[Federal Register Volume 73, Number 146 (Tuesday, July 29, 2008)]
[Notices]
[Pages 43937-43940]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: E8-17356]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
[Docket No. FDA-2008-N-0389]
Food and Drug Administration Amendments Act of 2007; Prohibition
Against Food to Which Drugs or Biological Products Have Been Added;
Request for Comments
AGENCY: Food and Drug Administration, HHS.
ACTION: Notice; request for comments.
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SUMMARY: The Food and Drug Administration (FDA) is requesting comments
relevant to the implementation of section 912 of the Food and Drug
Administration Amendments Act of 2007 (FDAAA). Section 912 of FDAAA
establishes section 301(ll) in the Federal Food, Drug, and Cosmetic Act
(the act), which prohibits the interstate shipment of certain foods to
which an approved drug or a licensed biological product has been added.
Section 301(ll) also prohibits the interstate shipment of foods
containing an added drug or a biological product that has been the
subject of substantial clinical investigations, the existence of which
has been made public. FDA requests that interested persons submit data,
information, and comments that will help provide a context for the
agency's decisions on implementation of this provision. To encourage
responsive comments, FDA is including a series of questions for
interested persons to consider in preparing comments.
DATES: Submit written or electronic comments by October 27, 2008.
ADDRESSES: Submit written comments, data, and other information to the
Division of Dockets Management (HFA-305), Food and Drug Administration,
5630 Fishers Lane, rm. 1061, Rockville, MD 20852. Submit electronic
comments to www.regulations.gov.
FOR FURTHER INFORMATION CONTACT: Catherine L. Copp, Center for Food
Safety and Applied Nutrition (HFS-4), Food and Drug Administration,
301-436-1589, e-mail: catherine.copp@ fda.hhs.gov.
SUPPLEMENTARY INFORMATION:
I. Background
On September 27, 2007, the Food and Drug Administration Amendments
Act of 2007 (Public Law 110-85) (FDAAA) was enacted. Section 912 of
FDAAA establishes section 301(ll) in the Federal Food, Drug, and
Cosmetic Act (the act), 21 U.S.C. 331(ll), which adds the following
prohibited act to section 301.21 U.S.C. 331:
The introduction or delivery for introduction into interstate
commerce of any food to which has been added a drug approved under
section 505, a biological product licensed under section 351 of the
Public Health Service Act, or a drug or a biological product for which
substantial clinical investigations have been instituted and for which
the existence of such investigations has been made public, unless--
(1) such drug or such biological product was marketed infood
before any approval of the drug under section 505, beforelicensure
of the biological product under such section 351, andbefore any
substantial clinical
[[Page 43938]]
investigations involving thedrug or the biological product have been
instituted;(2) the Secretary, in the Secretary's discretion,
hasissued a regulation, after notice and comment, approving the
useof such drug or such biological product in the food;(3) the use
of the drug or the biological product in thefood is to enhance the
safety of the food to which the drug orthe biological product is
added or applied and not to haveindependent biological or
therapeutic effects on humans, and theuse is in conformity with--
(A) a regulation issued under section 409prescribing conditions
of safe use in food;(B) a regulation listing or affirming
conditionsunder which the use of the drug or the biologicalproduct
in food is generally recognized as safe;(C) the conditions of use
identified in anotification to the Secretary of a claim of
exemptionfrom the premarket approval requirements for foodadditives
based on the notifier's determination that theuse of the drug or the
biological product in food isgenerally recognized as safe, provided
that theSecretary has not questioned the general recognition
ofsafety determination in a letter to the notifier;(D) a food
contact substance notification that iseffective under section
409(h); or(E) such drug or biological product had beenmarketed for
smoking cessation prior to the date of theenactment of the Food and
Drug Administration AmendmentsAct of 2007; or
(4) the drug is a new animal drug whose use is not unsafeunder
section 512.
Section 301(ll) makes it a prohibited act to ship in interstate
commerce certain foods to which an approved drug or a licensed
biological product has been added. Section 301(ll) also prohibits the
interstate shipment of certain foods containing an added drug or a
biological product that has been the subject of substantial clinical
investigations, the existence of which has been made public. Under the
act, persons who commit a prohibited act may be enjoined, 21 U.S.C.
332, or prosecuted criminally, 21 U.S.C. 333. In addition, a food which
may not, under the provisions of section 301(ll), be introduced or
delivered for introduction into interstate commerce, is subject to
seizure and forfeiture, 21 U.S.C. 334, and under 21 U.S.C. 381, a food
offered for import into the United States that appears to be prohibited
from introduction or delivery for introduction into interstate commerce
under section 301(ll) is subject to refusal of admission.
The language of section 301(ll) has a number of parallels to, as
well as significant differences from, the language of a similar
provision in section 201(ff)(3)(B) (21 U.S.C. 321(ff)(3)(B)), which is
part of the act's definition of ``dietary supplement.'' Although there
is legislative history of FDAAA, including a report from the House
committee with jurisdiction (H. Rep. No. 225, 110th Cong., 2d Sess.
(2007)), section 301(ll) is not addressed in that legislative history.
The Secretary of Health and Human Services has delegated to the
Commissioner of Food and Drugs the principal responsibility for
administering the act. As the administering agency, it is FDA's
responsibility generally to implement amendments to the act, including
the amendments made by section 912 of FDAAA.
Section 301(ll) presents a number of questions of statutory
interpretation for FDA to consider. The scope of the agency's
discretion to interpret section 301(ll) is defined by the Supreme
Court's decision in Chevron U.S.A., Inc. v. Natural Resources Defense
Council, Inc., 467 U.S. 837 (1984). Under Chevron, if the language of a
statute makes Congressional intent on a particular question clear and
unambiguous, the agency charged with administering the statute must
give effect to that intent. Chevron, 467 U.S. at 842-43. If the statute
is silent or ambiguous on the question, however, the agency is
permitted to give the statute a reasonable construction, Chevron, 467
U.S. at 844-845, and that construction is entitled to deference.
Chevron, 467 U.S. at 844.
II. Questions Presented
FDA believes that a fuller understanding of the impact of various
interpretations of section 301(ll) would be beneficial as the agency
considers how to implement this new provision. Accordingly, FDA is
requesting that interested persons submit data, information, and other
comments regarding possible approaches to implementation. To guide
those submissions and responses, the agency has prepared the following
questions. FDA suggests that, in preparing responses to this request
for comments, interested persons consider the following:
A. Food
Section 301(ll) prohibits the introduction or delivery for
introduction into interstate commerce of certain ``food.'' Under
section 201(f), ``food'' means articles used for food or drink for man
or other animals, chewing gum, and articles used for components of such
articles. Food includes human food, including infant formula, medical
foods, and dietary supplements; food contact substances, including food
packaging; and animal feed, including pet food and feed ingredients.
Consistent with the broad definition of ``food'' in section 201(f), FDA
seeks information about the impact of section 301(ll) on food in all
its forms, including food ingredients, categories of food, and finished
food products.
1. What types or categories of food would likely be subject to the
prohibition of section 301(ll)? What types or categories are likely to
be unaffected by section 301(ll)? If possible, please provide specific
examples of these foods.
2. What is the likely impact of applying section 301(ll) to infant
formula? Are there substances used or potentially used in infant
formula that would be prohibited from such use by section 301(ll)?
3. What is the likely impact of applying section 301(ll) to dietary
supplements? Are there substances used or potentially used in or as
dietary supplements that would be prohibited from such use by section
301(ll)? What would be the advantages and disadvantages of applying
both section 301(ll) and section 201(ff)(3)(B) to dietary supplements?
Would such an approach lead to more effective regulation or less
effective regulation of these products, and why?
4. What is the likely impact of applying section 301(ll) to animal
feed? Are there substances used or potentially used in animal feed,
including pet food and feed ingredients, that would be prohibited from
such use by section 301(ll)?
5. What is the likely impact of interpreting ``food'' in section
301(ll) to include food contact substances, including packaging
components that meet the definition of a food additive? Are there
substances used or potentially used in food packaging or other food
contact substances that would be prohibited from such use by section
301(ll)?
B. Previously Marketed Foods Now Barred from Interstate Commerce
Section 301(ll) identifies a category of foods that can no longer
be introduced or delivered for introduction into interstate commerce
although these foods were allowed in interstate commerce before the
enactment of FDAAA. Specifically, if a food contains a substance that
is an approved drug, that is a licensed biological product, or that has
been the subject of substantial clinical investigations that have been
made public, and if the substance was added to the food to have an
independent biological or therapeutic effect on the person consuming
it, rather than to enhance the safety of the food, the food is now
barred from interstate commerce if any substantial clinical
investigations of the substance were instituted, or the drug was
approved or
[[Page 43939]]
the biologic was licensed, prior to the first marketing of the
substance in food. FDA seeks information on foods in this category that
were legally marketed prior to the enactment of FDAAA but that are now
barred from interstate commerce.
1. How many and what types of foods would be affected? What would
be the impact on businesses that produce and sell these foods?
2. What would be the impact on consumers who currently use the
products?
3. If possible, please provide specific examples of affected foods.
C. Drug
Section 301(ll) prohibits the introduction or delivery for
introduction into interstate commerce of food to which has been added a
``drug approved under section 505.''
Implementing section 301(ll)'s restrictions on adding approved
drugs to food will require FDA to consider how the identity of a
``drug'' is to be determined for purposes of section 301(ll).
1. What would be the impact of deeming two substances to be
identical if they are chemically identical?
2. Are there approved drugs that cannot be identified by their
chemical structure? If so, what would be a scientifically accurate and
technically feasible way for FDA to determine the identity of the
``drug approved under section 505'' or ``drug * * * for which
substantial clinical investigations have been instituted'' and consider
whether that drug was marketed in food before the drug's approval by
FDA or before the initiation of the substantial clinical
investigations? Which drugs or classes of drugs cannot be identified by
their chemical structure?
D. Biological Product
Section 301(ll) prohibits the introduction or delivery for
introduction into interstate commerce of food to which has been added a
``biological product licensed under section 351 of the Public Health
Service Act.'' Under section 351(i) of the Public Health Service Act
(PHS Act) (42 U.S.C. 262(i)), a ``biological product'' means ``a virus,
therapeutic serum, toxin, antitoxin, vaccine, blood, blood component or
derivative, allergenic product, or analogous product, or arsphenamine
or derivative of arsphenamine (or any other trivalent organic arsenic
compound), applicable to the prevention, treatment, or cure of a
disease or condition of human beings.''
What are the special concerns, if any, related to
determining whether a biological product that is added to food has
previously been licensed under section 351 of the PHS Act?
E. Clinical Investigations
Section 301(ll) prohibits the introduction or delivery for
introduction into interstate commerce of food to which has been added a
``drug'' or a ``biological product'' for which ``substantial clinical
investigations have been instituted'' and for which ``the existence of
such investigations has been made public,'' unless the drug or the
biological product was ``marketed in food * * * before any substantial
clinical investigations involving the drug or the biological product
have been instituted.''
1. What is the likely impact of interpreting ``clinical
investigations'' to refer exclusively to studies in humans?
2. What is the likely impact of interpreting the existence of
substantial clinical investigations of a substance in humans to prevent
the addition of such substance to animal feed, including pet food and
feed ingredients?
3. What factors should FDA consider in deciding whether clinical
investigations of a substance are ``substantial?''
4. What factors should FDA consider in determining whether
substantial clinical investigations ``involv[ed] the drug or the
biological product?''
5. Could this provision operate as a disincentive to conduct
clinical studies of substances intended for use in products to be
marketed as conventional foods or dietary supplements? If so, is there
an approach to implementation that could minimize or eliminate this
disincentive?
6. To the extent that this provision discourages clinical
investigations of substances added to food and the public disclosure of
such investigations, what is the likely impact of this provision on so-
called self-determinations of the general recognition of safety (GRAS)
of substances added to food?
F. Marketed
Under section 301(ll)(1), a food containing an approved drug or a
licensed biological product may be shipped in interstate commerce if
the drug or the biological product was ``marketed in food'' prior to
the approval of the drug, the licensing of the biological product, or
the initiation of substantial clinical investigations of the drug or
biological product. Section 201(ff) contains a similar provision.
Section 201(ff) uses the phrase ``marketed as a dietary supplement or
as a food,'' however, while section 301(ll) uses the phrase ``marketed
in food.'' In the context of section 201(ff), FDA has evaluated whether
a substance has been ``marketed'' within the meaning of that provision
by considering: (1) Whether the substance itself has been sold or
offered for sale, either as a finished product or as an ingredient; (2)
for substances that are not sold separately but are components present
in a marketed product, whether the component itself was marketed to
prospective purchasers through, e.g., labeling or advertising for the
product that made claims about the component or otherwise highlighted
its presence. See Pharmanex v. Shalala, 2001 WL 741419, at *4 & n.5 (D.
Utah March 30, 2001).
1. What would be the likely impact of interpreting the term
``marketed'' the same way in section 301(ll) as in section 201(ff)?
What could be the regulatory significance, if any, of the differing
phrases ``marketed in food'' (section 301(ll)) and ``marketed as a
dietary supplement or as a food'' (section 201(ff))?
2. What could be the significance, if any, of the marketing in food
of an approved drug or a licensed biological product outside the United
States?
3. What factors should be considered the indicia of being
``marketed in food?'' What types of evidence should FDA consider in
deciding whether a substance has been ``marketed in food?''
G. Enhance The Safety of The Food Supply
Section 301(ll)(3) provides an exception to the prohibition of
adding a drug or biological product to a food if use of the drug or
biological product is ``to enhance the safety of the food * * * and not
to have independent biological or therapeutic effects on humans.''
1. What factors should FDA consider in determining whether the use
of a substance in food is to ``enhance the safety of the food'' within
the meaning of section 301(ll)?
2. What would be the likely impact of each of the following
possible interpretations of what kinds of uses ``enhance the safety of
the food?''
The addition of a substance to a food enhances the safety
of the food only if such addition reduces a risk not inherent in the
food itself, such as the risk of microbial or other contamination.
The addition of a substance to a food enhances the safety
of the food if such addition reduces either a risk inherent to the food
itself, such as inherent toxicity or a risk that derives from the
nutritional content of the food (e.g., high saturated fat content), or
a risk not inherent in the food itself, such as the risk of microbial
or other contamination.
[[Page 43940]]
H. Independent biological or therapeutic effects on humans
As noted, section 301(ll)(3) provides an exception to the
prohibition of adding a drug or biological product to a food if use of
the drug or biological product is ``to enhance the safety of the food *
* * and not to have independent biological or therapeutic effects on
humans.''
1. What factors should FDA consider in determining whether the use
of a substance in food is to have a ``biological'' effect on humans?
2. What factors should FDA consider in determining whether the use
of a substance in food is to have a biological effect on humans that is
``independent?''
3. What factors should FDA consider in determining whether the use
of a substance in food is to have a ``therapeutic'' effect on humans?
4. What factors should FDA consider in determining whether the use
of a substance in food is to have a therapeutic impact on humans that
is ``independent?''
I. In the Secretary's Discretion
Section 301(ll)(2) permits the addition of a drug or biological
product to a food ``if the Secretary, in the Secretary's discretion,
has issued a regulation after notice and comment, approving the use * *
* in food.'' As noted, the Secretary has delegated his authority under
the act to the Commissioner of Food and Drugs.
1. What factors should the Commissioner consider in exercising his
discretion under section 301(ll)(2)?
2. What should be the impact, if any, on the exercise of the
Commissioner's discretion where use of the drug or biological product
in food has been the subject of another statutory or administrative
process (e.g., a food contact substance notification that is effective
under section 409(h))?
III. Comments
Interested persons may submit to the Division of Dockets Management
(see ADDRESSES) written or electronic comments regarding this document.
Submit a single copy of electronic comments or two paper copies of any
mailed comments, except that individuals may submit one paper 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
Division of Dockets Management between 9 a.m. and 4 p.m., Monday
through Friday.
Please note that on January 15, 2008, the FDA Division of Dockets
Management Web site transitioned to the Federal Dockets Management
System (FDMS). FDMS is a Government-wide, electronic docket management
system. Electronic comments or submissions will be accepted by FDA only
through FDMS at http://www.regulations.gov.
Dated: July 22, 2008.
Jeffrey Shuren,
Associate Commissioner for Policy and Planning.
[FR Doc. E8-17356 Filed 7-28-08; 8:45 am]
BILLING CODE 4160-01-S