consume products not enriched with folic
acid, this problem might be reduced. In addition, sale to high risk
subgroups of nonstandardized products such as whole wheat breads
(mentioned earlier in this preamble) which do not need to be enriched,
may increase as a result of this rule.
Another uncertainty that would reduce the number of cases of masked
anemia, mentioned by one comment, is the percentage of cases of
B12 deficiency that could be discovered with routine population
screening. If such tests were performed proactively, B12
deficiencies might be identified before neurologic symptoms developed.
In addition, it is not clear whether the European population-based
studies that reported the annual incidence of diagnosed pernicious
anemia are relevant to the U.S. population. Some population groups in
the United States (e.g., African-American women) appear to experience
an earlier age-at-onset of pernicious anemia than occurs with
pernicious anemia in Northern European countries, which are
predominantly Caucasian populations.
Although not able to estimate an absolute number, FDA has
calculated a cost per case of neurologic symptoms resulting from
masking of the anemia of pernicious anemia so that a break-even point
may be calculated at which point benefits would equal the costs. The
cost-per-illness will be calculated using the sum of medical costs and
the cost of lost utility. The majority of medical costs, which include
costs for physicians, other hospital services, and drugs, are normally
paid by insurance such that estimates based on willingness-to-pay to
avoid death would not be likely to be included. Other utility losses,
including death, pain and suffering, immobility, and lost productivity
associated with morbidity, are calculated as a function of the
willingness- to-pay (WTP) to avoid death. Thus, for example, each day
of morbidity is a day spent in less than perfect health engendering
some utility loss. That is, each day of illnesses is somewhere between
a day of full utility, 1, and death, 0. Because WTP to avoid death does
not include the medical expenditures mentioned above, these costs are
calculated separately.
The expected utility loss estimates were calculated in the
preliminary economic impact analysis (the PRIA) in the standards of
identity proposal. The most common symptoms of a delay in the diagnosis
of vitamin B12 deficiency are permanent paresthesia (numbness or
tingling) in the hands or feet and ataxia (inability to coordinate
voluntary muscular movements).
In the standards of identity proposal, FDA estimated the cost per
case to be approximately $538,000 (Ref. 13). This estimate was
calculated using weighted probabilities of a mild (95 percent) and a
severe case (5 percent) and the value of expected utility loss per case
of neurologic disability. For each state, mild and severe, a health
status value was calculated that related the state to a day of
``perfect health''. Thus, a person with a mild case of neurologic
disability is calculated to enjoy only 70 percent of the utility per
day as that of a person in a perfectly healthy state. For a more severe
case it would be approximately 50 percent (Ref. 14). Using the likely
duration of each illness, the utility loss from a severe neurologic
disability was found to be equivalent to a loss of 5.56 perfect-health
years. From the value of a perfect health year, $138,889 (Ref. 14), the
value of expected utility loss per case of mild neurologic disability
was estimated to be $525,598. The utility loss due to severe neurologic
disability was estimated in a similar fashion to be $772,598 per case.
The weighted value (based on likelihood of a mild versus severe case)
of a case of masked pernicious anemia leading to permanent adverse
health effects was calculated as the weighted mean: (0.95 x 525,598)
+ (0.05 x 772,598) = $537,948.
In addition to utility costs, hospital costs of neurologic effects
due to pernicious anemia have been estimated by Romano et al. (Ref.
11). In this study, each neurologic case requires hospitalization once
for an average duration of 16 days at $867/day. After factoring in
physician services and other direct and indirect costs, the total
direct outlay cost of neurologic disease as a result of folic acid
fortification was estimated to be $33,000 per case (Ref. 11). Total
costs per case are thus calculated to be $570,000.
However, as mentioned in Romano et al., the cost estimate may be
too high because these estimates assume that all neurologic disease
would be severe, and mild cases may not require hospitalization (Ref.
11). In addition, this estimate may be too high if there were routine
population wide screening for vitamin B12 deficiency, although
this is not currently occurring nor is it likely to be instituted. At
the same time, however, the estimate may be too low if a case leads to
later complications or to the need for lifelong skilled nursing care
(Ref. 11).
These costs, lost utility and hospital costs, are not annual costs.
Once someone has experienced permanent adverse health effects from
masked pernicious anemia, that person ought not to be included in the
costs estimated for subsequent years, since the discounted value of
their permanent adverse health effects has already been calculated and
attributed to the first year. Any costs in subsequent years would
involve only those entering the at-risk age pool.
b. Other health costs. FDA is aware of the potential for other
health problems resulting from increased long-term intakes of folic
acid but has no data with which to quantify these costs.
c. Reformulation costs. Reformulation costs associated with this
option were estimated in the proposal to be $27 million for the first
year. The cost of adding the required folic acid is approximately $4
million per year. The cost of testing was estimated to be about $2.5
million per year and the cost of the required label changes $20
million. FDA will use these costs for this final rule as no comments
were received on this part of the analysis.
In addition, some countries, such as Canada, do not allow folic
acid fortification of these products. Thus, this option would require
that separate
[[Page 8795]]
production runs be made for fortified products exported, to and
imported from, these countries. This requirement may preclude some
manufacturers from the export market. None of the comments provided
information that would assist in determining the costs of having
different international requirements.
2. Costs of Requiring Fortification With Folic Acid at Either 70
g/100 g or 350 g/100 g
The total cost of the option to fortify at 70 g/100 g in
the first year was estimated in the proposal to be $25 million plus the
cost of separate production runs for these products exported to and
imported from certain foreign countries. For the option of fortifying
with folic acid at 350 g/100 g, the PRIA estimated a cost of
$1.88 billion annually.
With the latter option, the folate intake of some consumers at risk
of vitamin B12 deficiency (including pernicious anemia) would be
raised to levels exceeding 1 mg per day. One comment to the proposal
said that the estimated health costs of fortifying at this (higher)
level were unrealistically high as FDA had failed to take into account
that each subsequent year should only account for new cases (Ref. 11).
Because of the problems with estimating numbers of people who will
become ill at either level, FDA will not quantify these costs.
Reformulation costs. In the proposal, the cost of the folic acid
required to fortify at 350 g/100 g was estimated to be
approximately $10 million per year. The cost of testing was estimated
to be $2.5 million and the cost of the required label changes was
estimated to be $20 million.
B. Benefits
1. Require Fortification with Folic Acid at 140 g/100 g
The primary benefit of this option is a reduction in the number of
infants born with NTD's each year. In addition, a possible benefit will
be a reduction in cardiovascular diseases from intake of increased
folate. However, there is still tremendous uncertainty with respect to
the latter effect (for a more complete discussion, see folic acid food
additive document published elsewhere in this Federal Register).
Based on a synthesis of information from several studies, including
those which used multivitamins containing folic acid at a daily dose
level of 0.4 mg, it was inferred that folic acid alone at
levels of 0.4 mg per day will reduce the risk of NTD's. This conclusion
was based on two studies, one from a high risk population (Hungary)
with a small number of subjects that was found to be 100 percent
effective and another from a study that showed zero risk reduction in a
low prevalence population (California and Illinois). From these
studies, the PHS estimated a reduction of 50 percent of the number of
NTD's in the United States. Other studies evaluated by PHS varied in
their results. A possible explanation for the lack of effectiveness was
that studies were conducted in populations with a low prevalence of
NTD's which may not have had a folate-related subset of NTD's.
In a study by Shaw et al., the reduction in NTD risk associated
with folate intake is consistent with other studies, but the reduced
risk was found to be specific to particular subsets of the population,
primarily non-Hispanic women and women whose education did not exceed
high school (Ref. 15). For Hispanic women, the risk reduction was
approximately 10 percent. In a study by Romano et. al., the 50 percent
estimate of reduced risk of NTD's was used with literature-based
sensitivity limits of 67 percent (Ref. 16) and 20 percent (Refs. 11 and
17).
In the proposal, FDA estimated that under the 140 g/100 g
option, 116 NTD's per year would be prevented (50 percent reduction).
Initiation of this option was also estimated to prevent an additional
25 infant deaths each year. Total benefits of this option were
estimated to be between $651 and $788 million per year.
There is no consensus on the dose-response relationship between
folate intake and the reduction in risk of NTD's. However, using a
lower bound of 10 percent and an upper bound of a 50 percent reduction
in NTD's, the estimated reductions in total cases would be between 25
(5 deaths) and 125 (27 deaths) resulting in quantified benefits ranging
from $220 to $700 million.
2. Require Fortification with Folic Acid at 70 g/100 g and 350
g/100 g
a. 70 g/100 g. The benefit of requiring fortification of
these products at 70 g/100 g was estimated in the proposal to
be between $326 and $394 million. Using the sensitivity limits
mentioned above, 10 to 50 percent of the estimated benefits would range
from $110 to $346 million.
b. 350 g/100 g. The benefit of requiring fortification of
these products at 350 g/100 g is estimated to be between $550
million and $1.4 billion. This option is the only option that would
generate significant health costs.
C. Conclusion
In accordance with Executive Order 12866, the agency has analyzed
the economic effects of this final rule and has determined that this
rule, if issued, will not be an economically significant rule as
defined by that order.
The cost of this final rule in the first year is estimated to be
approximately $27 million which includes the cost of relabeling,
testing, and fortification. In addition, there may be some health costs
associated with neurologic symptoms resulting from masking the anemia
of vitamin B12 deficiency as well as the cost of separate
production runs for products exported to and imported from certain
foreign countries. The cost of the proposed action in each year after
the first year should be approximately 25 percent of the first year
cost. The benefits are estimated to be between $220 and $700 million
per year. Using a value of $570,000 per case of masked pernicious
anemia resulting in neurologic damage, the break-even number of these
cases at which costs would equal benefits would fall between 386 and
1,228.
Although reformulation costs of this option are approximately $27
million, the cost per firm is expected to be very small. Therefore, in
accordance with the Regulatory Flexibility Act, FDA has determined that
this rule will not have an adverse impact on a substantial number of
small businesses.
IV. Environmental Impact
The agency has carefully considered the potential environmental
effects of this action. FDA has concluded that the action will not have
a significant impact on the human environment, and that an
environmental impact statement is not required. The agency's finding of
no significant impact and the evidence supporting that finding,
contained in an environmental assessment, may be seen in the Dockets
Management Branch (address above) between 9 a.m. and 4 p.m., Monday
through Friday.
V. 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. Centers for Disease Control and Prevention, ``Recommendations
for the Use of Folic Acid to Reduce the Number of Cases of Spina
Bifida and Other Neural Tube Defects,'' in Morbidity and Mortality
Weekly Reports, 41, 1-7, 1992.
2. USDA, Nationwide Food Consumption Survey/Individual Intake-
1987-1988, accession no. PB90-504044, National
[[Page 8796]]
Technical Information Service, Springfield, VA, 1990.
3. Food and Nutrition Board, National Research Council, National
Academy of Sciences, Proposed Fortification Policy for Cereal-Grain
Products, Washington, DC, 36 pp., 1974.
4. Nationwide Food Consumption Survey, Continuing Survey of Food
Intakes by Individuals: Women 19-50 Years Old and Their Children 1-5
years, 1 day, 1985; United States Department of Agriculture,
Hyattsville, MD; NFCS, CSFII, Report No. 85-1, 1985.
5. Subcommittee on Food Technology, Committee on Food
Protection, Food and Nutrition Board, National Research Council,
National Academy of Sciences, Proceedings of a Workshop on
Technology of Fortification of Cereal-Grain Products, Washington,
DC, May 16-17, 1977.
6. USDA Handbook 8-20: Composition of Foods, Cereal Grains, and
Pasta, Raw Processed, Prepared. Rev., October 1989.
7. Hoffpauer, D.W., ``Rice Enrichment for Today,'' Cereal Foods
World, vol. 37, No. 10, pp. 757-759, 1992.
8. Ranhortra, G.S., J.A. Gelroth, F.A. Novak, and R.H. Matthews,
``Retention of Selected B Vitamins in Cooked Pasta Products,''
Cereal Chemistry, vol. 60, No. 6, pp. 476-477, 1985.
9. Crane, N. et al., ``Evaluating Food Fortification Options:
General Principles Revisited with Folic Acid,'' American Journal of
Public Health, vol. 85, No. 5, pp. 660- 666, 1995.
10. FDA, Health and Diet Survey, 1994 and 1995.
11. Romano, P.S. et al., ``Folic Acid Fortification of Grain: An
Economic Analysis,'' American Journal of Public Health, vol. 85, No.
5, pp. 667-676, 1995.
12. Perez-Escamilla, R., ``Folic Acid Fortification for the
Prevention of Neural Tube Defects: Consensus Needed on Potential
Adverse Effects,'' American Journal of Public Health, vol. 85, No.
11, pp. 1587-1588, 1995.
13. Healton, E.B., D.G. Savage, J.C. Brust, T.J. Garett, J.
Lindenbaum, ``Neurologic Aspects of Cobalamin Deficiency,''
Medicine, vol. 7, No. 4, pp. 229-245, 1991.
14. Research Triangle Institute, ``Quality of Well-Being Scale
in Estimating the Value of Consumers' Loss from Food Violating the
FD&C Act,'' vol. II, Final Report, 1988.
15. Shaw, G.M. et al., ``Periconceptional Vitamin Use, Dietary
Folate and the Occurrence of Neural Tube Defects,'' Epidemiology
Resources Inc., 1995.
16. MRC Vitamin Study Research Group, ``Prevention of Neural
Tube Birth Defects: Results of the Medical Research Council Vitamin
Study,'' Lancet, vol. 338, pp. 131- 137, 1991.
17. Mills, J.L., G.G. Rhoads, J.L. Simpson, G.C. Cunningham,
M.R. Conley, M.R. Lassman, M.E. Walden, D.R. Depp, H.J. Hoffman,
``The Absence of a Relation Between the Periconceptional Use of
Vitamins and Neural-tube Defects,'' New England Journal of Medicine,
321:430-435, 1989.
List of Subjects
21 CFR Part 136
Bakery products, Food grades and standards.
21 CFR Part 137
Cereals (food), Food grades and standards.
21 CFR Part 139
Food grades and standards.
Therefore, under the Federal Food, Drug, and Cosmetic Act and under
authority delegated to the Commissioner of Food and Drugs and
redelegated to the Director, Center for Food Safety and Applied
Nutrition, 21 CFR parts 136, 137, and 139 are amended as follows:
PART 136--BAKERY PRODUCTS
1. The authority citation for 21 CFR part 136 continues to read as
follows:
Authority: Secs. 201, 401, 403, 409, 701, 721 of the Federal
Food, Drug, and Cosmetic Act (21 U.S.C. 321, 341, 343, 348, 371,
379e).
2. Section 136.115 is amended by revising paragraph (a)(1) to read
as follows:
Sec. 136.115 Enriched bread, rolls, and buns.
(a) * * *
(1) Each such food contains in each pound 1.8 milligrams of
thiamin, 1.1 milligrams of riboflavin, 15 milligrams of niacin, 0.43
milligrams of folic acid, and 12.5 milligrams of iron.
* * * * *
PART 137--CEREAL FLOURS AND RELATED PRODUCTS
3. The authority citation for 21 CFR part 137 continues to read as
follows:
Authority: Secs. 201, 401, 403, 409, 701, 721 of the Federal
Food, Drug, and Cosmetic Act (21 U.S.C. 321, 341, 343, 348, 371,
379e).
4. Section 137.165 is amended by revising paragraph (a) to read as
follows:
Sec. 137.165 Enriched flour.
* * * * *
(a) It contains in each pound 2.9 milligrams of thiamin, 1.8
milligrams of riboflavin, 24 milligrams of niacin, 0.7 milligrams of
folic acid, and 20 milligrams of iron.
* * * * *
5. Section 137.185 is amended by revising paragraph (a) to read as
follows:
Sec. 137.185 Enriched self-rising flour.
* * * * *
(a) It contains in each pound 2.9 milligrams of thiamin, 1.8
milligrams of riboflavin, 24 milligrams of niacin, 0.7 milligrams of
folic acid, and 20 milligrams of iron.
* * * * *
6. Section 137.235 is amended by revising paragraph (a)(1) to read
as follows:
Sec. 137.235 Enriched corn grits.
(a) * * *
(1) It contains in each pound not less than 2.0 milligrams (mg) and
not more than 3.0 mg of thiamin, not less than 1.2 mg and not more than
1.8 mg of riboflavin, not less than 16 mg and not more than 24 mg of
niacin or niacinamide, not less than 0.7 mg and not more than 1.0 mg of
folic acid, and not less than 13 mg and not more than 26 mg of iron
(Fe);
* * * * *
7. Section 137.260 is amended by revising paragraph (a)(1) to read
as follows:
Sec. 137.260 Enriched corn meals.
(a) * * *
(1) It contains in each pound not less than 2.0 milligrams (mg) and
not more than 3.0 mg of thiamin, not less than 1.2 mg and not more than
1.8 mg of riboflavin, not less than 16 mg and not more than 24 mg of
niacin or niacinamide, not less than 0.7 mg and not more than 1.0 mg of
folic acid, and not less than 13 mg and not more than 26 mg of iron
(Fe);
* * * * *
8. Section 137.305 is amended by revising paragraph (a)(1) to read
as follows:
Sec. 137.305 Enriched farina.
(a) * * *
(1) It contains in each pound not less than 2.0 milligrams (mg) and
not more than 2.5 mg of thiamin, not less than 1.2 mg and not more than
1.5 mg of riboflavin, not less than 16.0 mg and not more than 20.0 mg
of niacin or niacinamide, not less than 0.7 mg and not more than 0.87
mg of folic acid, and not less than 13.0 mg of iron (Fe).
* * * * *
9. Section 137.350 is amended by revising paragraph (a)(1) to read
as follows:
Sec. 137.350 Enriched rice.
(a) * * *
(1) Not less than 2.0 milligrams (mg) and not more than 4.0 mg of
thiamin, not less than 1.2 mg and not more than 2.4 mg of riboflavin,
not less than 16 mg and not more than 32 mg of niacin or niacinamide,
not less than 0.7 mg and not more than 1.4 mg of folic acid, and not
less than 13 mg and not more than 26 mg of iron (Fe).
* * * * *
[[Page 8797]]
PART 139--MACARONI AND NOODLE PRODUCTS
10. The authority citation for 21 CFR part 139 continues to read as
follows:
Authority: Secs. 201, 401, 403, 409, 701, 721 of the Federal
Food, Drug, and Cosmetic Act (21 U.S.C. 321, 341, 343, 348, 371,
379e).
11. Section 139.115 is amended by revising paragraph (a)(1) to read
as follows:
Sec. 139.115 Enriched macaroni products.
(a) * * *
(1) Each such food contains in each pound not less than 4.0
milligrams (mg) and not more than 5.0 mg of thiamin, not less than 1.7
mg and not more than 2.2 mg of riboflavin, not less than 27 mg and not
more than 34 mg of niacin or niacinamide, not less than 0.9 mg and not
more than 1.2 mg of folic acid, and not less than 13 mg and not more
than 16.5 mg of iron (Fe);
* * * * *
12. Section 139.122 is amended by revising the first sentence of
paragraph (a)(3) to read as follows:
Sec. 139.122 Enriched nonfat milk macaroni products.
(a) * * *
(3) Each such food contains in each pound not less than 4.0
milligrams (mg) and not more than 5.0 mg of thiamin, not less than 1.7
mg and not more than 2.2 mg of riboflavin, not less than 27 mg and not
more than 34 mg of niacin or niacinamide, not less than 0.9 mg and not
more than 1.2 mg of folic acid, and not less than 13 mg and not more
than 16.5 mg of iron (Fe). * * *
* * * * *
13. Section 139.155 is amended by revising paragraph (a)(1) to read
as follows:
Sec. 139.155 Enriched noodle products.
(a) * * *
(1) Each such food contains in each pound not less than 4
milligrams (mg) and not more than 5 mg of thiamin, not less than 1.7 mg
and not more than 2.2 mg of riboflavin, not less than 27 mg and not
more than 34 mg of niacin or niacinamide, not less than 0.9 mg and not
more than 1.2 mg of folic acid, and not less than 13 mg and not more
than 16.5 mg of iron (Fe);
* * * * *
Dated: February 26, 1996.
David A. Kessler,
Commissioner of Food and Drugs.
Donna E. Shalala,
Secretary of Health and Human Services.
[FR Doc. 96-5014 Filed 2-29-96; 12:03 pm]
BILLING CODE 4160-01-P