[Federal Register Volume 61, Number 231 (Friday, November 29, 1996)]
[Proposed Rules]
[Pages 60661-60671]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 96-30441]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
21 CFR Ch. I.
[Docket No. 96N-0364]
RIN 0905-AD91
Regulation of Medical Foods
AGENCY: Food and Drug Administration, HHS.
ACTION: Advance notice of proposed rulemaking.
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SUMMARY: The Food and Drug Administration (FDA) is soliciting comments
to initiate a reevaluation of its approach to the regulation of the
broad group of heterogeneous products that are marketed as medical
foods. FDA's goal is to arrive at a regulatory regime that will ensure
that: These products are safe for their intended uses, especially
because they are likely to be the sole or a major source of nutrients
for sick and otherwise vulnerable people; claims for these products are
truthful, not misleading, and supported by sound science; and the
labeling of these products is adequate to inform consumers about how to
use them in a safe and appropriate manner. The agency believes that
there is a need to reevaluate its policy for regulating medical foods
because of a number of developments, including enactment of a statutory
definition of ``medical food,'' the rapid increase in the variety and
number of products that are marketed as medical foods, safety problems
[[Page 60662]]
associated with the manufacture and quality control of these products,
and the potential for fraud as claims that are not supported by sound
science proliferate for these products.
DATES: Written comments by February 27, 1997.
ADDRESSES: Submit written comments to the Dockets Management Branch
(HFA-305), Food and Drug Administration, 12420 Parklawn Dr., rm. 1-23,
Rockville, MD 20857. Submit written requests for single copies of FDA's
Compliance Program for Medical Foods (Compliance Program No. 7321.002)
to the Freedom of Information Office (HFI-35), Food and Drug
Administration, 5600 Fishers Lane, Rockville, MD 20857. Send two self-
addressed adhesive labels to assist that office in processing your
requests.
FOR FURTHER INFORMATION CONTACT: Robert J. Moore, Center for Food
Safety and Applied Nutrition (HFS-456), Food and Drug Administration,
200 C St. SW., Washington, DC 20204, 202-205-4605.
SUPPLEMENTARY INFORMATION:
I. Background
One of the first medical foods to be developed was the infant
formula Lofenalac, a product that was designed for use in the
dietary management of a rare genetic condition known as phenylketonuria
(PKU). This product contains only a very limited amount of the
essential amino acid phenylalanine because the individuals with this
condition have an impaired ability to metabolize this amino acid. If
infants with PKU consume foods that contain phenylalanine, harmful end
products of phenylalanine metabolism accumulate in the body and can
cause severe, irreversible mental retardation. Dietary management to
carefully limit phenylalanine intake (for example, by using a formula
that provides only a limited, minimal amount of this essential amino
acid) can result in normal growth and development and avoid mental
retardation.
Before 1972, FDA regulated products like the infant formula
Lofenalac as drugs under section 201(g)(1)(B) of the Federal
Food, Drug, and Cosmetic Act (the act) (21 U.S.C. 321(g)(1)(B)) because
of their role in mitigating serious adverse effects of the underlying
diseases. In 1972, FDA reassessed its position. At that time, such
products were very limited in number and were being produced by a small
number of reputable manufacturers with high standards of quality
control. Additionally, the nutritional formulation requirements for
this type of product were straightforward and well established by the
medical community. FDA believed that the usefulness of these products
in patient populations was widely accepted by health care
professionals, and that close physician supervision ensured safe use in
the patient population. The agency was interested in fostering
innovation in the development of these products, most of which had been
developed for the dietary management of diseases and conditions that
are not widespread, to ensure that such products would be available at
reasonable cost.
For all these reasons, the agency concluded that a revision of its
regulatory approach to these products was appropriate. At the same
time, the agency recognized that use of these products for feeding
healthy individuals could be hazardous. For example, an infant formula
that was purposely formulated to be suitable for an infant with PKU
would be nutritionally inadequate for a normal infant. Thus, the agency
saw that it was important to differentiate these products from foods
for general use. As a result, in 1972, FDA stated that the PKU product
described above would no longer be regulated as a drug but rather as a
``food for special dietary use'' \1\ (37 FR 18229 at 18230, September
8, 1972). In addition, the agency began to follow a policy of
regulating similar types of products as foods for special dietary use.
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\1\ Although there was no statutory definition of a food for
special dietary use in 1972, the term ``special dietary uses,'' as
applied to food for humans, had been defined by regulation since
1941. In the Federal Register of November 22, 1941 (6 FR 5921), FDA
promulgated a regulation stating that the term ``special dietary
uses'', as applied to food for man, means particular (as
distinguished from general) uses of food, and that it means, among
other things, ``uses for supplying particular dietary needs which
exist by reason of a physical, physiological, pathological or other
condition, including but not limited to the conditions of disease,
convalescence, pregnancy, lactation, allergic hypersensitivity to
food, underweight, and overweight.'' This part of the regulation
remains unchanged in current Sec. 105.3(a)(1) (21 CFR 105.3(a)(1)).
The statutory definition of ``special dietary use'' in section
411(c)(3) of the act (21 U.S.C. 350(c)(3)) was added in 1976 (Pub.
L. 94-278). It defines this term as a particular use for which a
food purports or is represented to be used, including but not
limited to the following:
(A) Supplying a special dietary need that exists by reason of a
physical, physiological, pathological, or other condition, including
but not limited to the condition of disease, convalescence,
pregnancy, lactation, infancy, allergic hypersensitivity to food,
underweight, overweight, or the need to control intake of sodium.
(B) Supplying a vitamin, mineral, or other ingredient for use by
man to supplement his diet by increasing the total dietary intake.
(C) Supplying a special dietary need by reason of being a food
for use as the sole item of the diet.
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Since 1972, the legislative and regulatory history of medical foods
has reflected the agency's efforts to develop a regulatory framework to
ensure the safety and nutritional adequacy of foods that are designed
to meet distinctive nutritional requirements resulting from diseases or
health conditions. Medical foods are used under the supervision of a
physician when such distinctive nutritional requirements cannot be met
with a conventional diet. These characteristics have led the agency to
exempt medical foods from many of the requirements that apply to
conventional foods.
When FDA made nutrition labeling mandatory for certain foods in
1973, the agency exempted certain types of foods for special dietary
use from this requirement. In the preamble to the 1973 final rule on
nutrition labeling (38 FR 2124 at 2126, January 19, 1973), FDA noted
that nutrition labeling developed for foods intended for consumption by
the general population was not well suited for some food products,
including two types of foods for special dietary use: (1) Any food
represented for use as the sole item of the diet; and (2) foods
represented for use solely under medical supervision in the dietary
management of specific diseases and disorders. Therefore, this final
rule provided that these two types of foods for special dietary use
would be exempt from the general requirements for nutrition labeling
and were to be labeled in compliance with regulations that the agency
intended to include in 21 CFR part 125 (later redesignated as 21 CFR
part 105).
The Orphan Drug Amendments of 1988 enacted, for the first time, a
statutory definition of ``medical food'':
The term ``medical food'' means a food which is formulated to be
consumed or administered enterally under the supervision of a
physician and which is intended for the specific dietary management
of a disease or condition for which distinctive nutritional
requirements, based on recognized scientific principles, are
established by medical evaluation.
(21 U.S.C. 360ee(b)(3))
Although Congress provided a statutory definition for medical foods,
the legislative history of the Orphan Drug Amendments does not discuss
the definition and, therefore, does not provide any further information
regarding the types of products that the definition was intended to
cover.
In the Nutrition Labeling and Education Act of 1990 (the 1990
amendments), Congress incorporated the definition of medical foods
contained in the Orphan Drug Amendments of 1988 into section
403(q)(5)(A)(iv) of the act (21 U.S.C. 343(q)(5)(A)(iv)) and exempted
medical
[[Page 60663]]
foods from the nutrition labeling, health claim, and nutrient content
claim requirements applicable to most other foods. In the Federal
Register of November 27, 1991 (56 FR 60366 at 60377), FDA published a
proposal to implement the mandatory nutrition labeling provisions of
the 1990 amendments. The proposal discussed the statutory exemption for
medical foods and advised that the agency considered the statutory
definition of medical foods to ``narrowly constrain the types of
products that can be considered to fall within this exemption.'' In the
Federal Register of January 6, 1993, FDA published several final rules
implementing the 1990 amendments. The final rule on mandatory nutrition
labeling (58 FR 2079 at 2151, January 6, 1993) exempted medical foods
from the nutrition labeling requirements and incorporated the statutory
definition of a medical food into the agency's regulations at
Sec. 101.9(j)(8) (21 CFR 101.9(j)(8)). In this regulation, FDA
enumerated criteria that were intended to clarify the characteristics
of medical foods. The regulation provides that a food may claim the
exemption from nutrition labeling requirements only if it meets the
following criteria in Sec. 101.9(j)(8):
(i) It is a specially formulated and processed product (as opposed
to a naturally occurring foodstuff used in its natural state) for the
partial or exclusive feeding of a patient by means of oral intake or
enteral feeding by tube;
(ii) It is intended for the dietary management of a patient who,
because of therapeutic or chronic medical needs, has limited or
impaired capacity to ingest, digest, absorb, or metabolize ordinary
foodstuffs or certain nutrients, or who has other special medically
determined nutrient requirements, the dietary management of which
cannot be achieved by the modification of the normal diet alone;
(iii) It provides nutritional support specifically modified for the
management of the unique \2\ nutrient needs that result from the
specific disease or condition, as determined by medical evaluation;
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\2\ The agency notes that experience has shown that the word
that it should have used here is ``distinctive'' rather than
``unique.'' Thus, in any rulemaking that results from the advance
notice of proposed rulemaking, the agency will likely propose to
amend Sec. 101.9(j)(8) accordingly.
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(iv) It is intended to be used under medical supervision; and
(v) It is intended only for a patient receiving active and ongoing
medical supervision wherein the patient requires medical care on a
recurring basis for, among other things, instructions on the use of the
medical food.
(58 FR 2079 at 2185)
In the preamble to the final rule on mandatory nutrition labeling,
FDA noted that it had received a number of comments asking for further
clarification of the types of products that the agency considers to be
medical foods. The agency acknowledged that such clarification would be
helpful and announced that it intended to address the issue in the
future (58 FR 2079 at 2151). In the same document, the agency also
noted the need for labeling regulations for medical foods and
reiterated its intention to propose such regulations.
In 1990, the Life Sciences Research Office of the Federation of
American Societies for Experimental Biology (LSRO/FASEB) published
``Guidelines for the Scientific Review of Enteral Food Products for
Special Medical Purposes'' (Ref. 1). This report defined medical foods
as products that are distinct from foods for special dietary use in
that they ``demonstrate greater suitability for nutritional management
of a specific disease than standard enteral formulas'' and are intended
for patients with ``special medically determined nutrient requirements,
the dietary management of whom cannot be achieved by the modification
of the normal diet alone, by other foods for special dietary uses, or
by a combination thereof.'' The report proposed criteria that would
establish a strict standard that a food would have to meet to be
considered a medical food. LSRO/FASEB's proposed definition of a
medical food did not include all foods that might be useful for persons
with a disease or medical condition.
II. Reasons for Re-Evaluating Regulation of Medical Foods
A. Introduction
The agency is re-evaluating its policy for regulating medical foods
in light of several developments, including the enactment of a
statutory definition of ``medical food,'' the impact of the 1990
amendments, the rapid increase in the variety and number of products
that are marketed as medical foods and in the uses for which these
products are marketed, safety problems associated with the manufacture
and quality control of these products, and the resulting potential for
injury to consumers and fraud as claims that are not supported by sound
science proliferate for these products.
B. The Definition of ``Medical Food'' and the Impact of the 1990
Amendments: the Medical Foods Paradox
The statutory definitions of ``medical food'' (21 U.S.C.
360ee(b)(3)) and food for special dietary use (see section 411(c)(3) of
the act), and the differing treatment of these two categories of
products under the 1990 amendments to the act (i.e., medical foods are
exempted under section 403(q)(5)(A)(iv) and (r)(5)(A) of the act, while
there is no special treatment of foods for special dietary use),
establish that Congress intended that medical foods and foods for
special dietary use be viewed and regulated as separate and distinct
categories of products. Foods for special dietary use are subject to
the same nutrition labeling requirements and requirements for health
claims and nutrient content claims established for most other foods by
the 1990 amendments. Thus, foods for special dietary use, like ordinary
foods, must be labeled with certain nutrition information in a
prescribed format to ensure that such information is presented in an
informative and understandable fashion. Moreover, any nutrient content
claims or health claims on the label or in the labeling of a food for
special dietary use must have been authorized by FDA to ensure that the
claim is scientifically valid and is presented in such a way that it is
truthful and not misleading.
In contrast, under the 1990 amendments, medical foods are
specifically exempted from the requirements for nutrition labeling,
nutrient content claims, and health claims. Thus, a medical food that
is intended for the specific dietary management of a disease or
condition for which distinctive nutritional requirements have been
established may be sold without any nutrition information on its label
or labeling, and it may bear claims that have not been evaluated under
the 1990 amendments to ensure that they are scientifically valid.
Moreover, there is no assurance that the formulation of a medical food
has been evaluated prior to sale to ensure that it is suitable for the
intended patient population. The exemption from the requirements of the
1990 amendments, therefore, creates a troubling paradox: Medical foods
intended for use by sick people are subject to much less scrutiny than
virtually all other foods, which are intended for the healthy general
population. This lack of scrutiny creates a situation that could have
adverse public health consequences if these
[[Page 60664]]
products bear claims that are not scientifically valid, or if their
labeling does not disclose nutrition or other information that is
necessary for the safe and effective use of the food.
C. Universe of Products
The number and variety of products marketed as medical foods, the
number and types of claims made for such products, the types of
ingredients included in these products, and the number of manufacturers
of these products have increased significantly since the mid-1970's. In
1974, a limited survey of pharmaceutical and food manufacturers
revealed that fewer than three dozen products were being sold as
medical foods (Ref. 2). As of 1989, however, well over 200 products
were being sold as medical foods (Ref. 3). Table 1 lists several types
of products being marketed as medical foods with examples of claims
being made by vendors of these products.
However, many products marketed as medical foods may not qualify as
such under the statutory definition of medical foods. Many of these
products, for example, complete liquid nutrition products, are not
formulated or promoted for the dietary management of a particular
disease or condition but rather are formulated and marketed for use by
the general population as supplements to a normal diet or as meal
replacements.
Enteral nutrition is nutrition provided through the
gastrointestinal tract, taken by mouth or provided through a tube or
catheter that delivers nutrients beyond the oral cavity (i.e., directly
to the stomach or small intestine). This document uses the term
``enteral nutrition products'' to refer to products that have been
marketed as medical foods; ``statutory medical foods'' to refer to
enteral nutrition products that meet the statutory definition of a
medical food in section 5(b)(3) of the Orphan Drug Amendments (21
U.S.C. 360ee(b)(3)); and ``nonstatutory enteral nutrition products'' to
refer to enteral nutrition products that have been marketed as medical
foods but that do not meet the statutory definition of a medical food.
Enteral nutrition products labeled and marketed as medical foods
are generally liquid or powdered products formulated to meet specific
needs. They include nutritionally complete formulations, nutritionally
incomplete formulations (such as modular products that contain only one
nutrient or a small number of nutrients and that are intended for use
with other formulations), formulations for metabolic disorders
(including inborn errors of metabolism) in patients over 12 months of
age, and oral rehydration products. While many such products are
intended to provide a complete source of nutrition and are consumed
orally or administered by feeding tube for this use, the labeling of
such products frequently bears claims related to an intended use of the
product in the management of a disease or condition, e.g., in
alleviating specific symptoms and clinical manifestations of a
particular disease.
Table 1.--Examples of Currently Available Types of Enteral Nutrition Products for Use in Various Disease States and for Patients With Inborn Errors of
Metabolism \1\
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Disease state Patient population Product characteristics Examples of product claims
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Kidney (renal) disease (e.g., chronic or Hospitalized patients (including Type and quality of protein............ ``* * * complete balanced
acute kidney failure). critical care patients) and home care nutrition for renal
patients. patients * * * a moderate-
protein, low-electrolyte,
low-fluid, high-calorie
formula * * * designed to
provide balanced-nutrition
for dialyzed patients with
chronic or acute renal
failure * * *''
``Under careful dietary
management * * * can
maintain uremic patients in
good nutritional status,
promote anabolism and lower
and stabilize blood urea
nitrogen levels * * *''
Liver disease (e.g., coma or Hospitalized patients (including Type and quality of protein............ ``Provides adequate protein
encephalopathy associated with critical care patients) and home care without inducing or
hepatitis or cirrhosis). patients. exacerbating hepatic
encephalopathy''
An aggressive nutritional
regimen * * * may be useful
in the nutritional
management of alcoholic
liver-disease patients in
reversing malnutrition,
liver dysfunction, and
encephalopathy.''
Hypermetabolic states (e.g., severe Hospitalized patients (including Type and quality of protein; added ``A nutritionally complete
burns, trauma or infection). critical care patients). amino acids; elevated levels of formula that provides a
specific vitamins and/or minerals. concentrated source of
calories for patients with
restricted fluid allowance
or increased energy needs *
* * useful in the dietary
management of volume-
restricted patients,
oncology patients,
hypermetabolic conditions,
trauma, sepsis, and post
major surgery.''
``Specialized elemental
nutrition with glutamine
for metabolically stressed
patients with impaired GI
function * * * stimulates
intestinal epithelial cell
proliferation in injured
rats * * * diminished
mucosal atrophy associated
with injury by stimulating
intestinal cell
replacement.''
Lung disease (e.g., chronic obstructive Hospitalized patients (including High fat, low carbohydrate content..... ``A nutritionally complete,
pulmonary disease, acute respiratory critical care patients) and home care ready-to-use formula * * *
distress syndrome, cystic fibrosis). patients. uniquely formulated to
provide a diet high in
nitrogen and restricted in
carbohydrates to aid in the
control of metabolic
alterations in * * *
various stress states
including respiratory
insufficiency * * * CO2
production is minimized
while providing appropriate
nutrient levels.''
``Proven effective in the
dietary management of
patients with respiratory
disease * * * reduced CO2
production in chronic
obstructive pulmonary
disease and cystic fibrosis
patients.''
[[Page 60665]]
Compromised immune function............. Hospitalized patients (including Enriched with specific amino acids; ``Specialized complete
Human immunodeficiency virus (HIV) critical care patients) and home care fortified with increased levels of nutrition to provide
infection, acquired immune deficiency patients. vitamins. effective nutritional
syndrome (AIDS). management for people with
HIV infection or AIDS * * *
to support immune
function.''
``Increases CD4/CD8 ratio,
one aspect of immune system
* * * CD4/CD8 increased by
day 5, indicating an
improved T-helper cell
function.''
``7 days of use helped
support return of immune
function to preoperative
levels; 22 percent
reduction in mean length of
hospital stay; 70 percent
reduction in infections and
wound complications.''
Diabetes mellitus....................... Hospitalized patients (including Type and quantity of carbohydrate; high ``High fiber, low
critical care patients) and home care fiber. carbohydrate * * * for
patients. patients with abnormal
glucose tolerance * * * to
enhance blood glucose
control * * * in persons
with type I or type II
diabetes mellitus and
stress-induced
hyperglycemia.''
Malabsorption, as found in: Inflammatory Hospitalized patients (including Pre-digested macronutrients; altered ``A nutritionally complete
bowel disease (ulcerative colitis, critical care patients) and home care type or quantity of fat. enteral nutritional with *
Crohn's disease); radiation enteritis; patients. * * 85 percent of fat
short bowel syndrome. derived from (medium chain
triglyceride) (MCT) oil--a
lipid clinically proven to
result in less severity and
incidence of diarrhea and
abdominal discomfort in
individuals with fat
malabsorption * * *
resulting from conditions
such as HIV infection,
inflammatory bowel disease,
cystic fibrosis, or short
bowel syndrome.''
``Comparision of a semi-
elemental diet with
Prednisolone in the primary
treatment of active ileal
Crohn's disease * * * this
new flavored semi-elemental
diet * * * may be as
effective as steroids in
inducing remission in ideal
Crohn's disease.''
Oral rehydration solutions.............. Hospitalized patients (including Solutions of water, electrolytes and a ``To quickly restore fluids
critical care patients) and home care carbohydrate source. and minerals lost in
patients. diarrhea and vomiting in
infants and children * * *
for maintenance of water
and electrolytes following
corrective parenteral
therapy for severe
diarrhea.''
``Enteral rehydration
solution * * * to prevent
dehydration and to correct
mild to moderate
dehydration associated with
fluid and electrolyte
loss.''
``Pediatric electrolyte oral
maintenance solution * * *
to restore body water and
minerals lost in children's
diarrhea and vomiting * * *
prevents dehydration.''
Phenylketonuria (PKU)................... Patients with phenylketonuria.......... Restrict dietary phenylalanine......... ``A phenylalanine-free food
to aid in the nutritional
management of
hyperphenylalaninemia
including PKU.''
``Phenylalanine-free to
allow greater intake of
complete protein.''
``Phenylalanine-free for
pregnant women, women in
the childbearing years and
individuals over 8 years of
age.''
Maple syrup urine disease............... Patients with maple syrup urine disease Restrict dietary branched-chain amino ``To be used only for the
acids (isoleucine, leucine and valine). dietary management of
infants and children with
maple syrup urine disease
or other disorders of
branched-chain amino acid
metabolism under the direct
and continuing supervision
of a physician.''
``A branched-chain amino
acid-free medical food * *
* for nutrition support of
children and adults with
branch-chain ketoaciduria
(maple syrup urine
disease).''
``Isoleucine-, leucine- and
valine-free for individuals
over 8 years of age and
women in the childbearing
years.''
Hereditary tyrosinemia: Type I Type II.. Patients with hereditary tyrosinemia... For Type I: Restrict dietary tyrosine, ``A phenylalanine-, tyrosine-
phenylalanine and methionine;. and methionine-free
For Type II: Restrict dietary tyrosine medical food * * * for
and phenylalanine. nutrition support of
infants and toddlers with
tyrosinemia type I.''
``A special formula powder
for use in the dietary
management of hereditary
tyrosinemia II * * * a
phenylalanine- and tyrosine-
free medical food for
nutrition support of
children and adults with
tyrosinemia type II.''
``A special formula powder
for use in the dietary
management of hereditary
tyrosinemia II * * * very
low in tyrosine and
phenylalanine * * * ''
Homocystinuria.......................... Patients with homocystinuria........... Restrict dietary methionine............ ``A special diet powder
without added methionine
for dietary management of
individuals with
homocystinuria.''
``A methionine-free medical
food * * * for nutritional
support of children and
adults with vitamin B6-
nonresponsive
homocystinuria or
hypermethioninemia,''
[[Page 60666]]
``Methionine-free for
individuals over 8 years of
age and women in the
childbearing years.''
Urea cycle disorders (e.g., argininemia, Patients with urea cycle disorders..... Restrict dietary protein as tolerated ``A non-essential amino acid-
ornithine transcarbamylase deficiency, without causing hyperammonemia. free medical food * * * for
methylmalonic aciduria). nutrition support of
children and adults with a
defect in a urea cycle
enzyme * * * ''
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\1\ This is a summary description of products available for dietary management of the listed diseases and inborn errors of metabolism. Some of these
diseases and conditions have many variations, each requiring distinctive dietary restrictions or supplements to the diet. A number of products are
available for several of the listed diseases and conditions, and the actual composition of these products may vary slightly from the product
characteristics given in this summary.
D. Safety Problems
As discussed above, there has been a dramatic increase over the
past 20 years in the number and types of products that purport to be
medical foods. The number of manufacturers producing these products has
also increased. As the number of manufacturers has grown, the level of
industry experience in the current good manufacturing practice (CGMP)
and quality control procedures necessary to produce products that
contain nutrients within a narrow range of declared label values has
become quite variable. Medical foods are complex formulated products,
generally requiring sophisticated and exacting technology comparable to
that used in the manufacture of infant formulas and drugs. Moreover,
the populations that consume these products, often as the sole or a
major source of nutrition, are extremely vulnerable, e.g., pediatric
patients in periods of growth and development, the elderly, patients
who have serious illnesses, and patients in intensive care units.
Although excessive or, conversely, insufficient amounts of particular
nutrients may not be a health hazard when consumed by healthy persons,
serious adverse consequences (even death) may result when these
vulnerable populations consume these products for long, or even short,
periods of time.
Significantly, in recent years, FDA has become aware of some
serious problems with foods that purport to be medical foods. In 1986,
four infants died as a result of being fed an oral rehydration solution
that contained lethal concentrations of potassium. FDA identified the
oral rehydration solution as the cause of these deaths (Ref. 4),
inspected the site where the product was manufactured, and analyzed the
product's nutrient content. FDA determined that elevated amounts of
potassium occurred in the product because CGMP had not been followed.
Notably, weighing scales were used improperly, and persons responsible
for the formulation of product lacked adequate training.
Results of a compliance program that FDA initiated for medical
foods in 1988, and followup on adverse reactions reported to the
agency, have identified examples of deviations from CGMP that have
caused the actual nutrient content of the product to deviate
significantly from the declared label value. Some deviations have been
significant enough to create acute, life-threatening health hazards and
have led to product recalls. For example, in 1989, problems with a
nutritionally complete product containing excessive amounts of
potassium and sodium were brought to FDA's attention as a result of a
complaint from the Veterans Administration Medical Center in Nashville,
TN. Administration of this product to a patient resulted in
hyperkalemia, or elevated blood potassium levels, which can have life-
threatening consequences, including fatal cardiac arrhythmias. This
patient required intensive medical treatment to reduce blood potassium
levels and to prevent the serious side effects of hyperkalemia. FDA
inspection of the facility that had manufactured this product revealed
serious flaws in CGMP. These flaws resulted in extreme variability in
product composition between lots or individual packets of product,
which became evident when the product was analyzed by FDA for nutrient
composition. This product was recalled (Ref. 5).
In 1993, in response to a complaint to FDA from a medical center in
Seattle, WA, FDA analysis of a complete nutritional product being
administered enterally to patients in an intensive care unit revealed
that the product contained levels of potassium that were approximately
twice the amount declared on the label. The agency concluded that this
product represented an acute, potentially life-threatening hazard to
persons with impaired kidney function, particularly those who were not
being closely monitored for serum potassium levels. As a result, a
number of products were recalled (Ref. 6).
FDA is also aware of problems involving potential microbiological
contamination of products that purport to be medical foods. For
example, in 1993, a modular product containing protein and a modular
product containing carbohydrate were recalled because they had been
manufactured under conditions in which they may have become
contaminated with Salmonella (Ref. 7).
E. Claims and the Potential for Economic Fraud
FDA has not, to date, undertaken a comprehensive review of the
claims being made for products that purport to be medical foods but
rather has evaluated claims for a small number of these products on a
case-by-case basis, applying the following general principles:
1. A product marketed for use as a medical food in the dietary
management of a disease or condition should have characteristics that
are based on scientifically validated distinctive nutritional
requirements of the disease or condition.
2. There should be a scientific basis for the formulation of the
product and the claims made for the product.
3. There should be sound, scientifically defensible evidence that
the product does what it claims to do.
The agency is concerned that some of the claims made for products
that purport to be medical foods are not based on sound science, and
that consumers that use products that bear such claims, and health
professionals that recommend the use of such products, are being misled
regarding the value of these products. In addition to the health risks
created by unsafe or ineffective medical foods, consumers and third-
party payers, such as insurance companies and government
[[Page 60667]]
health care agencies, suffer significant economic losses when products
marketed as medical foods do not do what they claim to do.
A number of publications by and for health care professionals
express concern about unsupported claims for foods that purport to be
medical foods. For example, a recent edition of a book published by the
United States Pharmacopeial Convention, Inc., USP DI, Volume I, Drug
Information for the Health Care Professional (Ref. 8), lists enteral
nutrition products that are formulated to meet nutrient requirements
for individuals with specific diseases but states: ``In general,
scientific evidence for efficacy of these products is weak and requires
further study.'' The 1990 LSRO/FASEB report ``Guidelines for the
Scientific Review of Enteral Food Products for Special Medical
Purposes'' (Ref. 1) noted that products containing substances such as
essential amino acids, peptides, and medium-chain triglycerides were
available, and that such products were represented as being useful for
the dietary management of diseases and disorders. However, the report
also stated that clinical trials of these preparations were limited,
and that ``none has fully confirmed or refuted the putative advantages
of these products over ordinary nutritionally adequate preparations.''
III. Clarification of the Medical Food Definition
In the preamble to one of the proposed rules implementing the 1990
amendments, FDA advised that it considered the statutory medical food
definition to narrowly constrain the types of products that can be
considered to be medical foods (56 FR 60366 at 60377). As noted
previously in this document, however, the agency recognizes that the
universe of products that purport to be medical foods has expanded
beyond the statutory definition of a medical food to include foods that
are more appropriately foods for special dietary use. In part, this
expansion has occurred because many have difficulty distinguishing
between medical foods and foods for special dietary use. While the
agency recognizes that some ambiguity exists in the distinction between
these two types of foods, the statutory language provides several bases
on which to distinguish medical foods from foods for special dietary
use.
A. ``Distinctive Nutritional Requirements''
A fundamental element of the medical food definition that
distinguishes this type of product from a food for special dietary use
is the statutory requirement that a medical food be intended to meet
distinctive nutritional requirements of a disease or condition. Under
21 U.S.C. 360ee(b)(3), distinctive nutritional requirements must be
based on recognized scientific principles and established by medical
evaluation. The law does not define what constitutes a ``distinctive
nutritional requirement,'' however, and there is more than one possible
interpretation. FDA welcomes public comment on what definition of
``distinctive nutritional requirement'' will best protect and promote
the public health. The agency is suggesting two possible
interpretations of this phase.
1. Physiological Interpretation of ``Distinctive Nutritional
Requirement''
``Distinctive nutritional requirement'' may be interpreted to refer
to the body's requirement for specific amounts of nutrients to maintain
homeostasis (the state of equilibrium in the body with respect to
various functions and to the chemical compositions of the fluids and
tissues) and sustain life; that is, the amount of each nutrient that
must be available for use in the metabolic and physiological processes
necessary to sustain life.
The nutritional requirements of healthy people for specific
nutrients reflect their quantitative and qualitative requirements for
absorbed nutrients (i.e., the physiological requirement for the
nutrient), with adjustments for common inefficiencies associated with
absorption, metabolism, and retention. However, the dietary management
of patients with specific diseases requires, in some instances, the
ability to meet nutritional requirements that differ substantially from
the needs of healthy persons. For example, in establishing the
recommended dietary allowances for the general, healthy population, the
Food and Nutrition Board of the Institute of Medicine, National Academy
of Sciences recognized that different or distinctive physiologic
requirements may exist for certain persons with ``special nutritional
needs arising from metabolic disorders, chronic diseases, injuries,
premature birth, other medical conditions, and drug therapies'' (Ref.
9). Thus, the distinctive nutritional needs associated with a disease
reflect the total amount needed by a healthy person to support life or
maintain homeostasis, adjusted for the distinctive changes in the
nutritional needs of the patient as a result of the effects of the
disease process on absorption, metabolism, and excretion. These
distinctive nutritional requirements may be greater than, less than, or
in a narrower range of tolerance than for an otherwise healthy
individual.
Under this physiological interpretation of ``distinctive
nutritional requirements, ``medical foods'' are foods that are
formulated to aid in the dietary management of a specific disease or
health-related condition that causes distinctive nutritional
requirements that are different from the nutritional requirements of
healthy people. Foods for special dietary use, on the other hand, are
foods that are specially formulated to meet a special dietary need,
such as a food allergy or difficulty in swallowing, but that provide
nutrients intended to meet ordinary nutritional requirements. The
special dietary needs addressed by these foods do not reflect a
nutritional problem per se; that is, the physiological requirements for
nutrients necessary to maintain life or homeostasis addressed by foods
for special dietary use are the same as those of normal, healthy
persons. These foods are formulated in such a way that only the
ingredients or physical form of the diet is different. For example, a
person who has difficulty swallowing solid food may have a special
dietary need for a food that is in liquid form, but this special
dietary need does not change his or her physiologic nutrient
requirements. Similarly, a person who is allergic to specific food
proteins (e.g., gluten) may need foods specially formulated not to
contain these proteins. However, the specially formulated food still
would provide the same amount of protein (i.e., amino acids) as is
needed by the general population because the quantitative and
qualitative amount of protein required by the body is similar in both
healthy and protein-sensitive patients. Thus, foods for special dietary
use are foods that are intended to meet ordinary nutritional
requirements through special dietary means.
2. Alternative Interpretation of ``Distinctive Nutritional
Requirement''
``Distinctive nutritional requirement'' may also be interpreted to
encompass physical or physiological limitations in a person's ability
to ingest or digest conventional foods, as well as distinctive
physiological nutrient requirements. The FASEB report on medical foods
stated that medical foods are for ``patients with limited or impaired
capacity to ingest, digest, absorb, or metabolize ordinary foodstuffs
or certain nutrients contained therein, or (who) have other special
medically determined nutrient requirements'' (Ref. 1). This definition
would include uses that a purely
[[Page 60668]]
physiological definition of ``distinctive nutritional requirements''
would exclude, such as foods intended for persons not able to ingest
foods in certain physical forms (e.g., solid food), foods intended for
persons who need a concentrated form of nutrition because of reduced
appetite as a result of disease or convalescence), or foods intended
for persons who may have other physical limitations on the amount or
composition of food that they can consume. Although these types of
conditions do not necessarily result in nutrient needs different from
those of healthy persons, they represent a situation where it may be
necessary that the food be formulated and manufactured within very
narrow tolerances to ensure that the food provides most or all of the
essential nutrients, as the persons for whom the food is intended may
not be able to eat a variety of foods to ensure that they meet their
nutrient requirements.
Therefore, it may be appropriate to define ``distinctive
nutritional requirements'' to include those requirements that result
from a disease or condition that cause a physical or physiological
limitation in the ability of a person to ingest or digest conventional
nutrient sources and result in that person needing specially formulated
foods to meet part or all of their daily nutrient needs. Defining this
term in this way may be appropriate because these circumstances create
nutritional needs that are more narrowly defined than those of healthy
persons, because the patient is relying on only a limited number of
foods or a single food for sustenance. The agency asks for comments on
whether persons with an impaired ability to ingest or digest specific
foods because of a disease or condition, or who have physical or
physiological limitations that cause them to rely on an enteral
nutrition product for a significant part or all of their nutrient
needs, have ``distinctive nutritional requirements'' within the meaning
of the medical food definition.
B. ``Under the Supervision of a Physician''
The second element of the medical food definition that
distinguishes a medical food from a food for special dietary use is the
statutory requirement that a medical food be ``formulated to be
consumed or administered enterally under the supervision of a
physician.'' As stated in the preamble to the proposed rule
implementing the nutrition labeling requirements of the 1990 amendments
(56 FR 60366 at 60377), ``under the supervision of a physician'' means
that the intended use of a medical food is for the dietary management
of a patient receiving active and ongoing medical supervision (e.g., in
a health care facility or as an outpatient). The physician determines
that the medical food is necessary to the patient's overall medical
care, and the patient consults the physician on a recurring basis.
Medical foods are intended for the dietary management of patients
who have a short-term or long-term medical need for a particular
nutrient or combination of nutrients to meet distinctive nutritional
requirements. The use of a medical food requires ongoing physician
oversight to ensure that the food effectively meets the distinctive
nutritional requirements of the patient's disease or condition, and
that the use of an enteral medical food is the appropriate means (i.e.,
as opposed to a patient requiring a parenteral nutrition product) to
meet the patient's distinctive nutritional requirements. Therefore,
medical foods are foods that are an integral component of the clinical
management of a patient. Medical foods are not foods simply recommended
by a physician as part of an overall diet designed to reduce the risk
of a disease or medical condition, to lose or maintain weight, or to
ensure the consumption of a healthy diet. Foods recommended by a
physician for these purposes may be foods for special dietary use, but
they are not medical foods.
C. ``Specific Dietary Management''
The third fundamental element of the definition of a medical food
that distinguishes a medical food from a food for special dietary use
is the statutory requirement that a medical food be intended for the
specific dietary management of a disease or condition. The term
``specific dietary management'' in the statutory definition of medical
foods evidences that Congress intended these foods to be an integral
part of the clinical treatment of patients. Consistent with this
interpretation of this term, the LSRO/FASEB Panel concluded that the
objectives of incorporating the use of medical foods into patient
management were, in part, to ``ameliorate clinical manifestations of
the disease,'' ``favorably influence the disease process,'' and
``positively influence morbidity and mortality (patient outcomes)''
(Ref. 1). There is no language corresponding to ``specific dietary
management'' in the statutory definition applicable to foods for
special dietary use. Thus, although they may be useful in supplying the
special dietary needs of patients who have a disease or other condition
that prevents them from eating normally, foods for special dietary use,
unlike medical foods, are not specifically tailored for use as the
nutritional component of the patient's treatment.
D. Summary
The statutory definitions of medical foods and foods for special
dietary use overlap to the extent that both categories encompass foods
that are intended for use by sick people. The differences in the
statutory definitions evidence, however, that Congress intended foods
for special dietary use under section 411(c)(3)(A) of the act to be a
broader category of foods for use by people with special dietary needs
or desires, while it intended medical foods to be a narrower category
of foods for use by people with particular diseases or conditions that
have distinctive nutritional requirements. Since a medical food must
address the ``distinctive nutritional requirements'' of a disease or
condition, a medical food is suitable only for use by patients with
that disease or condition. Of course, it is possible for more than one
disease or condition to create the same distinctive nutritional
requirements. A product that is intended to address the distinctive
nutritional requirements of a particular disease is a medical food,
even though some of those requirements may also be created by other
diseases. A product that is designed to address a problem that is
common to several diseases, but not the full range of requirements of
any specific disease, would be a food for special dietary use. For
example, the distinctive nutritional requirements of burn patients
include a greater energy requirement due to hypermetabolism and a
requirement for dietary glutamine because endogenous synthesis of this
amino acid does not meet the metabolic requirement. Thus, a product
formulated to meet the higher energy requirement due to the
hypermetabolic state, but which does not meet the requirement for
glutamine, would be a food for special dietary use and not a medical
food because it does not meet the full range of distinctive nutritional
requirements in patients with burn injuries.
IV. Need for Substantiation of Nutritional Efficacy and Claims Made in
Product Labeling
Because of their intended use in supplying the distinctive
nutritional needs of patients who are ill or otherwise medically
vulnerable, it is essential that medical foods be appropriately
formulated for the particular disease or condition for
[[Page 60669]]
which they are labeled. Moreover, because the statutory definition of a
medical food provides that these foods are part of the clinical
management of a disease or condition, the definition necessarily
incorporates a requirement that the product actually meet the
distinctive nutritional requirements for the disease or condition. It
is not enough that a manufacturer merely declare or subjectively intend
that the product be used for the dietary management of patients with
certain diseases or conditions. If the product, as formulated and
consumed, does not actually meet those distinctive requirements, it
would violate the act. Under any other view, the medical foods category
would merely create a safe harbor for fraudulent claims targeted at
those who are most vulnerable.
Other elements of the statutory definition support this view. In
defining the term ``medical food'' in the Orphan Drug Amendments,
Congress included the requirement that distinctive nutritional
requirements of a disease or condition exist, and that they be based on
recognized scientific principles and established by medical evaluation.
Thus, Congress established a strict standard for when a food qualifies
as a medical food. The establishment of this strict standard for
distinctive nutritional requirements necessarily implies an expectation
that this standard will in fact be met.
Acceptance of the manufacturer's intent that the product meets the
special needs of the disease, without objective information to support
the manufacturer's intent, would establish a subjective standard that
would provide no assurance that the statutory standard has been met.
Moreover, such a standard would ignore the fundamental differences
between a medical food and other types of food. As stated above, a
medical food is intended for use as the source of nutrients that are
necessary in the medical management of a particular disease or
condition. Thus, it is crucial to the health of the patient. No other
type of food, including food for special dietary use, has such a direct
relationship to the health of an individual. It is therefore necessary
that the physician be able to rely on the medical food to effectively
meet the distinctive nutritional requirements of the patient.
Finally, the statutory scheme for regulation of claims relating to
health and disease confirms the appropriateness of a strong standard
for substantiation of the nutritional efficacy of medical foods. The
act establishes a range of circumstances under which claims relating to
health and disease may be made. At one end of the spectrum are
conventional foods, which under section 403(r) of the act may bear a
health claim only if FDA determines:
based on the totality of publicly available scientific evidence
(including evidence from well-designed studies conducted in a manner
which is consistent with generally recognized scientific procedures
and principles) that there is significant scientific agreement,
among experts qualified by scientific training and experience to
evaluate such claims, that the claim is supported by such evidence.
At the other end of the spectrum are drugs, whose effectiveness in
diagnosing, curing, mitigating, treating, or preventing disease must be
established by substantial evidence, defined as:
evidence consisting of adequate and well-controlled investigations,
including clinical investigations, by experts qualified by
scientific training and experience to evaluate the effectiveness of
the drug involved, on the basis of which it could fairly and
responsibly be concluded by such experts that the drug will have the
effect it purports or is represented to have under the conditions of
use prescribed, recommended, or suggested in the labeling or
proposed labeling thereof.
(Section 505(d)(7) of the act (21 U.S.C. 355(d)(7)).)
Clearly, medical foods fall somewhere between these two points, and the
statutory scheme therefore requires some level of substantiation for a
medical food's claimed usefulness in the dietary management of disease.
When Congress enacted authorization for health claims on
conventional foods, it provided that such claims would be permitted
only if FDA determined that the substance-disease relationship that is
the subject of the claim is supported by significant scientific
agreement among experts. The House Report for the 1990 Amendments
states: ``The standard is intended to be a strong one. The bill
requires that the Secretary have a high level of confidence that the
claim is valid'' (Ref. 10). The establishment of a ``strong''
scientific standard was necessary to ensure that claims were supported
by adequate scientific evidence so that they would not be misleading,
and so that consumers could have confidence in the scientific validity
of the claimed substance-disease relationship. Thus, even a health
claim for a food intended to be used by healthy individuals must meet a
high standard.
The reasons for requiring a strong standard of substantiation apply
with even more force to medical foods. The statutory definition of a
medical food states that such a food must be intended for the specific
dietary management of a disease or condition for which distinctive
nutritional requirements, based on recognized scientific principles,
are established by medical evaluation. As discussed earlier, this
aspect of the definition makes it clear that Congress intended that
claims made for medical foods be supported by scientific evidence, and
it also constitutes a scientific standard that must be met for a food
to be a medical food. The nature of these products (i.e., their
intended use in the nutritional management of people affected by a
disease or other condition) and the exemptions (i.e., from health claim
requirements applicable to conventional foods) provided for them by
virtue of their status as medical foods necessitate at least as much
substantiation to support claims made for medical foods as for health
claims on conventional foods. It would make no sense to establish a
standard for claims on medical foods that was lower than the standard
for health claims that are made for foods sold to healthy people.
The agency is concerned that many claims made for products marketed
as medical foods are not supported by adequate scientific evidence, and
that these unsupported claims result in the inappropriate use of some
products by patients and physicians when effective alternative
nutritional strategies for managing the disease are available. One
medical expert on enteral nutrition formulas voiced this concern by
stating that since the:
introduction of nutritional support * * * as a specific therapeutic
entity in the 1960's, a number of claims have been made, and widely
believed, regarding its ability to improve the natural history of
many diseases. However, these claims have been disseminated in the
absence of supportive data from prospective randomized controlled
trials * * *; in fact, when such studies have been performed, they
have by and large not been able to demonstrate that [nutritional
support] does improve morbidity and/or mortality.
(Ref. 11)
A physician relies on the claims made for medical foods on their
labels and in their labeling as a significant factor in deciding
whether to use a particular medical food in the clinical management of
a patient. Thus, it is essential that the claims made for such a
product present an accurate interpretation of the scientific evidence
concerning the usefulness of that product or specific formulation. It
is critical for the safe and appropriate use of the medical food that
the claims made for it are accurate and unbiased, and that they are
based on a critical
[[Page 60670]]
evaluation of the science available to the manufacturer. The need for
physicians and patients to have confidence that any claim that a
product is a medical food formulated for the specific dietary
management of a disease or condition requires that a strong standard of
substantiation be in place. A strong standard of substantiation would
be one that requires that all pertinent data be considered in the
formulation of the product and in the development of any claims about
its use.
Further, the misbranding provisions of the act do not permit a
food, including a medical food, to bear misleading labeling claims
(section 403(a) of the act). Claims may be misleading not only because
of affirmative representations made in the labeling, but also because
the labeling fails to reveal facts material in the light of such
representations with respect to consequences which may result from the
use of the food under the conditions of use prescribed in the labeling
or under usual or customary conditions of use (section 201(n) of the
act). Thus, a medical food that bears claims that are not based on all
the information available, and that do not permit the consumer or
physician to make an informed choice, may be misbranded.
In summary, the intended uses of medical foods, the statutory
definition of a medical food, and the statutory scheme for regulating
health and disease claims all point to the need for a strong standard
of scientific evidence for the composition and effectiveness of medical
foods to provide assurance to health care providers and patients of the
nutritional utility of these products. The standard should be no less
demanding than for health claims for foods intended for the healthy
general population. Moreover, because medical foods are intended for
use in the clinical management of seriously ill and injured patients,
it may be appropriate and necessary to apply a more stringent standard
to the scientific evidence used to support claims made for medical
foods. The agency's preliminary view is that the scientific standard
contained in the statutory medical food definition may require some of
the same types of data for medical foods as are needed to support drug
claims (e.g., data from clinical investigations). The agency asks for
comments regarding how stringent a scientific standard is necessary to
ensure the safe and appropriate use of a medical food for a particular
disease or condition.
V. Agency Plans
The agency is soliciting comments to initiate a reevaluation of its
approach to the regulation of the broad group of heterogenous products
marketed as medical foods and whether this approach serves the best
interests of the consumers of such products. If the current regulatory
approach is not adequate, the agency is interested in how it can
improve the regulatory regime for medical foods to best serve those
interests. FDA will review and consider all comments received. While
this reevaluation is ongoing, however, the agency advises that it
intends to continue to take regulatory action when necessary to protect
consumers from unsafe or fraudulent products marketed as medical foods.
VI. Economic Issues
Under Executive Order 12866, FDA will be required to consider the
costs and benefits of any proposed regulations pertaining to medical
foods when regulations are proposed. In addition, under the Regulatory
Flexibility Act and the Small Business Regulatory Enforcement and
Fairness Act, FDA will be required to consider the impacts on small
entities of any such regulations.
The primary benefit of any proposed change in the requirements
applicable to medical foods will be a reduction in the health risks
posed by medical foods that meet existing requirements. In addition,
changes in the requirements applicable to medical foods that specify
the level of scientific support required to make claims concerning the
product will mean that consumers will have assurance that the claims
are valid, and that the claims that are made provide reliable
information. Other benefits will derive from the elimination of
fraudulent and unsupported claims which will save consumers and third-
party payers money and will improve patient health because people will
use products that are appropriate for their conditions instead of
relying on those bearing unsupported claims that do not have a positive
impact on their conditions.
FDA asks for comments and information on the current health risks
posed by medical foods meeting existing CGMP, labeling, and other
applicable regulations. FDA also asks for comments on the degree to
which these health risks may be reduced by additional regulation of
medical foods, such as quality control requirements and additional CGMP
and labeling regulations.
The primary cost of any proposed change will be the difference
between the current cost of producing and marketing medical foods and
the anticipated cost of producing and marketing medical foods under the
proposed change. For example, relevant costs may include the cost of
changing labels, generating particular types of information for labels,
changing production methods or facilities to accommodate new CGMP
requirements, the generation of additional information to establish
product safety and effectiveness, and the cost of any uncertainty or
delays associated with a potential premarket notification process.
FDA asks for comments on the costs that would be generated if
medical foods were subject to additional regulatory requirements, such
as quality control requirements, specific CGMP requirements, and
labeling regulations. FDA also asks for comments on the impacts on
small entities that would result if medical foods were subject to
additional regulatory requirements of the type discussed in this
document.
VII. Summary
Patients rely on medical foods to meet the distinctive nutritional
needs resulting from their disease or condition, and, therefore,
medical foods are often a significant part of the clinical management
of these patients. Despite the importance of medical foods, however,
existing regulations do not provide clear guidance on what products
should be considered to be medical foods or on requirements to ensure
that these foods do what they purport to do and are safe for their
intended use. There is no regulatory framework that establishes
specific quality assurance requirements, ensures the safety of medical
foods under their intended conditions of use, ensures that they provide
the nutrients that they claim to provide within safe ranges, or ensures
that the benefits claimed for their purported use are supported by
adequate scientific evidence. Therefore, the agency asks for comments
on the following questions:
1. Is FDA's current approach to the regulation of medical foods
adequate to ensure that food products claimed to be medical foods are
safe and that the claims that they bear are valid? Is there a need for
FDA to change its approach to the regulation of medical foods to better
serve the needs of the patient populations that consume such products,
and if so, what should the regulatory regime for medical foods be?
2. What factors should FDA consider applying as criteria to
determine what products meet the statutory definition of a medical
food? Should the agency apply a physiological interpretation of
``distinctive nutritional requirements'' in determining whether a
product is a medical food, or should medical foods also include
products that are used for
[[Page 60671]]
patients with ingestion or digestion problems but with otherwise
``normal'' nutrient requirements? Would the latter interpretation be
consistent with the act?
3. What requirements are necessary to ensure the safe and
appropriate use of: (a) Products that meet the statutory definition of
a medical food? (b) products that have been marketed as medical foods
but that do not meet the statutory definition of a medical food?
Examples might include requirements that address product
composition, current good manufacturing practice and quality control
procedures, labeling requirements, and standards governing claims about
the product and for foods that may be used as a sole item of the diet.
4. To ensure the safety and effectiveness of a medical food, should
the agency require that the manufacturer notify FDA before marketing
the product, and that it submit evidence that establishes that the
product will be safe for its intended use and that any claims made for
the product are supported by sound science? What information should be
included in such a submission?
5. What standard should be used to determine the safety of a
medical food?
6. What quantity and quality of scientific evidence should be
required to establish that a disease or condition has distinctive
nutritional requirements based on recognized scientific principles?
7. What quantity and quality of scientific evidence should be
required to support the validity of claims made for medical foods?
8. What information should be included on the label of a medical
food or otherwise disclosed to health care professionals and consumers?
Should the amount and detail of the information to be disclosed depend
on the types of claims made for the medical food or on other
characteristics of the product? What methods would be most effective in
communicating information on the intended uses, benefits, and other
characteristics of a medical food to enable physicians and consumers to
make informed decisions regarding its use (e.g., labels, package
inserts, detailed summaries of the science upon which a firm is basing
the claims made for its product)?
9. Should the agency develop regulations specifying quality control
standards and procedures and current good manufacturing practice
requirements for medical foods? What types of requirements are
necessary (e.g., expiration dating, analysis of nutrient content,
microbiological safety measurements, etc.)?
10. How should FDA monitor the safety and effectiveness of medical
foods already on the market? What elements are necessary components of
an effective postmarket surveillance system for these products? Should
a postmarket surveillance system for medical foods include requirements
and procedures for the collection and reporting to FDA of safety- and
efficacy-related product defects, adverse reaction reports, and
complaints by health care professionals and consumers? Should
manufacturers be required to collect information describing the
outcomes associated with the use of medical food products in designated
patient categories that would be available to FDA, health care
providers, and consumers?
VIII. Comments
Interested persons may, on or before February 27, 1997, submit to
the Dockets Management Branch (address above) written comments
regarding this proposal. Two copies of any comments are to be
submitted, except that individuals may submit one copy. Comments are to
be identified with the docket number found in brackets in the heading
of this document. Received comments may be seen in the office above
between 9 a.m. and 4 p.m., Monday through Friday.
IX. 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. Talbot, J. M., ``Guidelines for the Scientific Review of
Enteral Food Products for Special Medical Purposes,'' prepared for
the Food and Drug Administration under FDA Contract No. 223-88-2124
by the Life Sciences Research Office, Federation of American
Societies for Experimental Biology, Bethesda, MD, 1990.
2. Fisher, K. D., J. M. Talbot, and C. J. Carr, ``A Review of
Foods for Medical Purposes: Specially Formulated Products for
Nutritional Management of Medical Conditions,'' prepared for the
Food and Drug Administration under Contract No. FDA 223-75-2090 by
the Life Sciences Research Office, Federation of American Societies
for Experimental Biology, Bethesda, MD, 1977.
3. Hattan, D. G., and D. R. Mackey, ``A Review of Medical Foods:
Enterally Administered Formulations Used in the Treatment of
Diseases and Disorders,'' Food Drug Cosmetic Law Journal, 44:479-
502, 1989.
4. Health Hazard Evaluation No. 1470, Food and Drug
Administration, Center for Food Safety and Applied Nutrition, 200 C
St. SW., Washington, DC, April 25, 1986.
5. FDA Enforcement Report, August 23, 1989, Rockville, MD.
6. FDA Enforcement Report, May 19, 1993, Rockville, MD.
7. FDA Enforcement Report, July 28, 1993, Rockville, MD.
8. The United States Pharmacopeial Convention, Inc., USP DI,
Drug Information for the Health Care Professional, Volume I, Rand
McNally, Taunton, MS, 1996.
9. Subcommittee on the Tenth Edition of the RDA's, Food and
Nutrition Board, Commission on Life Sciences, National Research
Council, ``Recommended Dietary Allowances, 10th ed.,'' National
Academy Press, Washington, DC, 1989.
10. H. Rept. 101-538, 101st Cong., 2d sess., 19, ``Nutrition
Labeling and Education Act of 1990,'' June 13, 1990.
11. Koretz, R. L., A Critical Look at the Trials, Symposium #2,
Immunonutrition in the ICU, In: Proceedings of the 19th Clinical
Congress, American Society for Parenteral and Enteral Nutrition,
Miami, FL, pp. 97-103, 1995.
This document is issued under sections 4, 5, and 6 of the Fair
Packaging and Labeling Act (15 U.S.C. 1453, 1454, 1455); sections 201,
301, 402, 403, 404, 405, 409, 411, 412, 501, 502, 503, 505, and 701 of
the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 321, 331, 342, 343,
344, 345, 348, 350, 350a, 351, 352, 353, 355, 371); and 21 U.S.C.
360ee(b)(3) (section 5(b)(3) of the Orphan Drug Amendments of 1988, as
amended by Pub. L. 100-290).
Dated: October 31, 1996.
William B. Schultz,
Deputy Commissioner for Policy.
[FR Doc. 96-30441 Filed 11-27-96; 8:45 am]
BILLING CODE 4160-01-P