[Federal Register Volume 66, Number 12 (Thursday, January 18, 2001)]
[Proposed Rules]
[Pages 4706-4738]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 01-1046]


-----------------------------------------------------------------------

DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

21 CFR Parts 192 and 592

[Docket No. 00N-1396]
RIN 0910-AC15


Premarket Notice Concerning Bioengineered Foods

AGENCY: Food and Drug Administration, HHS.

ACTION: Proposed rule.

-----------------------------------------------------------------------

SUMMARY: The Food and Drug Administration (FDA) is proposing to require 
the submission to the agency of data and information regarding plant-
derived bioengineered foods that would be consumed by humans or 
animals. FDA is proposing that this submission be made at least 120 
days prior to the commercial distribution of such foods. FDA is taking 
this action to ensure that it has the appropriate amount of information 
about bioengineered foods to help to ensure that all market entry 
decisions by the industry are made consistently and in full compliance 
with the law. The proposed action will permit the agency to assess on 
an ongoing basis whether plant-derived bioengineered foods comply with 
the standards of the Federal Food, Drug, and Cosmetic Act (the act).

DATES: Submit written comments on the proposed rule by April 3, 2001. 
Submit written comments on the information collection provisions by 
February 20, 2001.
    See section XIV of this document for the proposed effective date of 
a final rule based on this document.

ADDRESSES: Submit written comments to the Dockets Management Branch 
(HFA-305), Food and Drug Administration, 5630 Fishers Lane, rm. 1061, 
Rockville, MD 20852. Submit written comments on the information 
collection provisions to the Office of Information and Regulatory 
Affairs, OMB, New Executive Office Bldg., 725 17th St. NW., rm. 10235, 
Washington, DC 20503, Attn: Desk Officer for FDA.

FOR FURTHER INFORMATION CONTACT:
    Regarding human food issues: Linda S. Kahl, Center for Food Safety 
and Applied Nutrition (HFS-206), Food and Drug Administration, 200 C 
St. SW., Washington, DC 20204, 202-418-3101.
    Regarding animal feed issues: William D. Price, Center for 
Veterinary Medicine (CVM) (HFV-200), Food and Drug Administration, 7500 
Standish Pl., Rockville, MD 20855, 301-827-6652.

SUPPLEMENTARY INFORMATION:

Table of Contents

I. Background
    A. The 1992 Policy
    B. Consultations Under the 1992 Policy and the 1996 Procedures
    C. Public Meetings
II. Legal Authority
III. Scope
IV. Definitions
V. Requirement for Premarket Biotechnology Notice
    A. Foods That Are Subject to the Requirement
    B. Origin of Data and Information
    C. Timing
VI. Recommendation for Presubmission Consultation
    A. Presubmission Consultation Program
    B. Public Disclosure
    C. Standard Procedures
VII. Premarket Biotechnology Notice: Administrative Information
    A. Submissions to CFSAN for Use in Human Food, Animal Feed, or 
Both
    B. Paper Copies
    C. Electronic Copies
    D. English Language Translations, Incorporation by Reference, 
and Available Guidance Documents
    E. Opportunity to Withdraw
VIII. Premarket Biotechnology Notice: Required Parts
    A. Part I: Letter

[[Page 4707]]

    1. Statements Regarding the Notifier's Responsibility and the 
Balanced Nature of the Notice
    2. Statements Regarding the Availability of Data and Information 
for FDA's Review
    3. Statement Regarding Public Disclosure
    B. Part II: Synopsis
    C. Part III: Status at Other Federal Agencies and Foreign 
Governments
    D. Part IV: Method of Development
    E. Part V: Antibiotic Resistance
    F. Part VI: Substances in the Food
    1. Covered Substances
    2. Identity, Function, Level, and Dietary Exposure
    3. Allergenicity
    4. Other Safety Issues
    G. Part VII: Data and Information About the Food
    1. Comparable Food
    2. Historic Uses of the Comparable Food
    3. Comparing the Composition and Characteristics of the 
Bioengineered Food to That of Comparable Food
    4. Other Relevant Information
    5. Narrative
IX. Agency Administration of a Premarket Biotechnology Notice
    A. Filing Decision
    B. Acknowledgment Letter
    C. Response Letter
    1. General Categories for FDA's Response
    a. Letter That Extends FDA's Evaluation
    b. Letter That the Notice Does Not Provide a Basis
    c. Letter That FDA Has No Questions
    d. Letter That a Notifier Has Withdrawn the Notice
    2. Status of the Bioengineered Food at EPA
X. Public Disclosure
    A. Existence of the Notice
    B. Content of the Notice
    C. Disclosure of FDA's Evaluation of, and Response to, a Notice
XI. Proposed Regulations Regarding Bioengineered Foods That Would Be 
Used in Animal Feed
XII. Paperwork Reduction Act
    A. Hourly Burden to Prepare a Report (Proposed Sec. 192.20(a) 
through (b)(1) and Sec. 192.25
    B. Hourly Reporting Burden Associated With Confidential 
Information in a Report (Proposed Sec. 192.20(b)(2)(i) and 
(b)(2)(ii)
    C. Hourly Reporting Burden Associated With Electronic Copies of 
the Report (Proposed Sec. 192.20(c)(1) and (c)(2)
    D. Hourly Reporting Burden Associated With English Language 
Translations, Authorization to Incorporate Information by Reference, 
and Withdrawal (Proposed Sec. 192.20(d), (e), and (g)
    E. Hourly Reporting Burden Associated With a Voluntary 
Presubmission Consultation Program (Proposed Sec. 192.10(e) through 
(g), (h)(2), (h)(3)(i), and (h)(3)(ii)
    F. Hourly Recordkeeping Burden (Proposed Sec. 192.25(a)(2)
XIII. Analysis of Economic Impacts
    A. Cost-Benefit Analysis
    B. Background
    1. Benefits
    2. Costs
    C. Regulatory Flexibility Act
    D. Unfunded Mandates Reform Act
XIV. Effective Date
XV. Environmental Impact
XVI. Comments
XVII. References

I. Background

A. The 1992 Policy

    In the Federal Register of May 29, 1992 (57 FR 22984), FDA 
published its ``Statement of Policy: Foods Derived From New Plant 
Varieties'' (the 1992 policy). The 1992 policy clarified the agency's 
interpretation of the application of the act with respect to human 
foods and animal feeds derived from new plant varieties, including 
varieties that are developed using recombinant deoxyribonucleic acid 
(rDNA) technology. This proposal refers to foods derived from plant 
varieties that are developed using in vitro manipulations of DNA 
(generally referred to as rDNA technology) as ``bioengineered foods.''
    The 1992 policy provided guidance to industry on scientific and 
regulatory issues related to plant-derived foods, including 
bioengineered foods. In developing the 1992 policy as it relates to 
bioengineered foods, FDA focused on modifications to foods that were 
likely to result in commercial products and did not attempt to predict 
future changes in foods that could result from technological advances. 
Instead, FDA intended to modify its policy as circumstances warranted 
(57 FR 22984 at 22985).
    In announcing the 1992 policy, FDA invited interested persons to 
submit written comments. Comments received from the scientific 
community generally have supported the scientific guidance articulated 
in the 1992 policy, including the scientific guidance as it relates to 
bioengineered foods. In addition, the views expressed by the members of 
FDA's Food Advisory Committee (Ref. 1) and the joint meeting of FDA's 
Food Advisory Committee and Veterinary Medicine Advisory Committee 
(Ref. 2), generally supported the scientific guidance in the 1992 
policy.
    However, many consumers, a number of public interest groups, and 
some State officials have expressed concern about or opposed the 
regulatory guidance articulated in the 1992 policy, particularly 
regarding the ability of the regulated industry to make market entry 
decisions. Frequently, those comments suggested, as an important 
adjunct to the 1992 policy, that FDA require an administrative process, 
such as premarket notification, to ensure that the agency remains aware 
of new bioengineered foods entering commercial distribution.\1\
---------------------------------------------------------------------------

    \1\ This document defines ``commercial distribution'' as the 
introduction, or delivery for introduction, into interstate commerce 
for sale or exchange for consumption in any form by humans or other 
animals.
---------------------------------------------------------------------------

    FDA is confident that the guidance articulated in the 1992 policy 
adequately addressed both the scientific and regulatory issues raised 
by the products that were approaching commercialization in 1992. FDA is 
aware, however, that rDNA technology continues to evolve and that it is 
not possible for the agency to anticipate all of the novel scientific 
and regulatory issues that may arise as the number and types of foods 
developed using this technology expands. As discussed more fully below, 
this proposed rule would modify the regulatory guidance laid out in the 
1992 policy by requiring the submission to the agency of data and 
information regarding plant-derived bioengineered foods at least 120 
days prior to the commercial distribution of such foods.

B. Consultations Under the 1992 Policy and the 1996 Procedures

    In the 1992 policy, FDA explained that, under the act, developers 
of new foods have a responsibility to ensure that the foods they offer 
to consumers are safe and in compliance with all requirements of the 
act (57 FR 22984 at 22985). In light of this responsibility, FDA has 
long regarded it to be a prudent practice for producers who use new 
technologies in the manufacture or development of foods and food 
ingredients to work cooperatively with FDA to ensure that the products 
of these new technologies are safe and comply with all applicable legal 
requirements (57 FR 22984 at 22991). Historically, the food industry 
generally has initiated consultation with FDA during the pioneer stages 
of a new technology, even if there is no legal obligation to do so. 
These consultations have served to make FDA aware of foods and food 
ingredients before these products are distributed commercially, and 
have provided FDA with the information necessary to address any 
questions regarding the safety, labeling, or regulatory status of the 
food or food ingredient. As such, these consultations have provided 
assistance to both industry and the agency in exercising their mutual 
responsibilities under the act.
    In the 1992 policy, FDA noted that the agency expected this 
practice of consultation to continue with respect to bioengineered 
foods (57 FR 22984 at 22991). One early example of such a

[[Page 4708]]

consultation involved FLAVR SAVR<SUP>TM</SUP> tomatoes.\2\ In 
developing FLAVR SAV<SUP>TM</SUP> tomatoes, Calgene used rDNA 
technology to introduce an antisense polygalacturonase gene, which was 
derived from tomatoes, and the kanamycin resistance gene (the kan 
<SUP>r</SUP> gene), which encodes the enzyme aminoglycoside-3'-
phosphotransferase II (APH(3')II). The enzyme APH(3')II confers 
resistance to the clinically used antibiotics kanamycin and neomycin in 
the selection of new plant varieties developed using rDNA technology. 
The use of APH(3')II raised several issues that had not previously been 
evaluated by the agency in the context of food safety. The initial 
consultation between the agency and Calgene about the intended use of 
APH(3')II, which in this instance resulted in the filing and approval 
of a food additive petition (59 FR 26700, May 23, 1994), was an 
effective mechanism to fully explore and resolve these issues.
---------------------------------------------------------------------------

    \2\ This consultation was concluded in May 1994 (59 FR 26647 at 
26700, May 23, 1994).
---------------------------------------------------------------------------

    The resolution of these and other scientific issues entailed the 
use of nontraditional approaches to the evaluation of food safety. For 
example, traditional evaluation of the safety of a food additive 
frequently includes toxicological tests conducted in accordance with 
the principles outlined in the agency's ``Toxicological Principles for 
the Safety Assessment of Direct Food Additives and Color Additives Used 
in Food'' (Redbook (Ref. 3)).\3\ In addition to guidance on when 
certain tests may be appropriate, the Redbook includes specific 
recommendations on the protocols for conducting such tests.
---------------------------------------------------------------------------

    \3\ In 1993, the Center for Food Safety and Applied Nutrition 
(CFSAN) released a revised Redbook for public comment (58 FR 16536, 
March 29, 1993). Following its evaluation of comments on each draft 
chapter of the Redbook, CFSAN is making revised chapters available 
on its Internet site (Ref. 4).
---------------------------------------------------------------------------

    In contrast, issues raised during the consultations on APH(3')II 
and the FLAVR SAVR<SUP>TM</SUP> tomato required evaluation of data 
generated using procedures that had only rarely been used in the 
evaluation of food safety. For example, Calgene used ``Southern blots'' 
to determine which DNA sequences had been transferred to FLAVR 
SAVR<SUP>TM</SUP> tomatoes, ``Northern blots'' to demonstrate the 
intended technical effect in FLAVR SAVR<SUP>TM</SUP> tomatoes, and 
``Western blots'' to determine the amount of APH(3')II present in FLAVR 
SAVR<SUP>TM</SUP> tomatoes. The use of nontraditional strategies in the 
evaluation of food safety likely will become the norm as the use of 
rDNA technology expands, and further consultations between industry and 
the agency would foster the identification and design of reasonable 
test procedures to evaluate the composition and safety of whole foods.
    Consultations are an appropriate forum for industry and the agency 
to address proactively issues that are relevant to bioengineered foods, 
and developers have actively consulted with FDA about their products 
since the issuance of the 1992 policy. In June 1996, FDA provided 
guidance to industry on procedures for these consultations (the 1996 
procedures (Ref. 5)).\4\ Under that process, a developer who intends to 
commercialize a bioengineered food meets with the agency to identify 
and discuss relevant safety, nutritional, or other regulatory issues 
regarding the bioengineered food prior to marketing it. Depending on 
the experience the agency and the developer have with the kind of 
modification being considered, a developer may initiate such a 
consultation early or late in the development of the food. When the 
developer believes that it has accumulated adequate data or information 
to address any issues raised during the consultation, the developer 
begins the ``final consultation'' by submitting to FDA a summary of its 
scientific and regulatory assessment of the food. To date, the agency 
has completed its evaluation of data or other information from more 
than 45 such consultations (Ref. 6). FDA believes that, to date, all 
developers of bioengineered foods commercially marketed in the United 
States have consulted with the agency prior to marketing the food.
---------------------------------------------------------------------------

    \4\ In October 1997, FDA made administrative revisions to these 
procedures to reflect reorganizations within the Office of Premarket 
Approval, CFSAN, and the Center for Veterinary Medicine (CVM). In 
this document, FDA refers to these procedures as ``the 1996 
procedures'' to reflect the year that the agency made them 
available.
---------------------------------------------------------------------------

    FDA continues to believe that the consultation process is 
appropriate for bioengineered foods. Accordingly, this proposed 
rulemaking includes FDA's recommendation that developers consult with 
the agency to identify and discuss relevant safety, nutritional, or 
other regulatory issues regarding a bioengineered food (see proposed 
Sec. 192.10 and section VI of this document).

C. Public Meetings

    In 1999, FDA announced that the agency would hold three public 
meetings, each in a different region of the United States (64 FR 57470, 
October 25, 1999). The purpose of those meetings was for the agency to 
share its current approach and experience over the past 5 years 
regarding bioengineered foods, to solicit views on whether FDA's 
policies or procedures should be modified, and to gather information to 
be used to assess the most appropriate means of providing information 
to the public about bioengineered products in the food supply. In the 
notice announcing the public meetings (64 FR 57470), FDA requested 
comments on specific questions regarding bioengineered foods. As a 
result of those meetings and the request for comments, the agency 
subsequently received more than 35,000 written comments about its 
policy regarding bioengineered foods.
    At those meetings, and in the comments, FDA heard three messages 
very clearly. First, there does not appear to be any new scientific 
information that raises questions about the safety of bioengineered 
foods currently being marketed. Second, some of the public is concerned 
about FDA's existing guidance and regulatory approach to overseeing the 
safety of these products. These concerns include whether FDA's guidance 
and regulatory approach will be adequate for future developments and 
whether firms will continue to inform FDA about new bioengineered foods 
under the present program. In addition, there was a concern that the 
current regulatory process lacks transparency (e.g., because FDA 
discloses each consultation about a bioengineered food only at the end 
of the process). Third, there are very strongly held but divergent 
views as to whether bioengineered foods should bear special labeling. 
However, there was general agreement that providing more information to 
consumers about bioengineered foods would be useful \5\ (Ref. 8).
---------------------------------------------------------------------------

    \5\ In May 2000, FDA announced that it intended to issue for 
public comment draft labeling guidance to aid manufacturers who wish 
to voluntarily label their products as made with or without the use 
of bioengineering or bioengineered ingredients (Ref. 7). The 
development of that draft guidance is outside the scope of this 
document.
---------------------------------------------------------------------------

II. Legal Authority

    FDA is responsible for ensuring that all foods \6\ in the American 
food supply conform to the applicable provisions of the law. The act 
provides FDA with broad authority to regulate the safety and 
wholesomeness of food. In particular, the act prohibits the 
adulteration of food under section 402 of the act (21 U.S.C. 342) and 
the misbranding of food under section 403

[[Page 4709]]

of the act (21 U.S.C. 343). The act also requires that all food 
additives (as defined by section 201(s) of the act (21 U.S.C. 321(s))) 
be approved by FDA before they are marketed (sections 409 and 402 of 
the act (21 U.S.C. 348(a) and 342(a)(2)(C))). FDA is authorized to seek 
sanctions against foods that do not adhere to the act's standards, 
through seizure of foods that violate the act under section 304 of the 
act (21 U.S.C. 334); the agency is also authorized to seek an 
injunction against, or criminal prosecution of, those responsible for 
introducing such foods into commerce under sections 302 and 303 of the 
act (21 U.S.C. 332 and 333).
---------------------------------------------------------------------------

    \6\ There are certain exceptions to this jurisdiction pertaining 
to meat, poultry, and egg products that are not relevant to this 
rulemaking.
---------------------------------------------------------------------------

    All plant breeding techniques have the potential to alter food 
source crops in ways relevant to the legal status of food derived from 
such crops. However, rDNA technology greatly facilitates, relative to 
traditional breeding techniques, both the introduction of specific new 
substances into foods and the directed modification of the composition 
of foods. This is in part because the technology expands the range of 
sources of new substances that can be introduced into plants, relative 
to those that can be introduced with traditional techniques, due 
principally to rDNA technology's ability to permit the transfer to a 
food crop of genetic material from virtually any organism. Similarly, 
at the present time, information related to the genomes of many 
organisms is rapidly expanding, with the result that newly identified 
genes are now available to breeders. In addition, rDNA technology 
increases the speed by which traits can be introduced into food crops, 
by allowing the introduction of specific, well-characterized genetic 
material and by reducing the need for backcrossing to remove 
undesirable traits. Given the efficiencies of rDNA techniques, the 
advances in these techniques, and the rapidly expanding information 
related to genomes, FDA expects that these techniques are likely to be 
utilized to an increasingly greater extent by plant breeders and that 
the products of this technology are likely in some cases to present 
more complex safety and regulatory issues than seen to date.
    Alterations in food source plants accomplished using rDNA 
technology, with resulting changes in the foods derived from such 
plants, can present a range of regulatory issues (57 FR 22984 to 
23005). For example, such alterations may present questions as to the 
food additive status of the substances introduced into the food as a 
result of the genetic transformation. As noted, bioengineering permits 
the introduction into food of substances from any source, and the 
number and types of genes available for use in rDNA technology are 
rapidly increasing. Thus, increasingly, substances may be introduced 
into food using rDNA techniques that cannot be introduced by 
traditional breeding. FDA noted in the 1992 policy that a nonpesticidal 
substance introduced into food by way of breeding is a food additive if 
the substance is not generally recognized as safe (GRAS) within the 
meaning of 21 U.S.C. 321(s). Because of the greater range of sources of 
substances that can be introduced into plants via rDNA technology, 
there is a greater likelihood that some of the new substances will be 
significantly different from substances that have a history of safe use 
in food or may otherwise not satisfy the GRAS standard in section 
201(s) of the act(s). Thus, there is a greater potential for foods 
developed using rDNA technology to contain substances that are food 
additives.
    The agency reiterates its view, as stated in the 1992 policy (57 FR 
22990), that transferred genetic material can be presumed to be GRAS. 
Likewise, FDA is not altering its view, as set forth in the 1992 
policy, that there is unlikely to be a safety question sufficient to 
question the presumed GRAS status of the proteins (typically enzymes) 
produced from the transferred genetic material, or of substances 
produced by the action of the introduced enzymes (such as 
carbohydrates, fats, and oils), when these proteins or other substances 
do not differ significantly from other substances commonly found in 
food and are already present at generally comparable or greater levels 
in currently consumed foods. However, FDA recognizes that because 
breeders utilizing rDNA technology can introduce genetic material from 
a much wider range of sources than previously possible, there is a 
greater likelihood that the modified food will contain substances that 
are significantly different from, or are present in food at a 
significantly higher level than, counterpart substances historically 
consumed in food. In such circumstances, the new substances may not be 
GRAS and may require regulation as food additives (57 FR 22990).
    To date, FDA has not seen multiple examples of food additive 
substances introduced into food using rDNA technology. However, the 
agency recognizes that the potential for introducing such substances is 
real. There are, for example, certain plant-derived proteins that have 
a sweetening effect but whose biochemical function is not known.\7\ In 
addition, they are found in plants that have not been used for food. 
Thus, in contrast to other proteins introduced into foods by genetic 
engineering, which have been presumed GRAS, there is little or no 
apparent basis for a GRAS presumption for such substances. Genes 
encoding the protein sweetener could be introduced into a fruit to 
enhance sweetness. In such circumstances, FDA should be made aware of 
the intended marketing of the modified food and have access to relevant 
information to evaluate whether the protein sweetener is a food 
additive within the act's definition under section 201(s) of the act. 
If the protein sweetener is a food additive, premarket approval of the 
substance would be required under section 409 of the act before the 
altered food could be lawfully marketed.
---------------------------------------------------------------------------

    \7\ The proteins apparently do not make the plants more 
attractive to insects or animals, and thus would not likely function 
as natural sweeteners in plants in the wild.
---------------------------------------------------------------------------

    Another potential consequence of transferring genetic material from 
one source into another is the possibility of introducing a food 
allergen that would not be expected to be in a particular food, a 
change that would be relevant to the legal status of such food. This is 
because genes code for proteins, and virtually all allergens are 
proteins (although only a small subset of proteins are allergens). 
Thus, by increasing the range of potential proteins that can be 
introduced into food over that possible by traditional breeding, there 
is an increased potential for introducing an allergen into a food 
developed using rDNA technology. Also, rDNA technology can be used to 
express proteins at higher concentrations than they would otherwise be 
expressed; these higher concentrations may increase the potential for 
such proteins to be allergenic.
    One implication of being able to transfer genes between unrelated 
plants using rDNA techniques is that it is possible to transfer genes 
from one food plant to another quite unrelated food plant, thereby 
allowing the potential transfer of an allergen from the first plant to 
the second. In such a case, food from the bioengineered plant could 
have an allergenic characteristic completely different from that of its 
conventional counterpart. Such a change would not be evident to the 
consumer. For example, a gene from a Brazil nut plant was introduced 
into a soy plant to improve the protein content of soy beans for use in 
animal feed. The seed was never commercialized, however, because when 
the company tested the

[[Page 4710]]

soy beans for allergenicity, they found that people allergic to Brazil 
nuts were also allergic to the bioengineered soy (Refs. 9 and 10). 
Given the potential consequences to sensitive consumers of eating soy 
products containing a Brazil nut allergen, such a food would likely be 
considered misbranded within the meaning of sections 201(n) and 
403(a)(1) of the act, unless the presence of the new allergen were 
disclosed to consumers.
    Further, in certain circumstances, labeling may not be adequate or 
practical to ensure that consumers are aware of the presence of 
unexpected allergens. FDA would likely consider such food containing an 
unexpected allergen to be adulterated within the meaning of section 
402(a)(1) of the act because the unexpected allergen rendered the food 
possibly injurious to health. With alterations of this type, FDA should 
be made aware of the modification and have an opportunity to assess 
whether and how the food could legally be marketed. Specifically, FDA 
should have the opportunity to consider whether any labeling proposed 
by the developer would ensure that the engineered food is not 
misbranded within the meaning of sections 201(n) and 403(a)(1) of the 
act, and whether, even with labeling, the food would be adulterated 
because it may be injurious to health within the meaning of section 
402(a)(1) of the act.
    Compositional changes in foods created through breeding may also 
present regulatory status issues. Although traditional breeding 
techniques can be used to alter significantly the compositional 
characteristics of food, rDNA technology enhances that ability because 
rDNA technology enables breeders to make targeted changes in plant 
components such as proteins and other constituents. For example, rDNA 
techniques would facilitate a breeder's ability to modify a soy plant 
so that the composition of oil derived from the plant would more 
closely resemble that of a tropical oil than that of conventional soy 
oil. In these circumstances, the name ``soy oil'' would likely not be 
suitable for the oil derived from the altered soy plant because the 
composition of the new oil is significantly different from what is 
customarily understood to be ``soy oil''. Thus, a new common or usual 
name would likely be required for this new oil to ensure that the oil 
is not misbranded under section 403(i)(1) of the act. FDA should be 
made aware of compositional changes of this type so that the agency may 
consider whether a new common or usual name is required and, if so, 
what that new name should be.
    Additionally, rDNA technology has recently begun to be used to 
introduce multiple genes to generate new metabolic pathways (Ref. 11). 
New metabolic pathways are intended to result in the synthesis of 
substances not normally present in the host plant. Such modifications 
may alter the composition of the food in a significant manner that may 
raise nutritional or safety issues or that would require use of a new 
common or usual name.
    In addition to enabling breeders to introduce desired new 
characteristics into foods, all breeding methods used to develop new 
plant varieties have a potential for unintentionally introducing 
undesired new characteristics into foods (57 FR 22986). Broadly 
speaking, a breeding method's potential for introducing unintended 
changes to the characteristics of a food results either from bringing 
into a food plant extraneous genetic material encoding trait(s) 
additional to the desired trait(s), or from introducing mutations (such 
as deletions, amplifications, insertions, rearrangements, or DNA base-
pair changes) into the plant's native genetic material that alter some 
characteristic(s) of the food.
    The most commonly used breeding method is a ``narrow cross,'' which 
is hybridization between varieties of the same species. Hybridization 
between related species or genera that cannot be cross-fertilized is a 
``wide cross.'' Wide crosses are useful for expanding the range of 
genetic source material that can be introduced into food crops, but are 
performed relatively infrequently because of technical and logistical 
difficulties. Both wide and narrow crosses will introduce into plants 
extraneous genetic material along with the genetic material encoding 
the desired traits. Breeders then attempt to remove any undesired 
traits through extensive backcrossing.
    Plant breeders also use mutagenic techniques to modify plants. 
These techniques include random mutagenesis using a mutagenic agent and 
somaclonal variation. (Somaclonal variation refers to the process of 
growing a plant up from tissue culture and observing for phenotypic 
changes, which are often due to chromosomal rearrangements or other 
mutations.) Both techniques can introduce undesirable mutations along 
with possible desirable mutations. As with hybridization, breeders 
perform backcrosses to eliminate any undesirable traits. Cell fusion 
poses similar issues to those posed by wide crosses (because it 
generally is performed between cells of different species of plants) 
and posed by somaclonal variation (because it involves growing a plant 
up from tissue culture).
    Recombinant DNA technology greatly reduces the likelihood of 
introducing extraneous genetic material, as compared with 
hybridization, because it enables breeders to introduce only the gene 
or genes of interest, with little or no extraneous deoxyribonucleic 
acid (DNA). However, it shares with mutagenesis techniques a potential 
for introducing unintended effects through mutations. In part, this is 
because rDNA technology involves growing plants from tissue culture, 
which can exhibit somaclonal variation, and, more significantly, 
because breeders using this technology generally cannot control the 
location in the plant genome at which genetic material will insert when 
introduced into a plant. Thus, with rDNA technology, the introduced 
genetic segment may insert into a genetically active chromosomal 
location. Such insertion may disrupt or inactivate an important gene or 
a regulatory sequence that affects the expression of one or several 
genes, thereby potentially affecting adversely the safety of the food 
or raising other regulatory issues. Such an occurrence is referred to 
as an insertional mutation.
    FDA believes that in the future, plant breeders will increasingly 
use rDNA techniques to achieve more complicated compositional changes 
to food, sometimes introducing multiple genes residing on multiple 
vectors to generate new metabolic pathways. FDA expects that with the 
increased introduction of multiple genes, unintended effects may become 
more common. For example, rice modified to express pro-vitamin A was 
shown to exhibit increased concentrations of xanthophylls (Ref. 11), 
and rice modified to reduce the concentration of a specific protein was 
found to exhibit an increased concentration of prolamine (Ref. 12).
    FDA believes that the use of rDNA techniques in plant breeding may 
lead to unintended changes in foods that raise adulteration or 
misbranding questions. These unintended changes may cause a food to be 
adulterated because the food may be rendered injurious to health within 
the meaning of section 402(a)(1) of the act, or, in the absence of a 
new common or usual name, cause the food to be misbranded under section 
403(i)(1) of the act. Because of its role in ensuring the safety of the 
U.S. food supply, FDA needs to be aware of the modifications to food 
source plants from the application of rDNA technology and any 
unintended effects in food that result so that the agency can evaluate 
whether the foods

[[Page 4711]]

from such plants are adulterated or misbranded.
    Because some rDNA-induced unintended changes are specific to a 
transformational event (e.g., those resulting from insertional 
mutagenesis), FDA believes that it needs to be provided with 
information about foods from all separate transformational events, even 
when the agency has been provided with information about foods from 
rDNA-modified plants with the same intended new trait and has had no 
questions about such foods. Similarly, the agency believes that it 
needs to be provided with information about foods from rDNA-modified 
plants whose intended change is the introduction of a pesticidal 
protein subject to oversight by the Environmental Protection Agency 
(EPA) rather than by FDA, because the transformational event that is 
used to introduce the pesticidal trait may also cause unintended 
changes to the food that would raise adulteration or misbranding 
questions subject to FDA jurisdiction.
    In contrast, the agency does not believe that it needs to receive 
information about foods from plants derived through narrow crosses 
(including narrow crosses between different rDNA-modified lines). 
Narrow crosses, because they generally are performed between varieties 
that are themselves used in food or are very closely related to 
varieties used in food, are unlikely to introduce extraneous DNA that 
encodes traits that have not been in food before. In addition, plant 
lines used for narrow crosses generally have been subject to extensive 
backcrossing and field testing to ensure genetic stability (including 
lack of any active transposons that could cause insertional 
mutagenesis). Finally, because the plant lines are closely related to 
each other, crosses between them will involve homologous recombination 
and thus are unlikely to be subject to insertional mutagenesis. 
Therefore, narrow crosses are unlikely to result in unintended changes 
to foods that raise safety or other regulatory questions.
    The agency recognizes that unintended changes associated with other 
non-rDNA breeding methods may pose regulatory questions similar to 
those posed by rDNA methods. For example, wide crosses, especially 
between a food plant variety and an undomesticated nonfood plant 
variety, have much greater potential than do narrow crosses for 
introducing unintended traits that may alter the safety of the food; 
undomesticated plants frequently produce toxins at levels unsafe for 
human consumption, and may also produce substances not found in food. 
The agency has not found it necessary to assess routinely the safety of 
foods derived from such breeding methods, because over the last 50 to 
60 years that some of these techniques have been used in plant 
breeding, breeders have used well-established practices successfully to 
identify and eliminate, prior to commercial use, plants that exhibit 
unexpected adverse traits. The agency is not aware of a basis for 
additional FDA oversight of foods derived from plants modified by such 
techniques, given that there has not been such a need in the past and 
that there do not appear to be any significant changes in breeders' use 
of such techniques that would warrant new FDA oversight. Rather, 
because of the technical advantages of rDNA methods over these other 
techniques, FDA anticipates that, in the future, breeders will likely 
use non-rDNA methods less frequently to introduce new characteristics 
into food plants as they increasingly utilize rDNA techniques. 
Likewise, despite the similar potential for unintended effects, FDA 
believes that declining to propose a requirement that the agency be 
notified about the commercialization of food source plants transformed 
using techniques other than rDNA is consistent with its current 
conclusion that, unexpected effects aside, rDNA techniques have a 
greater potential, relative to conventional methods of breeding, to 
result in the development of foods that present legal status questions. 
The agency therefore is not proposing to include foods from crops 
modified by methods other than rDNA techniques within the scope of this 
proposed notification rule. The agency requests comment as to whether 
it should include foods from crops developed by wide crosses or other 
breeding methods in the scope of any final rule based upon this 
proposal.
    FDA recognizes that whether there is a change in the legal status 
of a food resulting from a particular rDNA modification depends almost 
entirely on the nature of the modification, and that not every 
modification accomplished with rDNA techniques will alter the legal 
status of the food. In other words, many modifications will result in a 
food that does not contain an unapproved food additive, does not 
contain an unexpected allergen, and does not differ significantly in 
its composition compared with its traditional counterpart or otherwise 
require special labeling. For this reason, FDA is neither proposing to 
require premarket approval for all foods developed using rDNA 
technology nor is the agency proposing an across-the-board requirement 
that all such foods bear special labeling.
    There is substantial basis to conclude, however, that there is 
greater potential for breeders, using rDNA technology, to develop and 
commercialize foods that are more likely to present legal status issues 
and thus require greater FDA scrutiny than those developed using 
traditional or other breeding techniques. It was in part for this 
reason that, in 1994, the agency initiated a consultation process. 
Since that time, developers have actively consulted with FDA regarding 
their new plant varieties; under this process, the agency has completed 
its evaluation of data and other information from some 45 
consultations.
    As noted, FDA believes that, to date, the developer of each rDNA 
variety commercially marketed in the United States has consulted with 
the agency prior to marketing food from the new variety. But these 
products represent only a small fraction of the potential products of 
rDNA technology.\8\ Additionally, in general, the introduced traits 
have been agronomic in nature (i.e., directed at the characteristics of 
the plant and not at the characteristics of the food produced by the 
plant). However, this picture is rapidly changing. The current list, 
which is provided by the Animal and Plant Health Inspection Service 
(APHIS) in the U. S. Department of Agriculture (USDA), of field tests 
of plants being developed using rDNA technology shows that the plants 
under development have a broader variety of introduced traits (Ref. 
13). Additionally, that list shows that many such traits are not simply 
agronomic, but are intended to modify the food itself, and thus would 
be more likely than in the past to raise regulatory issues falling 
under FDA's purview.\9\ Finally, as noted previously, FDA believes 
that, given the efficiencies of rDNA techniques, the advances in these 
techniques, and the rapidly expanding information related to genomes, 
these techniques are likely

[[Page 4712]]

to be utilized by plant breeders to an increasingly greater extent.
---------------------------------------------------------------------------

    \8\ For example, in the 45 consultations completed under the 
1992 policy, only 11 different commodities are represented, 
including 12 consultations on corn, 7 on canola, 6 on tomatoes, 5 on 
cotton, and 4 on potatoes. Moreover, the 45 consultations do not 
represent 45 separate types of modifications; rather, these 45 
consultations represent only 9 general types of modifications. These 
modifications were herbicide resistance, insect and virus 
resistance, delayed ripening or softening, male sterility or 
fertility restorer, high phosphorus availability, and modified oil.
    \9\ These include modifications for altered protein quality, 
increased carotenoid content, increased fruit solids, altered fiber 
quality, and increased fruit sweetness, among others.
---------------------------------------------------------------------------

    The confluence of the increasingly broader use of rDNA techniques 
to develop foods for human and animal use and the globalization of the 
world's food supply also suggest that FDA needs to be aware of the 
various foods developed using rDNA technology. Currently, approximately 
45 percent of the United States' plant-derived food is imported, and 
that percentage continues to increase. The agency expects that rDNA 
techniques may, over time, be used increasingly by plant breeders and 
developers in countries that export foods to this country. In such 
circumstances, the accuracy of FDA's knowledge about the presence in 
the U.S. food supply of foods developed using rDNA techniques is likely 
to decrease. In addition, the awareness of particular food allergies is 
not uniform throughout the world because the diets of some populations 
do not contain sufficiently large amounts of a food such that the 
allergic potential has been demonstrated; in these circumstances, it is 
particularly important that FDA be aware of imported foods modified 
using rDNA techniques that may unexpectedly contain a substance that is 
an allergen.
    For all these reasons, FDA believes that the food products of rDNA 
technology are appropriately made subject to greater regulatory 
scrutiny by FDA in the form of enhanced agency awareness of all such 
foods intended for commercial distribution. This increased agency 
awareness will ensure that at this stage of this continuously evolving 
technology, all market entry decisions about new bioengineered foods, 
including those intended for import into the United States, are made 
consistently and in full compliance with the law. Similarly, in order 
for the agency to evaluate fully and consistently the possible 
regulatory consequences of the alterations made possible using rDNA 
technology, FDA must be made aware of the bioengineered foods entering 
commercial distribution.
    Section 701(a) of the act (21 U.S.C. 371(a)) authorizes the 
Secretary of the Department of Health and Human Services (the 
Secretary) to issue regulations for the efficient enforcement of the 
act; under section 903(d)(2) of the act (21 U.S.C. 393(d)(2), the 
Secretary is responsible for executing the act, including section 
701(a), through the Commissioner of Food and Drugs. The authority under 
section 701(a) of the act to issue regulations under the act extends to 
both regulations that supplement a specific statutory mandate as well 
as regulations that are justified by the statutory scheme as a whole. 
(See National Confectioner's Association v. Califano, 569 F.2d 690, 693 
(D.C. Cir. 1978), citing Toilet Goods Association v. Gardner, 387 U.S. 
158, 163 (1967).) In assessing a regulation issued under section 
701(a), it is important to consider both the statutory purpose as well 
as the practical aspects of the situation, including the possible 
enforcement problems that may be encountered by FDA. (See National 
Confectioner's Association v. Califano, 569 F.2d 690, 693 (D.C. Cir. 
1978), citing Toilet Goods Association v. Gardner, 387 U.S. 158, 163 
(1967).)
    To ensure that FDA has the maximum amount of information about 
foods from bioengineered plants, the agency has tentatively concluded 
that, prior to initiation of commercial distribution in the United 
States of a bioengineered food, FDA must be notified of the intent to 
market such food, including foods intended for import into the United 
States. Notification will ensure that the agency is aware of all 
bioengineered foods entering commercial distribution that are subject 
to FDA's jurisdiction and will help to ensure that all market entry 
decisions by the industry are made consistently and in full compliance 
with the law. This will permit the agency to assess on an ongoing basis 
whether foods developed using rDNA technology comply with the standards 
of the act. FDA believes that it is essential that all those developing 
and marketing bioengineered foods participate fully and completely in 
the proposed notification program. Therefore, the agency is proposing 
that the notification program that is described in this document be 
mandatory.
    Accordingly, for the reasons set forth above concerning the special 
circumstances of bioengineered foods, to enforce the act efficiently, 
and in particular, to administer efficiently the act's various 
provisions that relate to food as such provisions apply to 
bioengineered food, including section 301 of the act (21 U.S.C. 331) 
and sections 402, 403, and 409 of the act, FDA is proposing regulations 
to require that the agency be notified at least 120 days prior to the 
initiation of commercial distribution in the United States of a 
bioengineered food. The elements of FDA's proposed program are 
discussed in detail below.

III. Scope

    FDA is proposing to require the submission to the agency of data 
and information regarding plant-derived bioengineered foods that would 
be consumed by humans or animals. FDA's proposal also includes a 
recommendation that prospective notifiers participate in a 
presubmission consultation program. The regulations regarding 
bioengineered foods that would be consumed by humans would be codified 
in new part 192. The regulations regarding bioengineered foods that 
would be consumed by animals would be codified in new part 592. The 
proposed regulations regarding bioengineered foods that would be 
consumed by animals parallel the proposed regulations regarding 
bioengineered foods that would be consumed by humans. For ease of 
discussion, in this proposed rule, FDA describes each of the 
regulations that would be codified in part 192, without describing the 
parallel regulations in part 592. Following this discussion, FDA 
describes areas of importance in the proposed animal feed regulations 
(section XI of this document).

IV. Definitions

    FDA is proposing to codify five definitions that are associated 
with the proposed notification program (proposed Sec. 192.1). These 
terms are bioengineered food, commercial distribution, notifier, 
premarket biotechnology notice (PBN or notice), and transformation 
event. FDA invites comments on these proposed definitions. FDA is 
particularly interested in comments on the proposed definitions of 
bioengineered food and transformation event. Specifically, FDA is 
requesting comment on whether these proposed definitions are consistent 
with the agency's intent (described in section V of this document) that 
the proposed notification program apply to a particular subset of 
plant-derived foods. Such comments may result in a modification to the 
proposed definitions.
    Under the proposed definitions, a required PBN may be submitted by 
any person who is responsible for the development, distribution, 
importation, or sale of a bioengineered food. Based on the agency's 
experience, FDA expects that it ordinarily will be the seed developers 
and purveyors who notify the agency about a bioengineered food.

V. Requirement for Premarket Biotechnology Notice

    FDA is proposing to require a submission to the agency of data and 
information regarding a plant-derived bioengineered food at least 120 
days prior to the commercial distribution of the food (proposed 
Sec. 192.5). The proposed regulation would include a bioengineered food 
derived from a new

[[Page 4713]]

plant variety modified to contain a pesticidal substance, and would 
exclude a bioengineered food that meets three specified criteria. The 
rationale for this proposed notification requirement is discussed in 
section II of this document. FDA specifically requests comment on the 
scope of the proposed notification requirement and on the proposed 
conditions for exclusion from the notification requirement. Such 
comments may result in a modification to the proposed regulation.

A. Foods That Are Subject to the Requirement

    FDA is proposing that the notification requirement apply to a 
bioengineered food derived from a new plant variety modified to contain 
a pesticidal substance (proposed Sec. 192.2(a)). Under the Federal 
Insecticide, Fungicide, and Rodenticide Act (FIFRA) (7 U.S.C. 136 et 
seq.), EPA has authority to regulate all pesticides, regardless of how 
they are made or their mode of action. Under the act, EPA has authority 
to regulate pesticide residues in foods and FDA has authority to 
regulate a nonpesticidal substance that may be introduced into a new 
variety and that is expected to become a component of food. Given this 
statutory framework, both FDA and EPA agree that any food safety 
questions beyond those associated with the pesticide, such as those 
raised by unexpected or unintended compositional changes, are under 
FDA's jurisdiction (57 FR 22984 at 23005). FDA's proposal to include in 
its notification program new plant varieties that contain a pesticidal 
substance will facilitate consultation between EPA and FDA on the 
scientific and regulatory issues that are not within the scope of EPA's 
authority under FIFRA and the act.
    FDA is proposing to exclude from the notification requirement a 
bioengineered food that satisfies three conditions. The first condition 
is that the food derives from a plant line that represents a 
transformation event that has been addressed in a notice previously 
submitted to FDA (proposed Sec. 192.5(a)(1)). Under Sec. 192.5(a)(1), a 
separate notice would be required for distinct plant lines that are 
derived from separate transformed cells, even when those cells were 
transformed during a single transformation procedure. The second 
condition is that the use or application of the bioengineered food has 
been addressed in a notice previously submitted to FDA (proposed 
Sec. 192.5(a)(2)). Under Sec. 192.5(a)(2), a separate notice would be 
required, for example, if herbicide tolerance introduced into a variety 
of sweet corn that is used solely for human food is subsequently 
transferred, using traditional plant-breeding techniques, to a variety 
of field corn that would also be used in food intended for consumption 
by animals. The third condition is that a letter from FDA demonstrates 
that FDA has evaluated the use or application of the bioengineered food 
and has no questions about it (proposed Sec. 192.5(a)(3)). Under 
Sec. 192.5(a)(3), a notice would be required if, for example, a prior 
notice about another use of a bioengineered food is still pending or if 
the agency's response to a prior notice demonstrates that FDA did not 
consider the prior notice as providing a basis to conclude that the 
bioengineered food was in compliance with all applicable requirements 
of the act.
    As mentioned, FDA believes that all developers of bioengineered 
foods that already are commercially marketed in the United States have 
consulted with the agency prior to marketing the food. FDA believes 
that any legal status questions that pertain to the applicable 
bioengineered foods have been identified and resolved through that 
consultation process. Therefore, the notification requirement would not 
extend to bioengineered food obtained from a plant line (or series of 
plant lines) that derives from a particular transformation event, as 
long as both the applicable transformation and the use or application 
of the bioengineered food has been addressed satisfactorily in a 
completed consultation under the voluntary program.
    It is likely that some final consultations received under the 1996 
procedures would still be pending on the date of a final rule based on 
this proposal. The proposed regulations include no specific provisions 
regarding a bioengineered food that is the subject of a pending final 
consultation under the 1996 procedures. FDA specifically requests 
comment on how FDA should administer such submissions. FDA also 
specifically requests comment on whether the process for administering 
a final consultation that is pending on the date of a final rule based 
on this proposal should be included in these regulations. Such comments 
may result in a modification to the proposed regulation.
    FDA specifically requests comment on the scope of proposed 
notification requirement and on the proposed conditions for exclusion 
from the notification requirement. Such comments may result in a 
modification to the proposed regulation.

B. Origin of Data and Information

    FDA is proposing that the data or information that a notifier 
submits to FDA regarding a bioengineered food must be generated from a 
plant line whose derivation can be traced to the transformation event 
that is the subject of the notice and that contains the genetic 
material introduced via the transformation event (proposed 
Sec. 192.5(b)). As a practical matter, the proposed regulation will 
give flexibility to producers while providing the agency with relevant 
information concerning the nature of the bioengineered foods. FDA 
specifically requests comment on this proposed provision. Such comments 
may result in a modification to the proposed regulation.

C. Timing

    FDA is proposing to require that a notifier submit a PBN at least 
120 days before the bioengineered food is marketed (proposed 
Sec. 192.5(c)). The proposed timeframe is consistent with contemporary 
expectations of the Congress for another notification program, the 
notification program for food contact substances (section 409(h) of the 
act).
    FDA believes that it can, in most circumstances, complete its 
evaluation of a PBN within 120 days because, as discussed more fully 
below, FDA is recommending that prospective notifiers participate in a 
presubmission consultation program. The purpose of the presubmission 
consultation program is to enable a prospective notifier to identify 
and address relevant safety, nutritional, or other regulatory issues 
regarding the bioengineered food before submitting a PBN. Given this 
presubmission consultation program, FDA expects that a notifier will 
have sufficient information to prepare a notice that adequately 
addresses all issues and that scientific experts at the agency will be 
familiar with the issues raised by a particular bioengineered food when 
the agency receives the applicable PBN.\10\
---------------------------------------------------------------------------

    \10\ The consultation procedures do not identify a timeframe for 
FDA to complete its evaluation of a final consultation. As of April 
2000, under that program the median time for FDA's response to a 
final consultation was approximately 155 days and the average time 
was approximately 175 days.
---------------------------------------------------------------------------

VI. Recommendation for Presubmission Consultation

    FDA is proposing to include in the regulation a recommendation that 
a prospective notifier consult with the agency, before submitting a 
PBN, to identify and discuss relevant safety, nutritional, or other 
regulatory issues regarding the bioengineered food

[[Page 4714]]

(proposed Sec. 192.10). The proposed recommendation describes 
procedures for requesting consultation and the public disclosure 
provisions that likely would apply to records that FDA maintains about 
the consultation. Under Sec. 192.10(f), a notifier must state his view 
as to whether the fact that he is consulting with FDA, or any or all of 
the data or information that he submits to FDA, is exempt from 
disclosure under the Freedom of Information Act (FOIA) and must explain 
the basis for any such exemption claim. The recommendation to consult 
with FDA derives from the 1992 policy, the 1996 procedures, and FDA's 
experience under the 1996 procedures. FDA discusses the details of this 
proposed recommendation immediately below.
    Using rDNA technology, bioengineered plants such as corn are now 
being developed for non-food uses. Examples of such applications 
include the transfer of genes that encode pharmaceutical proteins, oral 
vaccines, and enzymes that would be used for non-food industrial 
applications. In some cases, such as most of the pharmaceutical 
proteins, the final product would be a highly purified component of the 
plant commodity. In other cases, such as some oral vaccines, the final 
product would be a minimally processed plant commodity. In some cases, 
there may be a potential for a bioengineered plant commodity that is 
not intended for use in food to enter the food supply inadvertently. 
FDA encourages developers of bioengineered plants that are not intended 
for use in food or feed, but that theoretically could enter the food or 
feed supply, to participate in the consultation program described in 
this proposed rule. This participation would ensure that developers 
have given careful consideration to the procedures needed to ensure 
that their products do not inappropriately get into the food supply, 
and are aware of the legal implications if their products do.

A. Presubmission Consultation Program

    FDA is proposing to recommend that a prospective notifier 
participate in a presubmission consultation program (proposed 
Sec. 192.10(a)). Under the program (proposed Sec. 192.10(b)), a 
prospective notifier would write to FDA and ask to consult about a 
bioengineered food. FDA would establish an administrative file for each 
consultation and would meet with a prospective notifier upon request. 
Although FDA may provide written feedback during the consultation, that 
feedback would not release the prospective notifier from the proposed 
requirement to notify FDA about the bioengineered food at least 120 
days before commercialization of the food. The proposed presubmission 
consultation program derives from the 1992 policy, the 1996 procedures, 
and FDA's experience under the 1996 procedures.

B. Public Disclosure

    FDA is proposing to provide information about the availability for 
public disclosure of: (1) The fact that a developer is consulting with 
FDA (proposed Sec. 192.10(c)) and (2) the data or information in the 
file that FDA would establish for a presubmission consultation 
(proposed Sec. 192.10(d)). The regulations would inform all parties of 
the fact that FDA must act in response to a request under FOIA for 
information on presubmission consultations, and must disclose, or 
protect from disclosure, the applicable record(s) in accordance with 
Sec. 20.61 (21 CFR 20.61) (proposed Sec. 192.10(c)(2) and (d)(1)).
    In light of the significant public interest in bioengineered foods 
and in FDA's oversight of these foods, FDA believes that it is 
important for developers to be informed that FOIA may entitle the 
public to know that the developer has provided data or information to 
FDA about a bioengineered food and to receive a copy of those data or 
information. Likewise, FDA believes that it is equally important for 
the public to know that the fact that a developer is consulting with 
FDA may be exempt from disclosure under FOIA and that some or all of 
the data or information that are submitted to FDA during a 
presubmission consultation could be exempt from public disclosure.
    Under FOIA, data or information that are submitted to the Federal 
Government are available for public disclosure unless those data or 
information fall within an established exemption of FOIA. The exemption 
that is most relevant to data or information provided to FDA during a 
presubmission consultation is ``exemption 4,'' which applies to ``trade 
secrets and commercial or financial information obtained from a person 
and privileged or confidential.'' (5 U.S.C. 552(b)(4)). FDA has issued 
regulations implementing exemption 4 of FOIA in Sec. 20.61.
    FDA believes that, in most cases, the fact that a developer is 
consulting with FDA would not constitute confidential commercial 
information. For example, most plants developed using rDNA technology 
are considered ``regulated articles'' under regulations of USDA's APHIS 
(7 CFR part 340), which regulates the introduction of certain 
``genetically engineered'' plants. At some stage of research and 
development of a regulated article, a developer requests from APHIS a 
determination of the article's regulatory status, and, consistent with 
FOIA requirements, APHIS discloses that request. Thus, by virtue of the 
APHIS process, the fact that the developer is developing the plant and 
its food product would usually already be disclosed.
    FDA also believes that, in most cases, most of the data or 
information provided to FDA during a presubmission consultation would 
not constitute a trade secret or confidential commercial information. 
For example, only a handful of the submissions that FDA has received 
under its current consultation program identified specific data or 
information that the developer claimed to be exempt under Sec. 20.61. 
Neverthelesss, there could be circumstances where a developer initiates 
a presubmission consultation about a product that has not previously 
been disclosed to the public and has grounds to claim that the fact of 
the consultation should not be available for public disclosure. In such 
circumstances, disclosing any data or information in the applicable 
submission would reveal the existence of the submission. Thus, as long 
as the existence of the consultation is exempt from disclosure, all 
data or information in the submission would necessarily be exempt from 
disclosure.

C. Standard Procedures

    FDA is proposing that a prospective notifier ask FDA in writing for 
an opportunity to consult about a bioengineered food (proposed 
Sec. 192.10(e)). A written request would provide clarity about the 
subject of the consultation.
    FDA is proposing to require that a prospective notifier who 
initiates a consultation inform FDA whether, in his view, the fact of 
the consultation with FDA is confidential, and whether, in his view, 
any or all of the provided data or information is confidential 
(proposed Sec. 192.10(f)(1)). FDA also is proposing to require that a 
prospective notifier who claims confidentiality for the existence or 
content of a presubmission consultation explain the basis for that 
claim (proposed Sec. 192.10(f)(2)). FDA is proposing these requirements 
because of the significant public interest in bioengineered foods. 
These requirements would ensure that FDA is aware of the prospective 
notifier's position regarding the availability for public disclosure of 
the existence and content of the

[[Page 4715]]

consultation. In addition, FDA believes that these requirements would 
alert a prospective notifier to the fact that the data or information 
contained in a submission to FDA are available for disclosure unless 
the applicable criteria for exemption are satisfied.
    FDA is proposing to recommend that a prospective notifier send FDA 
a synopsis about the requested consultation (proposed 
Sec. 192.10(f)(3)). The recommended synopsis would include the 
prospective notifier's name and address, the name of the bioengineered 
food and the plant species from which it is derived, a distinctive 
designation(s) that the notifier uses to identify the applicable 
transformation events, a list of the identity(ies) and source(s) of 
introduced genetic material, a description of the purpose or intended 
technical effect of the transformation event (including expected 
significant changes in the composition or characteristic properties of 
food derived from the plant as a result of the transformation event, 
regardless of whether these changes result from the insertion of new 
genes or from a modification in the expression of endogenous genes), a 
description of the applications or uses of the bioengineered food, and 
a description of any applications or uses of the bioengineered food 
that are not suitable for the bioengineered food. FDA is proposing to 
recommend this synopsis because the agency believes that the 
information in the synopsis is both necessary and sufficient to 
characterize the bioengineered food in a manner that will enable the 
agency to engage in a meaningful dialogue with the prospective 
notifier. For example, information about the identity and intended 
technical effect of the transformation event would enable the agency to 
address the potential issue that the food would contain an unapproved 
food additive. A distinctive designation that the notifier uses to 
identify the applicable transformation event would enable the agency to 
efficiently locate other agency records regarding that transformation 
event. It would also facilitate discussions with APHIS and EPA, if 
sponsors use those same designations in information supplied to the 
other agencies. Information about the sources of the genetic material 
would enable the agency to identify issues associated with a known 
allergenic source. Information about expected significant changes in 
the composition of the food would enable the agency to discuss 
suggestions for an appropriate common or usual name for the 
bioengineered food. Information about the applications or uses of the 
food would enable the agency to identify applicable regulatory 
situations (e.g., whether the bioengineered food would likely be used 
in human food, animal feed, or both). Information about any 
applications or uses that the notifier believes would not be suitable 
for the bioengineered food would enable the agency to identify 
potential safety questions, if any, about such use of the bioengineered 
food.
    FDA is proposing that a prospective notifier send a request for 
consultation regarding a bioengineered food to CFSAN (proposed 
Sec. 192.10(g)). As necessary and appropriate, CFSAN would coordinate 
the consultation process with CVM. The proposed regulation is 
consistent with the approach in the 1996 procedures, which has worked 
well.
    FDA is proposing that a prospective notifier should send an 
original and two paper copies of a written request for consultation and 
of any additional materials that are sent to FDA during the 
consultation process (proposed Sec. 192.10(h)(1) and (h)(2)). FDA is 
proposing an original and two copies of these submissions for 
efficiency in providing information about the presubmission 
consultation to the agency's scientific reviewers.
    Because it is likely the data or information in a presubmission 
consultation would be requested under FOIA by an outside party, FDA is 
proposing that a prospective notifier who claims that certain data or 
information provided to FDA during the presubmission consultation are 
exempt from disclosure should clearly identify, in each submission, the 
data or information at issue (proposed Sec. 192.10(h)(3)(i)). When this 
is the case, FDA also is proposing that the prospective notifier should 
provide an additional paper copy of the submission that does not 
contain such data or information (i.e., a redacted paper copy under 
proposed Sec. 192.10(h)(3)(ii)). Providing a redacted copy would 
communicate very clearly which data or information the prospective 
notifier considers to be exempt. These recommendations are consistent 
with a practice that is commonly used by firms who send FDA a food 
additive petition that contains information that the petitioner claims 
to be confidential, a practice that has worked well. In addition, the 
practice of providing a redacted copy also has been used in a few cases 
under the 1996 procedures.
    FDA is proposing that the redacted paper copy be prepared in a 
manner that clearly identifies the location and relative size of 
deleted information. This proposed regulation is consistent with FDA's 
proposed regulations (64 FR 60143, November 4, 1999) regarding 
implementation of the Electronic Freedom of Information Act Amendments 
of 1996 (EFOIA (Public Law 104-231)). EFOIA includes, among other 
things, provisions requiring agencies to inform requesters about the 
amount of information not being released to them.
    FDA is proposing to specify the materials that the agency would 
place in an administrative file that it establishes for a presubmission 
consultation (proposed Sec. 192.10(i)(1)). These materials include any 
correspondence between the prospective notifier and FDA, any written 
materials that the prospective notifier provides during the 
consultation process, and a memorandum of each meeting or significant 
phone call between FDA and the prospective notifier during the 
consultation. This part of the regulation would inform both prospective 
notifiers and outside parties of the materials that ordinarily would be 
in the administrative file of the consultation and thus potentially be 
subject to disclosure under FOIA.
    FDA's proposal includes its commitment to discuss issues associated 
with a bioengineered food with any prospective notifier who asks to do 
so (proposed Sec. 192.10(i)(2)). FDA is proposing to include this 
commitment to both remind and encourage prospective notifiers that the 
purpose of the recommended program is for a prospective notifier to 
engage FDA in a discussion about the bioengineered food at an early 
stage of the food's development. However, the agency realizes that 
there may be circumstances where such a discussion would not be an 
efficient use of resources for either the prospective notifier or for 
FDA. For example, a prospective notifier may intend to notify FDA about 
bioengineered foods that derive from a series of plant lines that are 
the result of independent transformation events with the same genetic 
construct. After FDA has completed its evaluation of one of these 
bioengineered foods, the notifier likely would be aware of most or all 
of the applicable safety, nutritional, or other regulatory issues that 
could be associated with the food. Nevertheless, FDA would welcome the 
opportunity to be informed about the notifier's plans to submit 
additional notices because this information could help the agency to 
plan its workload.
    The proposed regulation describes a flexible process for any 
discussion (e.g., by mentioning that the discussion could

[[Page 4716]]

take place through a meeting or through a telephone conference). FDA is 
highlighting the opportunity to discuss the bioengineered food by a 
mechanism other than a face-to-face meeting to minimize the potential 
that a small business or academic research group would elect not to 
participate in the program due to the cost of travel. Given the 
agency's experience under the current consultation process, FDA is 
confident that a meaningful dialogue can often be accomplished without 
a face-to-face meeting.

VII. Premarket Biotechnology Notice: Administrative Information

    FDA is proposing to codify certain administrative information that 
would apply to a PBN (proposed Sec. 192.20). The proposed 
administrative information includes information about where to send a 
PBN, the number of copies to send, how to include information in a 
foreign language, how to refer to data or information that are already 
in FDA's files, how to obtain guidance on scientific issues, and the 
prerogative of a notifier to withdraw a PBN from FDA's consideration. 
Many of these administrative aspects of the proposed notification 
program are consistent with procedures already in place for the food 
additive petition program (Sec. 171.1 (21 CFR 171.1)). FDA discusses 
the details of these administrative aspects of the proposed 
notification program immediately below.

A. Submissions to CFSAN for Use in Human Food, Animal Feed, or Both

    FDA is proposing that a notifier send a PBN regarding a 
bioengineered food to CFSAN (proposed Sec. 192.20(a)). As necessary and 
appropriate, CFSAN would coordinate FDA's evaluation of the PBN with 
CVM. The proposed regulation is consistent with the approach that FDA 
recommended in the 1996 procedures, an approach that has worked well.

B. Paper Copies

    FDA is proposing that a prospective notifier send to the agency an 
original paper version and one paper copy of a PBN (including any 
amendments) (proposed Sec. 192.20(b)(1)). A notifier would have an 
option to submit one additional paper copy or, under proposed 
192.20(c)(1), to submit an electronic copy that is formatted in a 
manner that makes it suitable for FDA to use while evaluating the PBN. 
The number of paper copies required by the regulation is consistent 
with the number of paper copies that FDA currently requires for other 
premarket submissions, such as a food additive petition. A requirement 
for multiple paper copies generally serves the purpose of providing a 
copy of the submission to multiple scientific reviewers. However, as 
discussed below, FDA also is recommending that a notifier submit an 
electronic copy of a PBN that is formatted in a manner that makes it 
suitable for FDA to use in evaluating a PBN. Because scientific 
reviewers could accomplish their review by accessing the electronic 
copy, under the proposed rule, a notifier who submits an electronic 
evaluation copy would submit one less paper copy. FDA would retain the 
original paper version at CFSAN, while the paper copy would be retained 
at CVM. Comments may result in a modification to the proposed 
requirement to submit a single paper copy.
    Under the regulation, the paper copy would be the official version 
at FDA. This provision would clarify the status of an electronic copy 
that FDA also is proposing to require \11\ (see proposed 
Sec. 192.20(c)(1) and section VII.C of this document).
---------------------------------------------------------------------------

    \11\ Under 21 CFR 11.1(c), an electronic record that meets the 
requirements of 21 CFR part 11 may be used in lieu of a paper 
record, unless paper records are specifically required. However, 
CFSAN is not prepared, at this time, to accept an electronic record 
as the official record because CFSAN does not yet have specific 
guidance for the submission of records only in electronic form.
---------------------------------------------------------------------------

    FDA is proposing that a notifier who claims that specific data or 
information in the PBN are confidential must prepare and submit one 
paper copy of the PBN that does not contain any of those data or 
information (proposed Sec. 192.20(b)(2)). Consistent with the EFOIA 
proposed rule, the notifier would prepare this redacted paper copy in a 
manner that clearly identifies the location and relative size of 
deleted information. As discussed previously regarding a presubmission 
consultation (see section VI.C of this document), the redacted copy 
would be very useful as it would communicate very clearly which data or 
information the notifier considers to be exempt from disclosure.

C. Electronic Copies

    FDA is proposing to include in the regulation a recommendation that 
a notifier submit an electronic copy (the evaluation copy) that is 
formatted in a manner that makes it suitable for FDA to use while 
evaluating the PBN (proposed Sec. 192.20(c)(1)). Because technology is 
advancing at a rapid pace, the regulation would inform notifiers how to 
obtain information about the appropriate format of the electronic copy 
rather than specify that format. Under the regulation, a notifier would 
provide such an electronic copy of both the original PBN and of any 
amendments to the PBN. FDA is recommending the submission of an 
electronic evaluation copy to take advantage of the fact that 
contemporary technology makes it possible for notifiers to send, and 
FDA to evaluate, submissions of data or information in electronic form, 
and the availability of an electronic evaluation copy has the potential 
to improve the efficiency of FDA's review. To encourage manufacturers 
to submit an electronic evaluation copy, a notifier who submits such a 
copy would submit a total of two, rather than three, paper copies.
    FDA also is proposing to require that a notifier submit an 
electronic copy (the disclosure copy) that is formatted in a manner 
that makes it suitable for FDA to use to make a PBN available to the 
public in an electronic reading room (proposed Sec. 192.20(c)(2)). As 
would be the case with the electronic evaluation copy, the regulation 
would inform notifiers how to obtain information about the appropriate 
format of the electronic copy and a notifier would be required to 
provide such an electronic copy of both the original PBN and of any 
amendments to the PBN. Consistent with the EFOIA proposed rule, a 
notifier would delete data or other information claimed to be 
confidential from the electronic copy in a manner that clearly 
identifies the location and relative size of deleted information. FDA 
is proposing to require an electronic disclosure copy to facilitate the 
agency's compliance with EFOIA, which includes provisions regarding the 
availability of records in electronic form and the establishment of 
``electronic reading rooms.'' As discussed in the EFOIA proposed rule, 
section 4 of EFOIA (5 U.S.C. 552(a)(2)(D)) adds a new category of 
records that agencies must make available in their public reading 
rooms. This new category consists of copies of records that have been 
released to any person under FOIA and that, because of their subject 
matter, the agency determines have become or are likely to become the 
subject of subsequent requests for substantially the same records. In 
light of the significant public interest in bioengineered foods and in 
FDA's oversight of these foods, FDA has tentatively concluded that it 
is likely that each submitted PBN would be requested under FOIA 
multiple times.
    The preparation of an electronic copy formatted in a manner that 
makes it suitable for FDA to use to make a PBN available to the public 
in an electronic reading room will require use of computer technology. 
Although the use

[[Page 4717]]

of this technology is widespread, it is possible that a firm that 
develops a bioengineered food would not have access to the particular 
technology that will be needed. For this reason, under the proposed 
regulation a notifier may request a waiver from the requirement to 
submit an electronic disclosure copy. FDA would grant or deny the 
notifier's request on its merits.
    FDA requests comments on its proposal to require an electronic 
disclosure copy of a PBN and to provide a notifier with an opportunity 
to request a waiver from this requirement. Such comments may result in 
a modification to the proposed requirement to submit such a copy.

D. English Language Translations, Incorporation by Reference, and 
Available Guidance Documents

    FDA is proposing that a notifier who submits any material in a 
foreign language provide an English translation that is verified to be 
complete and accurate (proposed Sec. 192.20(d)). This proposed 
regulation is necessary for the agency's efficient evaluation of a PBN 
and is consistent with other agency regulations regarding the 
submission of information in a foreign language (see e.g., 
Sec. 171.1(a) and the agency's recent proposal for a premarket 
notification program for food contact substances (65 FR 43269, July 3, 
2000)).
    FDA is proposing that a notifier may incorporate by reference data 
or information that are already retained in FDA's files (proposed 
Sec. 192.20(e)). The proposed regulation specifies that a notifier may 
simply incorporate by reference a file that the notifier previously 
submitted. If the notifier wishes to incorporate by reference a file 
that someone else previously submitted to FDA, the procedure to 
incorporate that file into the PBN depends on whether the file is 
publicly available (e.g., the file is in an electronic reading room or 
is otherwise available under FOIA). If the file is publicly available, 
a notifier may incorporate that file by referring FDA to it. If the 
file is not publicly available, a notifier may incorporate that file by 
referring FDA to it if the person who submitted the file authorizes the 
notifier to do so in a signed statement and the notifier includes that 
signed statement in the PBN. This proposed provision is similar to that 
described for incorporating previously submitted information into a 
food additive petition (Sec. 171.1(b)) and to that described in the 
agency's recent proposal for a premarket notification program for food-
contact substances (65 FR 43269, July 13, 2000).
    FDA is proposing to inform notifiers that they can obtain current 
guidance regarding specific technical issues by writing to FDA or by 
looking on FDA's site on the Internet (proposed Sec. 192.20(f)). FDA is 
adding this provision to assist notifiers in addressing common 
technical issues, such as the estimation of dietary exposure to 
substances that are present in food. FDA expects that this provision 
will minimize the time spent, by the agency and the notifier, on 
routine technical issues.

E. Opportunity to Withdraw

    FDA is proposing to codify a provision that a notifier may request, 
at any time during FDA's evaluation of a PBN, that FDA cease to 
evaluate that PBN (proposed Sec. 192.30(g)). Under the regulation, the 
notifier could submit a future PBN about the same bioengineered food. 
FDA would retain the PBN in its files and would classify it as 
``withdrawn.'' A notifier could choose to withdraw a notice for several 
reasons. For example, it is possible that discussions between the 
notifier and FDA would result in a decision by the notifier to 
substantially revise the notice to provide data or information that 
address the applicable legal status questions in a more thorough manner 
than the submitted PBN.
    The proposed regulation is consistent with the provisions of the 
food additive premarket review program (Sec. 171.7). Although a 
notifier does not need explicit authorization to withdraw a notice, a 
notifier may not be aware of this fact. Likewise, a notifier may not be 
aware that a notice that is ``withdrawn'' remains an agency record that 
could be requested under FOIA. Thus, the regulation would both clarify 
a prerogative accorded to a notifier and inform the notifier of 
consequences associated with that prerogative.

VIII. Premarket Biotechnology Notice: Required Parts

    FDA is proposing that a PBN be separated into seven parts (proposed 
Sec. 192.25). These would include a letter (proposed Sec. 192.25(a)); a 
synopsis (proposed Sec. 192.25(b)); administrative statements about the 
status of review of the bioengineered food by other Federal agencies or 
by foreign governments (proposed Sec. 192.25(c)); data or information 
about the method of development (proposed Sec. 192.25(d)); a discussion 
of any newly inserted genes that encode resistance to an antibiotic 
(proposed Sec. 192.25(e)); data or information about substances 
introduced into, or modified in, the food (proposed Sec. 192.25(f)); 
and data or information about the food (proposed Sec. 192.25(g)). The 
proposed regulation fosters a case-by-case approach to addressing 
relevant scientific and regulatory issues rather than a single set of 
tests that likely would not be applicable in all circumstances. In 
general, the proposed requirements derive from the 1992 policy, the 
1996 procedures, and FDA's experience under the 1996 procedures. In 
proposing these requirements, FDA also has drawn on its experience in 
administering a proposed notification program for GRAS substances (62 
FR 18938, April 17, 1997).\12\
---------------------------------------------------------------------------

    \12\ FDA has not yet issued a final rule based on the GRAS 
proposal. However, in the GRAS proposal, FDA invited interested 
persons who determine that a use of a substance is GRAS to notify 
FDA of such GRAS determinations during the interim between the 
proposed and final rules (the interim period). During this interim 
period, FDA has received several dozen GRAS notices, which provided 
practical experience both with theoretical issues raised by that 
rulemaking and with practical issues associated with establishing an 
efficient program.
---------------------------------------------------------------------------

    The proposed regulation reflects FDA's current judgment based on 
contemporary scientific methods for development of bioengineered foods 
and the types of bioengineered foods that are now under development. 
Accordingly, the proposed regulation focuses on modifications to foods 
that are likely to result in commercial products and does not attempt 
to predict future changes in foods that may result from technological 
advances. In this field of rapid scientific development, if 
circumstances warrant, FDA would propose to revise any regulation that 
results from this proposal. FDA requests comment on technological 
advances in rDNA technology that are likely to result in commercial 
products and that would not be addressed by the proposed submission 
requirements. Such comments may result in a modification to the 
proposed submission requirements.

A. Part I: Letter

    FDA is proposing to require that a responsible official of the 
notifier's organization, or the notifier's attorney or agent, date and 
sign a letter that informs FDA that the notifier is submitting a PBN 
under proposed Sec. 192.25. In the letter, this official, attorney, or 
agent would state his position or title and attest to five statements.
1. Statements Regarding the Notifier's Responsibility and the Balanced 
Nature of the Notice
    FDA is proposing to require that a notifier inform FDA that it is 
the

[[Page 4718]]

notifier's view that the bioengineered food is as safe as comparable 
food and that the intended use of the bioengineered food is in 
compliance with all applicable requirements of the act (proposed 
Sec. 192.25(a)(1)). Applicable requirements of the act would include, 
for example, the requirement under section 409(a) and 402(a)(2)(C) of 
the act for FDA review and approval of a food additive and the 
requirement under section 201(n) and 403 of the act that labeling for 
the food be appropriate. FDA also is proposing that a notifier state 
that to the best of the notifier's knowledge, the PBN is a 
representative and balanced submission that includes information, 
unfavorable as well as favorable, pertinent to the evaluation of the 
safety, nutritional, or other regulatory issues that may be associated 
with the bioengineered food (proposed Sec. 192.25(a)(2)). FDA is 
proposing that the notifier attest to these statements because, under 
the act, developers of new foods have a responsibility to ensure that 
the foods they offer to consumers are safe and in compliance with all 
requirements of the act (57 FR 22984 at 22985).
    FDA is proposing the standard ``as safe as'' because this is the 
standard that the agency currently uses to evaluate a notice that is 
submitted under the 1996 procedures. Because the proposed standard is a 
comparative standard (``as safe as''), it takes into account 
circumstances such as the existence of naturally occurring toxicants in 
many plants (e.g., solanine that occurs naturally in potatoes). As 
discussed below (see section VIII.G.1 and proposed Sec. 192.25(g)(1)), 
FDA also is proposing that the notifier provide a justification for 
selecting a particular food or foods as the ``comparable food'' to 
which the notifier will compare the bioengineered food.
2. Statements Regarding the Availability of Data and Information for 
FDA's Review
    FDA is proposing to require that a notifier agree to make relevant 
data or information that are not included in the PBN available to FDA 
upon request while FDA is evaluating the PBN or for cause (proposed 
Sec. 192.25(a)(3)). FDA is proposing this requirement to ensure that 
the agency will have access to relevant data or other information if 
safety questions arise after the bioengineered food enters commercial 
distribution. This proposed requirement will also continue a practice 
that began under the 1996 procedures.
    FDA also is proposing that a notifier agree to two procedures for 
making such data or information available to FDA (proposed 
Sec. 192.25(a)(4)). The first procedure is to allow FDA to review and 
copy these data or information at a specified address during customary 
business hours. The second procedure is to send these data or 
information to FDA. FDA is proposing that a notifier agree to both of 
these two procedures to provide flexibility and efficiency to both the 
notifier and the agency.
3. Statement Regarding Public Disclosure
    FDA is proposing that a notifier inform FDA as to whether the 
notifier claims that the existence of a PBN, or any or all of the data 
or information in the PBN, is exempt from disclosure under the FOIA and 
explain the basis for that claim (proposed Sec. 192.25(a)(5)). FDA is 
proposing these requirements in light of the significant public 
interest in bioengineered foods. These requirements would ensure that 
FDA is aware of the notifier's position regarding the availability for 
public disclosure of the existence and content of a PBN. In addition, 
FDA believes that these requirements would alert a notifier that the 
data or information contained in a PBN are available for disclosure 
unless the applicable criteria for exemption are satisfied.
    As discussed more fully below, this proposed rule assumes that the 
existence and content of a PBN is available for public disclosure 
unless the notifier establishes that the existence of the notice 
constitutes confidential commercial information or that specific data 
or information in the PBN constitute a trade secret or confidential 
commercial information. Thus, the proposed rule acknowledges that there 
could be circumstances in which the existence or content (or a portion 
of the content) of a PBN would be eligible for an exemption from public 
disclosure.

B. Part II: Synopsis

    FDA is proposing that the first section of a PBN be a synopsis 
(proposed Sec. 192.25(b)) that includes the same information that FDA 
is recommending for inclusion in a presubmission consultation (see 
proposed Sec. 192.10(f)(3) and section VI.C of this document). The 
synopsis would be a concise document that describes the bioengineered 
food in a manner that is suitable for preparing a publicly accessible 
list of PBN's (see proposed Sec. 192.40(c)(1)(i) and section X.A of 
this document).

C. Part III: Status at Other Federal Agencies and Foreign Governments

    FDA is proposing that a notifier inform FDA of the status of any 
prior or ongoing evaluation of the bioengineered plant, or food derived 
from such a plant, by USDA/APHIS and EPA (proposed Sec. 192.25(c)(1) 
and (c)(2)). The proposed regulation is consistent with the 
recommendations in a report issued in April 2000 by the National 
Research Council (the 2000 NRC Report) (Ref. 14). That report 
recommended, among other things, that FDA, EPA, and USDA/APHIS 
establish a process to ensure appropriate and timely exchange of 
information between agencies about bioengineered pest-protected plants. 
Under the regulation, FDA would be aware of any issues still pending at 
those agencies, that are relevant to FDA's evaluation of the 
bioengineered food in question. When necessary and appropriate, FDA 
would contact APHIS, EPA, or both agencies about their evaluation of 
the bioengineered plant.
    In addition, as discussed previously in this notice, the purpose of 
this notification program is to provide FDA with the information 
necessary to determine whether there are legal status questions 
concerning a bioengineered food so as to permit FDA to carry out its 
enforcement responsibilities. This would include its responsibilities 
to enforce section 402(a)(2)(B) of the act, which addresses foods 
containing illegal pesticide residues.\13\ If the EPA regulatory 
process regarding the bioengineered food is not yet complete and a 
tolerance or exemption from tolerance has not been established, the 
food would not be in full compliance with the law. Accordingly, in 
these circumstances, FDA would inform a notifier that the agency does 
not consider the notifier's PBN to satisfy the requirement for 
premarket notice (see proposed Sec. 192.30(e) and section IX.C.5 of 
this document).
---------------------------------------------------------------------------

    \13\ Under the Federal Insecticide, Fungicide, and Rodenticide 
Act (FIFRA), EPA registers pesticides, including those introduced 
into food via bioengineering; under section 408 of the act (21 
U.S.C. 346a), EPA sets a tolerance or grants an exemption from a 
tolerance for pesticide residues in food. FDA has the statutory 
responsibility to enforce these tolerances or exemptions; under 
section 402(a)(2)(B), a food is adulterated if it contains a 
pesticide residue that exceeds an established tolerance or for which 
there is no tolerance or exemption from the requirement for a 
tolerance.
---------------------------------------------------------------------------

    FDA also is proposing that a notifier inform FDA as to whether the 
bioengineered food is or has been the subject of review by any foreign 
government and, if so, describe the status of that review (proposed 
Sec. 192.25(c)(3)). Foreign countries have instituted various 
regulatory requirements for bioengineered foods. Information about the 
status of a notifier's submission(s) to foreign

[[Page 4719]]

countries could be pertinent to FDA's review. For example, some issues 
raised by a foreign country could be relevant to the legal status of 
the bioengineered food under the act.

D. Part IV: Method of Development

    FDA is proposing that a PBN include data or information about the 
method of development (proposed Sec. 192.25(d)). Specifically, FDA is 
proposing that the data or information that a notifier provides 
regarding the method of development include: (1) Characterization of 
the parent plant including scientific name, taxonomic classification, 
mode of reproduction, and pertinent history of development (proposed 
Sec. 192.25(d)(1)); (2) construction of the vector used in the 
transformation of the parent plant, with a thorough characterization of 
the genetic material intended for introduction into the parent plant 
and a discussion of the transformation method, open reading frames, and 
regulatory sequences (proposed Sec. 192.25(d)(2)); (3) characterization 
of the introduced genetic material, including the number of insertion 
sites, the number of gene copies inserted at each site, and information 
on DNA organization within the inserts; and information on potential 
reading frames that could express unintended proteins in the 
transformed plant (proposed Sec. 192.25(d)(3)); and (4) data or 
information related to the inheritance and genetic stability of the 
introduced genetic material (proposed Sec. 192.25(d)(4)). The proposed 
requirement derives from the 1992 policy, the 1996 procedures, and 
FDA's experience under the 1996 procedures. FDA requests comment on 
technological advances in rDNA technology that are likely to result in 
commercial products and that would not be addressed by the proposed 
submission requirements. Such comments may result in a modification to 
the proposed submission requirements.
    FDA also is proposing to require that a notifier include a 
discussion, as necessary, of other relevant data or information about 
the method of development (proposed Sec. 192.25(d)(5)). This 
requirement would cover any issues about the method of development that 
are not explicitly addressed in proposed Sec. 192.25(d)(1), (d)(2), 
(d)(3), and (d)(4). FDA expects that such issues would be identified 
during presubmission consultations on specific products.

E. Part V: Antibiotic Resistance

    In September 1998, FDA issued for public comment a draft guidance 
document regarding the use of antibiotic resistance markers in 
bioengineered plants (the 1998 draft antibiotic resistance guidance 
(Ref. 15)).\14\,\15\ Consistent with the thinking presented in that 
document, FDA is proposing to require that a PBN include a discussion 
about any newly inserted genes that encode resistance to an antibiotic 
(proposed Sec. 192.25(e)). Because scientific methods to assess this 
issue are evolving, in the proposed regulation FDA is recommending that 
a notifier contact FDA about the agency's current thinking on this 
topic.
---------------------------------------------------------------------------

    \14\ In the 1992 policy, FDA discussed the role of genes that 
encode resistance to an antibiotic as part of the development of 
some bioengineered foods (57 FR 22984 at 22987). In the APH(3')II 
final rule, FDA approved the use of the enzyme expressed by one such 
gene, the kan<SUP>r</SUP> gene encoding resistance to kanamycin, in 
the development of new varieties of cotton, oilseed rape, and 
tomatoes. Between November 1996, and February 1997, FDA had several 
discussions with outside experts to determine whether circumstances 
exist under which FDA should recommend that a given antibiotic 
resistance gene not be used in crops intended for food use, and if 
so, to delineate the nature of those circumstances. Based on these 
discussions, FDA issued for public comment the 1998 draft antibiotic 
resistance guidance. FDA intends to issue final guidance in the near 
future.
    \15\ A report that describes the consultations that FDA relied 
on in developing this draft guidance is available (Ref. 16).
---------------------------------------------------------------------------

F. Part VI: Substances in the Food

    FDA is proposing that a PBN include data or information about 
substances introduced into, or modified in, the food (proposed 
Sec. 192.25(f)). These data or information would include data or 
information about the identity and function of these substances 
(proposed Sec. 192.25(f)(1)), the level of these substances in the 
bioengineered food (proposed Sec. 192.25(f)(2)), dietary exposure to 
these substances (proposed Sec. 192.25(f)(3)), the potential that a 
protein introduced into the food will be an allergen (proposed 
Sec. 192.25(f)(4)), and a discussion of other safety issues that may be 
associated with these substances (proposed Sec. 192.25(f)(5)). In 
general, the proposed requirements derive from the 1992 policy, the 
1996 procedures, and FDA's experience under the 1996 procedures. FDA 
requests comment on these proposed submission requirements. Such 
comments may result in a modification to the proposed submission 
requirements.
1. Covered Substances
    FDA is proposing that a notifier provide data or information about 
substances introduced into, or modified in, the food (proposed 
Sec. 192.25(f)). Under the regulation, a ``modified substance'' would 
include a substance that is present in the bioengineered food at an 
increased level relative to comparable food. Because pesticidal 
substances are regulated by EPA, the proposed regulation regarding data 
and information about substances introduced into the plant excludes 
data and information about pesticidal substances.
    As discussed previously (section II of this document), a 
nonpesticidal substance introduced into food by way of breeding is a 
food additive if the substance is not GRAS within the meaning of 21 
U.S.C. 321(s). Thus, the legal status issues raised by bioengineered 
foods include the potential that the food would contain an unapproved 
food additive. In the 1992 policy, FDA expressed its view that there is 
unlikely to be a safety question sufficient to question the presumed 
GRAS status of the expression products of the transferred genetic 
material when the expression products do not differ significantly from 
other substances commonly found in food and are already present at 
generally comparable or greater levels in currently consumed foods (57 
FR 22984 at 22990). In the 1992 policy, FDA identified proteins, 
carbohydrates, and fats and oils as substances commonly found in food 
because those were the substances that were being considered in 
products under development in 1992.\16\ As discussed, rDNA technology 
has recently begun to be used to introduce multiple genes to generate 
new metabolic pathways (Ref. 11). As with proteins, carbohydrates, and 
fats and oils, it is FDA's view that the substances produced by the new 
pathways would be presumed to be GRAS if they do not differ 
significantly from other substances that are currently present at 
generally comparable or greater levels in food and, as such, are safely 
consumed.
---------------------------------------------------------------------------

    \16\ As discussed in the 1992 policy, FDA has presumed that 
transferred nucleic acids would be GRAS (57 FR 22990). Under the 
proposed regulation, a notifier provides data or other information 
about transferred nucleic acids in Parts IV (method of development) 
and V (genes that encode resistance to an antibiotic).
---------------------------------------------------------------------------

2. Identity, Function, Level, and Dietary Exposure
    FDA is proposing that a PBN include data or information about the 
identity and function of substances introduced into, or modified in, 
the food (proposed Sec. 192.25(f)(1)) and the level in the 
bioengineered food of these substances (proposed Sec. 192.25(f)(2)). 
The proposed regulation derives from the fact that the quantity and 
quality of scientific evidence required to establish that the use of a 
substance is safe vary

[[Page 4720]]

considerably depending upon the chemical, physical, and physiological 
properties of the substance and its estimated dietary exposure.
    FDA is proposing that a notifier include either: (1) An estimate of 
dietary exposure to substances introduced into, or modified in, the 
food (proposed Sec. 192.25(f)(3)(i)); or (2) a statement that explains 
the basis for the notifier's conclusion that an estimate of dietary 
exposure to these substances is not needed to support safety (proposed 
Sec. 192.25(f)(3)(ii)). As discussed in the 1992 policy (57 FR 22984 at 
22998), many substances that would be introduced into, or modified in, 
a bioengineered food would be present in the bioengineered food at a 
relatively low level. For example, since 1994, developers have 
completed more than 45 consultations about bioengineered foods, most of 
which contain newly introduced or modified enzymes (Ref. 6). In most 
cases, an estimate of dietary exposure to these enzymes was not 
critical to the safety assessment. However, this is not always the 
case, even for enzymes that would be present in food at a low level. 
For example, in the case of the enzyme APH(3')II, FDA relied, in part, 
on the estimated dietary exposure to APH(')II in concluding that active 
APH(3')II in food would not interfere with the clinical efficacy of the 
orally administered antibiotic, kanamycin (59 FR 26700 at 26703). Thus, 
the particular circumstances will determine whether an actual estimate 
of dietary exposure to a substance that is introduced into a food plant 
is needed to support the notifier's view that the bioengineered food is 
as safe as comparable food.
3. Allergenicity
    FDA is proposing that a notifier include a discussion of the 
available data or information that address the potential that a protein 
introduced into the food will be an allergen (proposed 
Sec. 192.25(f)(4)). The proposed regulation is consistent with the 1996 
procedures, which recommend that a notifier provide FDA with 
information regarding any known or suspected allergenicity and a 
discussion of the available information about the potential for the 
bioengineered food to induce an allergic response. Because scientific 
methods to assess this issue are evolving, in the proposed regulation 
FDA is recommending that a notifier contact FDA about the agency's 
current thinking on this topic.
    FDA is developing guidance for evaluating the potential 
allergenicity of proteins introduced into bioengineered foods and 
intends to make that draft guidance available for public comment in the 
near future. The draft guidance will be based in part on 
recommendations made by scientific experts who attended a public 
scientific conference on food allergy and bioengineered foods that FDA, 
EPA, and USDA jointly hosted on April 18 and 19, 1994 (the 1994 
allergenicity conference (Ref. 17)).\17\
---------------------------------------------------------------------------

    \17\ The goal of the 1994 allergenicity conference was to foster 
a scientific dialogue to assess information that was available at 
that time regarding the characteristic properties of food allergens 
and the methods that are available to assess allergenicity. The 
scientists who participated in this conference noted that serum from 
an individual who is sensitive to a known allergenic source can be 
used to assess the allergenic potential of proteins derived from 
that source. These scientists acknowledged that there are no direct 
methods to assess allergenicity of proteins from sources that are 
not known to produce food allergy. However, they suggested that the 
possibility that a new protein will cause an allergic reaction can, 
to some degree, be evaluated by comparing its similarity to 
characteristics of known food allergens. If a protein does not have 
characteristics of known food allergens, the potential that the 
protein would cause an allergic reaction is minimized. Because 
exceptions have been reported for the observed characteristics of 
allergens, and no one factor is fully predictive, the scientists 
recommended that an assessment of allergenicity be based on all 
available information. 
---------------------------------------------------------------------------

4. Other Safety Issues
    It is impracticable for FDA to either anticipate all classes of 
substances that could be introduced into food or provide specific 
guidance about each of those classes of substances. Therefore, FDA is 
proposing that a notifier provide a discussion of data or information 
relevant to other safety issues that may be associated with the 
substances introduced into, or modified in, the food (proposed 
Sec. 192.25(f)(5)). This requirement would cover any issues that are 
not explicitly addressed in proposed Sec. 192.25(f)(1), (f)(2), (f)(3), 
and (f)(4) regarding substances introduced into, or modified in, the 
food. Such issues could include, for example, the digestibility or 
toxicity of an introduced protein. FDA expects that such issues would 
be identified during presubmission consultations on specific foods.

G. Part VII: Data and Information About the Food

    FDA is proposing that a notifier provide data or information about 
the bioengineered food (proposed Sec. 192.25(g)). These data or 
information would include a justification for selecting a particular 
food(s) as ``comparable food'' (proposed Sec. 192.25(g)(1)); a 
discussion of historic uses of the comparable food(s) (proposed 
Sec. 192.25(g)(2)); data or information comparing the composition and 
characteristics of the bioengineered food to those of comparable 
food(s), with emphasis on significant nutrients, naturally occurring 
toxicants and antinutrients, and any intended changes to the 
composition of the food (proposed Sec. 192.25(g)(3)); any other 
information relevant to the safety, nutritional, or other regulatory 
assessment of the bioengineered food (proposed Sec. 192.25(g)(4)); and 
a narrative that explains the basis for the notifier's view that the 
bioengineered food is as safe as comparable food(s) and that the 
bioengineered food is otherwise in compliance with all applicable 
requirements of the act (proposed Sec. 192.25(g)(5)). In general, the 
proposed requirements derive from the 1992 policy, the 1996 procedures, 
and FDA's experience under the 1996 procedures. FDA discusses the 
details of this proposed regulation immediately below. FDA requests 
comment on the proposed submission requirements regarding the food. 
Such comments may result in a modification to the proposed submission 
requirements.
1. Comparable Food
    FDA is proposing that the notifier provide a justification for 
selecting a particular food or foods as the ``comparable food'' to 
which the notifier will compare the bioengineered food (proposed 
Sec. 192.25(g)(1)). The proposed requirement is based on the 1992 
policy and FDA's experience under the 1996 procedures.
    Ordinarily, the comparable food would be the parental variety or 
commonly consumed varieties of the parent plant (57 FR 22984 at 22996 
and Ref. 5)). However, when the intended effect of the transformation 
is to change the composition of the food, it may be appropriate to also 
compare the composition and characteristics of the bioengineered food 
to that of another commonly consumed food. For example, if an oilseed 
crop is modified to produce an oil that has a higher content of a 
particular fatty acid than commonly consumed varieties, it may be 
appropriate to also compare the composition and characteristics of the 
bioengineered food to that of a food that contains that fatty acid. FDA 
expects that any issues associated with the appropriate selection of 
comparable food(s) would be identified during presubmission 
consultations on specific products.
2. Historic Uses of the Comparable Food
    FDA is proposing that the notifier provide a discussion of historic 
uses of the comparable food(s) to which the notifier will compare the 
bioengineered food (proposed Sec. 192.25(g)(2)). Several

[[Page 4721]]

notifiers who have consulted with FDA under the 1996 procedures have 
included such a discussion (e.g., as part of their description of the 
applications or uses of the bioengineered food). FDA has found that 
such a discussion is particularly helpful in identifying the potential 
uses of the bioengineered food, regardless of whether those uses are 
specifically targeted by the notifier.
3. Comparing the Composition and Characteristics of the Bioengineered 
Food to That of Comparable Food
    Consistent with the 1992 policy, the 1996 procedures, and FDA's 
experience under the 1996 procedures, FDA is proposing that a notifier 
provide data or information comparing the composition and 
characteristics of the bioengineered food to those of comparable 
food(s), with emphasis on changes in the levels of significant 
nutrients and naturally occurring toxicants and antinutrients (proposed 
Sec. 192.25(g)(3)(i) and (g)(3)(ii)). Such changes could raise legal 
status questions such as whether the name of the food adequately 
describes the food or whether the food is adulterated within the 
meaning of section 402(a)(1) of the act.
    Consistent with the 1992 policy, the 1996 procedures, and FDA's 
experience under the 1996 procedures, FDA is proposing that a notifier 
provide data or information about any intended changes to the 
composition or characteristics of the food (proposed 
Sec. 192.25(g)(3)). Such changes could raise legal status questions 
such as the appropriate common or usual name for the food. For example, 
FDA has been notified about a modification to a canola variety of 
rapeseed to produce an oil with a modified fatty acid composition. 
Because the name that is most often used to describe oil derived from 
the parent plant (i.e., canola oil) did not accurately reflect the 
characteristic properties of the bioengineered oil, the notifier 
suggested a new name for the oil.
    Intended changes to the composition or characteristics of the food 
also could raise safety questions about the food. For example, it is 
possible that a developer could modify corn so that the corn becomes a 
significant dietary source of the nutrient folic acid. Folic acid is 
used to fortify many foods, including breakfast cereals, because of the 
relationship between consumption of folic acid and a reduced risk of 
neural tube defects (21 CFR 101.79). However, excess folic acid in the 
diet can mask the signs of vitamin B<INF>12</INF> deficiency. Thus, an 
increased level of folic acid in a food such as corn, which is commonly 
used in breakfast cereals, could raise safety or other regulatory 
issues.
    Under proposed Sec. 192.25(g)(3), intended changes to the 
composition of food include modifications that are intended to reduce 
the level of a substance in food. For example, it is possible that a 
modification would be intended to decrease the level of a substance 
that is considered undesirable, such as the phytate that naturally 
occurs in soybeans. It also is possible that a modification would be 
intended to reduce the fat content of a food. As with intended 
increases in the level of substances already in food, changes that 
decrease the level of substances already in food could raise legal 
status questions such as the appropriate common or usual name for the 
food.
4. Other Relevant Information
    Consistent with the 1992 policy, the 1996 procedures, and FDA's 
experience under the 1996 procedures, FDA is proposing that a notifier 
provide a discussion of any other information relevant to the safety, 
nutritional, or other regulatory assessment of the bioengineered food 
(proposed Sec. 192.25(g)(4)). This requirement would cover any legal 
status issues about the food that are not explicitly addressed in 
proposed Sec. 192.25(g)(1), (g)(2), and (g)(3). For example, under 
proposed Sec. 192.25(g)(4), a notifier could discuss the basis for 
proposing a specific common or usual name for a bioengineered food, or 
any other proposed labeling that would accompany the bioengineered 
food. FDA expects that such issues would be identified during 
presubmission consultations on specific foods.
    FDA requests comment on whether this rule should also include a 
requirement that a premarket notice for a bioengineered food include 
methods by which the food could be detected. In particular, the agency 
is interested in comments on the circumstances under which such methods 
should or should not be required, and the rationale for any such 
requirement (e.g., the modification to the crop makes the food 
acceptable for animal feed but unacceptable for human food). The agency 
is also interested in comments on whether any such required methods 
should be for raw agricultural commodities, representative finished 
foods likely to contain the modified food, or both; and whether any 
such required methods should contain sufficient information, such as 
primer sequences, to enable technically-proficient non-government 
laboratories to use them; and what other criteria, if any, there should 
be for required methods (e.g., cost). Such comments may result in a 
modification to the proposed submission requirements.
5. Narrative
    FDA is proposing to require that a notifier provide a narrative 
that explains the basis for the notifier's view that the bioengineered 
food is as safe as comparable food and that the bioengineered food is 
otherwise in compliance with all applicable requirements of the act 
(proposed Sec. 192.25(g)(5)). The narrative would provide an integrated 
discussion of the data and information submitted in a PBN. FDA is 
proposing this requirement because the notifier has the responsibility 
for determining that the intended use of the bioengineered food is as 
safe as comparable food and is otherwise lawful. Absent an integrated 
discussion of the underlying data and information, the basis for the 
notifier's conclusion about the legal status of the bioengineered food 
may not be apparent.

IX. Agency Administration of a Premarket Biotechnology Notice

A. Filing Decision

    FDA is proposing to do an initial evaluation of the notice within 
15 working days to see whether the notice appears to include all 
elements required under Secs. 192.20 and 192.25 (proposed 
Sec. 192.30(a)). FDA also is proposing to file a PBN that appears to 
include all required elements, and to contact a notifier to explain 
what is missing if the PBN does not appear to include all required 
elements. FDA is proposing this ``filing decision'' because the 
timeframe for the agency's response to the notifier (i.e., 120 days 
(see proposed Sec. 192.5(c) and section V.C of this document) is 
relatively short. To enable the agency to complete its evaluation in 
this period, it is essential that the agency have a complete notice 
when the 120-day period begins.
    The proposed timeframe for the filing decision (i.e., within 15 
working days) is consistent with the timeframe for the filing decision 
for a food additive petition (Sec. 171.1(i)(1)). The proposed process 
that ``FDA will inform the notifier'' provides flexibility for the 
mechanism whereby FDA contacts a notifier. FDA expects to contact the 
notifier by telephone or possibly by electronic mail and expects that a 
notifier would provide the missing material promptly. However, should 
circumstances warrant (e.g., FDA is unable to reach a notifier by 
telephone, or the notifier does not provide the

[[Page 4722]]

materials promptly), under the regulation, FDA could send a letter or 
telefax to the notifier explaining that the agency had received, but 
not filed, the PBN and the reasons therefor.
    Under proposed Sec. 192.30(a)(1), CFSAN will inform CVM about any 
PBN that it files. Regardless of whether the bioengineered food would 
be used in human food, food for animals, or both, this inter-Center 
communication will ensure that both Centers are aware of all 
bioengineered foods that are nearing commercialization.

B. Acknowledgment Letter

    FDA is proposing to send, within 15 working days of filing a 
notice, a letter to the notifier (or, when applicable, the notifier's 
agent) informing the notifier of the date on which FDA filed the PBN 
(proposed Sec. 192.30(b)). As a practical matter, such a letter would 
acknowledge receipt as well as inform the notifier of the date of 
filing.

C. Response Letter

    FDA is proposing to respond to a notifier within 120 days of filing 
a notice (proposed Sec. 192.30(c)). Because all submissions will be 
sent to CFSAN, CFSAN would issue the response to the notifier, 
regardless of whether the intended use of the bioengineered food is in 
human food, food for animals, or both. A response from CFSAN would make 
clear that CFSAN was aware of, and thus had been notified about, all 
bioengineered foods, regardless of their intended use.
    As with any correspondence, the particular circumstances will 
determine the full text of the agency's letter. However, the agency 
believes that a letter would likely fall into one of four general 
categories (proposed Sec. 192.30(d)(1), (d)(2), (d)(3), and (d)(4)). 
FDA discusses each of these four categories immediately below.
1. General Categories for FDA's Response
    a. Letter that extends FDA's evaluation. FDA is proposing that the 
agency could inform a notifier that the agency is extending its 
evaluation of the premarket notice by 120 days (proposed 
Sec. 192.30(d)(1)). Under the regulation, in this letter FDA would also 
inform the notifier that the agency expects that the bioengineered food 
will not be marketed during the extended evaluation period.
    Ordinarily, FDA expects to send a final response to a notifier 
within 120 days, particularly if a prospective notifier discusses 
relevant scientific and regulatory issues with FDA, prior to submitting 
a PBN about a bioengineered food (see proposed Sec. 192.10 and section 
VI of this document). However, there are several circumstances that 
could prevent the agency from completing its evaluation within that 
time period. For example, FDA may need to extend the review time if a 
notifier did not participate in the presubmission consultation program; 
the issues raised by a particular bioengineered food could be 
particularly novel and complex; parts of a submission could require 
clarification, amplification, or correction; or the submission could be 
poorly written or be of such poor scientific quality that it precludes 
timely evaluation by the agency.
    As discussed previously, FDA is issuing this proposed rule to 
ensure that it has the appropriate amount of information about 
bioengineered foods and to help to ensure that all market entry 
decisions by the industry are made consistently and in full compliance 
with the law. The goal of this rulemaking would not be achieved if a 
bioengineered food entered commercial distribution before FDA had 
completed its evaluation of the applicable notice.
    b. Letter that the notice does not provide a basis. FDA is 
proposing that the agency have an option to inform a notifier that the 
premarket notice does not provide a basis for the notifier's view that 
the bioengineered food is as safe as comparable food or is otherwise 
lawful (proposed Sec. 192.30(d)(2)). In so doing, FDA would inform the 
notifier of the reasons for this conclusion. Under the regulation, in 
this letter FDA would also inform the notifier that the agency expects 
that the bioengineered food will not be marketed.
    FDA has had experience with another food program, the proposed 
notification program for GRAS substances, in which some submitted 
notices do not provide a basis for the notifier's view that the 
intended use of a substance is lawful (Ref. 18). The underlying reasons 
why the applicable notices have not provided a basis for a GRAS 
determination have been quite varied. Likewise, there could be various 
reasons why a premarket notice does not provide a basis for the 
notifier's view that the bioengineered food is as safe as comparable 
food or is otherwise lawful. For example, the notice may not provide a 
basis for the notifier's view that a substance introduced into the 
bioengineered food is not an unapproved food additive or that the 
bioengineered food would not be misbranded. As another example, the 
notice may not provide a basis to conclude that a bioengineered food 
that contains an unusually high level of a naturally occurring toxicant 
would not be adulterated. As a third example, if the poor quality of a 
notice makes it difficult for the agency to fully evaluate the notice, 
regardless of the time period available, FDA may inform the notifier of 
the inadequacies of the notice rather than extend its evaluation of the 
notice for another 120 days.
    If a notice about a bioengineered food does not provide a basis to 
conclude that a bioengineered food is as safe as comparable food or is 
otherwise lawful, that food could be adulterated or misbranded and 
should not be marketed. If a notifier initiates commercial distribution 
of a bioengineered food after being informed that the applicable notice 
is not adequate, FDA will carefully and completely review the legal 
status of the applicable food and will use all available options to 
ensure that the food is fully in compliance with all provisions of the 
act. In particular, in such circumstances, the agency fully intends to 
bring to bear the complete range of its authorities and resources, 
including its authority under section 704 of the act (21 U.S.C. 374) to 
conduct inspections and investigations, collect samples, and perform 
analyses, as well as its authority under sections 705 and 903 of the 
act (21 U.S.C. 375 and 393) to engage in publicity and public 
education. When the agency concludes through the application of these 
resources that a food is adulterated, misbranded, or otherwise not in 
full compliance with the act, FDA will utilize the act's legal 
sanctions, as appropriate, including in rem seizure of violative foods 
and injunction proceedings against, or criminal prosecution of, those 
responsible for distributing such foods.
    c. Letter that FDA has no questions. If, based on its evaluation of 
a notice, FDA has no questions regarding the notifier's view that the 
bioengineered food is as safe as comparable food and is otherwise 
lawful, FDA would inform a notifier of that fact (proposed 
Sec. 192.30(d)(3)). Because the evaluation of food safety is a time-
dependent judgment that is based on general scientific knowledge as 
well as specific data and information about the food, FDA would qualify 
its statement to clarify that the agency has no questions ``at this 
time.'' This proposed response is similar to the letters that FDA has 
issued in response to submissions received under the 1996 procedures.
    d. Letter that a notifier has withdrawn the notice. Under proposed 
Sec. 192.20(g), if a notifier requests that FDA cease to evaluate a 
PBN, FDA would retain the PBN in its files and classify the PBN as 
``withdrawn.'' In such a circumstance,

[[Page 4723]]

FDA would bring the notification process to closure by sending the 
notifier a letter acknowledging that the agency had received a 
withdrawal letter and had ceased to evaluate the PBN, effective on the 
date that FDA received the letter (proposed Sec. 192.30(d)(4)). This 
proposed response is similar to responses issued by FDA under the 
proposed notification program for GRAS substances when the notifier 
requests that FDA cease to evaluate a GRAS notice (Ref. 18).
2. Status of the Bioengineered Food at EPA
    If the bioengineered food contains a pesticidal substance, FDA is 
proposing that FDA's response letter will describe the status of the 
bioengineered food at EPA (proposed Sec. 192.30(e)). If all applicable 
regulatory processes at EPA have come to closure (proposed 
Sec. 192.30(e)(1)), FDA would say so and would respond as described 
above. As discussed above, if regulatory processes at EPA regarding the 
bioengineered food are still pending, FDA would inform the notifier 
that FDA does not consider the PBN to satisfy the requirement for 
premarket notice (proposed Sec. 192.30(e)(2)).

X. Public Disclosure

    FDA is proposing to inform notifiers about: (1) The public 
disclosure provisions that apply to the existence and content of a PBN; 
(2) procedures that a notifier should use to inform FDA of the 
notifier's view about whether the existence or content of a PBN is 
exempt from public disclosure; and (3) the criteria that FDA uses to 
evaluate the notifier's view (proposed Sec. 192.40(a) through (d)). FDA 
also is proposing the procedures that FDA will use to disclose the 
agency's evaluation of, and response to, each PBN (proposed 
Sec. 192.40(e)). This part of the regulation would ensure that both 
notifiers and the interested public have information about provisions 
that derive from the FOIA. FDA requests comment on these proposed 
provisions. Such comments may result in a modification to the proposed 
requirements.

A. Existence of the Notice

    FDA is proposing that the existence of a filed PBN ordinarily is 
available for public disclosure on the date that FDA files it (proposed 
Sec. 192.40(a)(1)). Under the regulation, a notifier who believes that 
the existence of a PBN is exempt from disclosure would be responsible 
for asserting that claim (proposed Sec. 192.40(a)(2)). If a notifier 
claims that the existence of a PBN is confidential, FDA would evaluate 
that claim and would disclose the existence of the PBN, unless FDA 
determines that the criteria for exemption from disclosure in 
Sec. 20.61 are satisfied (proposed Sec. 192.40(a)(3)). If FDA 
determines that the existence of a PBN is confidential at the time that 
the agency files it, the existence of the PBN would become available 
for public disclosure, in accordance with Sec. 20.61, when the criteria 
for exemption from disclosure are no longer satisfied (proposed 
Sec. 192.40(a)(4)).
    FDA has previously discussed the FOIA, and the exemption from 
public disclosure that the FOIA provides for trade secrets and 
confidential commercial information, with respect to data or 
information that a developer submits to FDA during a presubmission 
consultation (section VI.B of this document). Consistent with that 
discussion, FDA believes that, in most cases, the fact that a notifier 
had submitted a PBN would not constitute confidential commercial 
information. Nevertheless, there could be circumstances in which a 
notifier submits a PBN and has grounds to claim that the existence of 
the PBN should not be available for public disclosure.
    FDA is proposing to make a list of filed PBN's easily accessible to 
the public (e.g., by placing the information on the Internet or in a 
paper or electronic file that is available at FDA for public review and 
copying) (proposed Sec. 192.40(b)). FDA expects that the list of PBN's 
would include most or all of the information in the synopsis of the 
PBN. Consistent with current procedures for updating an easily 
accessible inventory of notices received for another foods program 
(i.e., the GRAS notification program; see Ref. 18), FDA expects to 
update the list of filed PBN's on an approximately monthly basis. The 
proposed regulation to make this information easily accessible to the 
public is responsive to the input that FDA received at the public 
meetings that it convened in 1999, and to the comments that FDA 
received as a result of those meetings.

B. Content of the Notice

    FDA is proposing that the data or information in a PBN ordinarily 
are available for public disclosure on the date that FDA files the PBN 
(proposed Sec. 192.40(c)(1)). Under the regulation, a notifier who 
believes that some or all of the content of a PBN is exempt from 
disclosure would be responsible for asserting that claim (proposed 
Sec. 192.40(c)(2)). If a notifier claims that some or all of the 
content of a PBN is confidential, FDA would evaluate that claim. FDA 
would disclose the content of the PBN, unless FDA determines that the 
criteria for exemption from disclosure in Sec. 20.61 are satisfied 
(proposed Sec. 192.40(c)(3)). If FDA determines that some or all of the 
content of a PBN is confidential at the time that the agency files it, 
the data or information in question would become available for public 
disclosure, in accordance with Sec. 20.61, when the criteria for 
exemption from disclosure are no longer satisfied (proposed 
Sec. 192.40(c)(4)).\18\
---------------------------------------------------------------------------

    \18\ Section 20.61 describes both criteria for exemption from 
disclosure and procedures that apply in circumstances where FDA 
disagrees with the view of a person who submits data or information 
that some or all of those data or information satisfy the criteria 
for exemption from disclosure.
---------------------------------------------------------------------------

    Consistent with the agency's discussion of its view regarding the 
disclosability of the data or information provided to FDA during a 
presubmission consultation (section VI.B of this document), FDA 
believes that, in most cases, most of the data or information in a PBN 
would not constitute a trade secret. For example, very few of the 
submissions that FDA has received under its current consultation 
program identify specific data or information that the developer claims 
to be exempt under Sec. 20.61. However, when the existence of the PBN 
is exempt from disclosure, all data and information in the submission 
would necessarily be exempt from disclosure.
    FDA anticipates that the PBN will be easily accessible to the 
public. Under EFOIA and FDA's proposed rule to implement EFOIA, 
frequently requested records, or records that are likely to be 
requested frequently, are placed in an ``electronic reading room.'' As 
discussed above (see section VII.C of this document), FDA has 
tentatively concluded that it is likely that each submitted PBN would 
be requested under FOIA multiple times. Therefore, these records will 
be easily accessible to the public because they will be available 
electronically (proposed Sec. 192.40(d)).

C. Disclosure of FDA's Evaluation of, Response to, a Notice

    FDA is proposing to make two agency records associated with a PBN 
easily accessible to the public (e.g., by placing the information on 
the Internet or in a paper or electronic file that is available at FDA 
for public review and copying) (proposed Sec. 192.40(e)(1)). The 
applicable records include the text of the letter issued by the agency 
in response to each PBN, and the text of the agency's completed 
evaluation of each PBN.

[[Page 4724]]

    The proposed regulation commits to make available the ``text'' of 
the agency's letter and the agency's memorandum, rather than a ``copy'' 
of these records, to enable FDA to satisfy the regulations by a 
mechanism other than providing a physical copy of these records (e.g., 
by providing an electronic copy on the Internet). Consistent with 
current procedures for updating an easily accessible inventory of 
notices received for another foods program (i.e., the GRAS notification 
program; see Ref. 18), FDA expects to add the text of applicable agency 
letters and memoranda to the easily accessible file on an approximately 
monthly basis. The proposed regulation to make this information easily 
accessible to the public is responsive to the input that FDA received 
at the public meetings that it convened in 1999, and to the comments 
that FDA received as a result of those meetings.
    As discussed previously (proposed Sec. 192.30(c)(1) and section 
IX.C.1 of this document), a notifier could receive a letter that 
informs the notifier that FDA is extending its evaluation of the 
premarket notice by 120 days. Under the proposed regulation to make the 
agency's response to a PBN easily accessible to the public, such an 
extension letter would be easily accessible to the public. When FDA 
issues a final letter regarding the applicable notice, it is likely 
that the agency would replace the extension letter with the final 
letter rather than making both letters easily accessible. The fact that 
the notifier had received an extension letter would still be readily 
apparent (e.g., because the date of the final response letter would be 
more than 120 days from the date of the extension letter). In addition, 
it is likely that FDA's final response letter would acknowledge the 
fact that the agency had sent a letter extending its evaluation.

XI. Proposed Regulations Regarding Bioengineered Foods That Would 
Be Used in Animal Feed

    FDA is proposing to require the submission to the agency of data 
and information regarding bioengineered plant-derived foods that would 
be used in animal feed. FDA's proposal also includes a recommendation 
that prospective notifiers participate in a presubmission consultation 
program. In general, these proposed regulations regarding bioengineered 
foods intended to be fed to animals (proposed part 592) parallel the 
agency's proposed regulations for human food (proposed part 192). The 
following discussion addresses areas of importance in the proposed 
animal feed regulations (proposed part 592).
    The number of different species encompassed by the term ``animal,'' 
as used in the act, is extraordinarily broad. CVM has regulatory 
authority over the food consumed by all nonhuman species, ranging from 
those raised in aquaculture, such as lobster and fish, to pets, birds, 
and the traditional classes of farm animals like cattle, swine, and 
horses. These animals may consume parts of a bioengineered plant that 
are not eaten by people. For example, cattle and other herbivores eat 
the forage portion of the corn plant (stalk and leaves), which has no 
human food applications. In addition, animals may eat the byproducts or 
residues left over from the production of human foods. For example, 
soybean meal, which is a source of dietary protein widely used in 
animal diets, is a byproduct from the production of soybean oil, which 
is primarily used in human foods. As another example, broken rice, 
which is not desirable for human food, is a major pet food ingredient.
    Undesirable substances can concentrate in the byproducts or 
residues left over from the production of human foods. For example, 
gossypol, a naturally occurring toxicant in cotton, concentrates in 
cottonseed meal, which is a byproduct obtained during the manufacture 
of cottonseed oil. The presence of gossypol limits the use of 
cottonseed meal in animal feed. As another example, some substances 
that can cause enlargement of the thyroid naturally occur in rapeseed 
plants and are concentrated in the meal (commonly called canola meal) 
that is a byproduct obtained during the manufacture of low erucic acid 
rapeseed oil (comonly called canola oil). These compounds must remain 
at a low level for the canola meal to be useful in animal feed.
    In some cases, bioengineered foods could make up most of an 
animal's diet, which the animal could consume for its entire lifespan. 
For example, in a single year a high-producing dairy cow could eat as 
much as 6,000 pounds of a nutritional supplement containing added 
energy and protein. This supplement could contain up to 80 percent corn 
grain and 20 percent soybean meal. The same dairy cow could also 
consume as much as 4,380 pounds of fermented corn forage and ears 
(i.e., whole plant corn silage in that same year). Fattening beef 
cattle could eat a diet based on 10 percent whole plant corn silage, 80 
percent corn grain, and 9 percent soybean meal. A typical swine diet 
contains 74 percent corn grain and 23 percent soybean meal, while 
broiler chicks might eat a ration that is 58 percent corn grain and 35 
percent soybean meal. Because these foods may comprise such a large 
percentage of an animal's diet, an undesirable substance that is 
introduced into a bioengineered food, even at a low level, has the 
potential to adversely affect an animal that eats the food.
    Because of these factors, notifiers in assembling a PBN to address 
bioengineered foods to be consumed by animals should pay particular 
attention to the intended use of the bioengineered food, including the 
species expected to consume it; the function and level of all 
introduced or modified substances; and any changes in the composition 
and characteristics of the food. FDA has concluded that the notices 
should contain adequate information about any potential safety issues 
for all substances introduced into, or modified in, the food. Concerns 
associated with any changes in the composition or characteristics of 
the bioengineered food should also be addressed. Notifiers should be 
aware that in some cases, animal diets are formulated using different 
nutritional parameters than those used by human nutritionists. For 
example, when a diet is formulated for cattle, nutritionists utilize 
parameters such as neutral detergent fiber and acid detergent fiber in 
evaluating the suitability of a potential ingredient. Notices for 
bioengineered plants intended to be fed to animals should incorporate 
these differences in how ingredients are evaluated for their 
nutritional content.

XII. Paperwork Reduction Act

    This proposed rule contains information collection provisions that 
are subject to review by the Office of Management and Budget (OMB) 
under the Paperwork Reduction Act of 1995 (the PRA) (44 U.S.C. 3501-
3520). A description of these provisions is given below with an 
estimate of the annual reporting and recordkeeping burden. Included in 
the estimate is the time for reviewing instructions, searching existing 
data sources, gathering and maintaining the data needed, and completing 
and reviewing each collection of information.
    FDA invites comments on: (1) Whether the proposed collection of 
information is necessary for the proper performance of FDA's functions, 
including whether the information will have practical utility; (2) the 
accuracy of FDA's estimate of the burden of the proposed collection of 
information, including the validity of the methodology and assumptions 
used; (3) ways to enhance the quality, utility, and clarity of the 
information to be

[[Page 4725]]

collected; and (4) ways to minimize the burden of the collection of 
information on respondents, including through the use of automated 
collection techniques, when appropriate, and other forms of information 
technology.
    Title: Premarket Notice Concerning Bioengineered Food
    Description: Section 701 of the act sets forth authority to issue 
regulations for the efficient enforcement of the act. Section 201 of 
the act defines terms utilized within the act. Food is defined by 
section 201 of the act to mean: ``(1) articles used for food or drink 
for man or other animals, (2) chewing gum, and (3) articles used for 
components of any such article.'' Thus, the act clearly incorporates 
animal feed and drink into its definition of food.
    Section 403 of the act prohibits the misbranding of food. Section 
402 of the act prohibits the adulteration of food. Section 409 of the 
act establishes a premarket approval requirement for ``food 
additives.'' Section 201(s) of the act provides a two-step definition 
of ``food additive.'' The first step broadly includes any substance the 
intended use of which results or may reasonably be expected to result, 
directly or indirectly, in its becoming a component or otherwise 
affecting the characteristics of food, which under section 201(f) of 
the act includes animal food. The second step, however, excludes from 
the definition of food additive substances that are GRAS by qualified 
experts.
    In this proposed rule, FDA is proposing to require the submission 
to the agency of data and information regarding plant-derived 
bioengineered foods. The proposed rule refers to foods derived from 
plant varieties that are developed using rDNA technology as 
``bioengineered foods.'' FDA is proposing that this submission be made 
at least 120 days prior to the commercial distribution of such foods. 
The notice would include data and information about the bioengineered 
food and a narrative that provides an integrated discussion of those 
data and information. The notifier would maintain a record of relevant 
data and information that are not included in the notice. FDA would 
make the existence of the notice, and the agency's evaluation of and 
response to the notice, easily accessible to the public. The content of 
the notice would be publicly available consistent with the FOIA and 
other federal disclosure statutes. FDA is also proposing to include in 
the regulation a recommendation that prospective notifiers consult with 
the agency to identify and discuss relevant safety, nutritional, or 
other regulatory issues regarding a bioengineered food.
    Description of Respondents: Developers, manufacturers, 
distributors, or importers of food.
    FDA estimates the burden of this collection of information as 
follows:

                                 Table 1.--Estimated Annual Reporting Burden \1\
----------------------------------------------------------------------------------------------------------------
                                                      Annual
        21 CFR Section              No. of         Frequency per     Total Annual        Hours per       Total
                                  Respondents        Response          Responses         Response        Hours
----------------------------------------------------------------------------------------------------------------
192.10(e) through (g)                20                 1                20                 4                80
192.10(h)(1)                         20                 1                20                 0.5              10
192.10(h)(2)                         20                 1                20                 8               160
192.10(h)(3)(i)                       2                 1                 2                 2                 4
192.10(h)(3)(ii)                      2                 1                 2                 5                10
192.20(b)(2)(i)                       2                 1                 2                 2                 4
1192.20(b)(2)(ii)                     2                 1                 2                 5                10
192.20(c)(1)                         20                 1                20                 8               160
192.20(c)(2)                         20                 1                20                 8.4             168
192.20(d)                             0.5               1                 0.5              20                10
192.20(e)                             0.5               1                 0.5               2                 1
192.20(g)                             0.5               1                 0.5               1               0.5
192.20(a) through (b)(1) and         20                 1                20               190             3,800
 192.25
Total                                                                                                  4,417.50
----------------------------------------------------------------------------------------------------------------
\1\ There are no capital costs or operating and maintenance costs associated with this collection of
  information.


                               Table 2.--Estimated Annual Recordkeeping Burden \1\
----------------------------------------------------------------------------------------------------------------
   21 CFR           No. of         Annual  Frequency     Total Annual          Hours per
   Section       Recordkeepers     per Recordkeeping        Records          Recordkeeper         Total Hours
----------------------------------------------------------------------------------------------------------------
192.25(a)(2)         20                   1                  20                  19                 380
Total                                                                                              380
----------------------------------------------------------------------------------------------------------------
\1\ There are no capital costs or operating and maintenance costs associated with this collection of
  information.

    Under the proposed rule, a notifier sends a notice regarding a 
bioengineered food to CFSAN regardless of whether the intended use is 
in human food, food for animals, or both. Because FDA routinely issues 
separate regulations regarding human food and animal feed, the 
regulations associated with the notice are codified in two parts of 
title 21: part 192 and part 592. Both CFSAN and CVM have been 
consulting with developers of bioengineered foods, and have received 
submissions of data and information about such foods. Since 1994, FDA 
has received, on average, eight submissions about bioengineered foods 
that are ready for commercialization per year. However, given the 
efficiencies of rDNA techniques, the advances in these techniques, and 
the rapidly expanding information related to genomes, FDA expects that 
these techniques are likely to be utilized to an increasingly greater 
extent. Thus, for the purpose of this analysis FDA is estimating that 
the agency would receive 20 PBN's per year.
    In this analysis, FDA is assuming that all notices about 
bioengineered foods will encompass both human food and food for 
animals. FDA is making this assumption because this was the case in 
approximately 70 percent of submissions that FDA has received since 
1994. Because some 30 percent of notices may not encompass both human

[[Page 4726]]

food and food for animals, FDA's assumption results in a conservative 
estimate of the reporting and recordkeeping burden.
    Because FDA's analysis assumes that all notices will encompass both 
human food and food for animals, and because all notices are submitted 
to CFSAN, regardless of the intended use, FDA is estimating the 
recordkeeping and reporting burden only for the regulations issued in 
Part 192. FDA is making no separate estimate of the recordkeeping and 
reporting burden for the regulations issued in Part 592 because this 
burden is subsumed within the burden estimated for part 192.

A. Hourly Burden to Prepare a Report (Proposed Secs. 192.20(a) through 
(b)(1) and Sec. 192.25)

    FDA contacted five firms that had made one or more submissions 
under FDA's existing procedures, which are summarized in a guidance 
first issued in 1996 (the 1996 procedures (Ref. 5)). FDA asked each of 
these firms for an estimate of the hourly burden to prepare a 
submission under the current process. Three of these firms subsequently 
provided the requested information. Based on this information, FDA is 
estimating that the average time to prepare a submission under the 1996 
procedures is 150 hours.
    The proposed rule would include some reporting requirements that 
are not described in the 1996 procedures. After considering the amount 
of time that firms need, on average, to prepare a submission under the 
1996 procedures, and after considering the relative contribution of the 
additional parts, FDA is estimating that a firm would need 32 to 48 
additional hours to prepare the additional sections. For the purpose of 
this analysis, FDA selected the average of these estimates (i.e., 40 
additional hours).
    FDA is estimating that the hourly burden to prepare a PBN is the 
sum of the hours that a firm currently spends, on average, to prepare a 
submission under the 1996 procedures and the additional hours that a 
firm would spend, on average, to prepare a submission that addresses 
requirements that are not described under the 1996 procedures. This sum 
is 150 hours plus 40 hours, or 190 hours.

B. Hourly Reporting Burden Associated With Confidential Information in 
a Report (Proposed Sec. 192.20(b)(2)(i) and (b)(2)(ii)

    FDA expects that most of the data or information in a PBN will be 
available for public disclosure. However, a few firms that made 
submissions under the 1996 procedures included information that they 
considered to be confidential. To ensure that FDA is aware of 
confidential information, under the proposed rule a notifier must 
identify any confidential information in the PBN. FDA is estimating 
that two PBN's per year would contain confidential information and that 
it would take a notifier 2 hours to identify this information. Under 
the proposed rule, a notifier who includes confidential information 
must prepare and submit an additional paper copy that has been edited 
to delete confidential information (i.e., a redacted copy). FDA is 
estimating that it would take a notifier 5 hours to prepare the 
redacted copy. FDA's estimates of the hourly reporting burden 
associated with confidential information are based on its familiarity 
with submissions received under the 1996 procedures, including the 
content and organization of those submissions. In most cases, the 
confidential information is present in limited locations within a given 
submission.

C. Hourly Reporting Burden Associated With Electronic Copies of the 
Report (Proposed Secs. 192.20(c)(1) and (c)(2)

    Under the proposed rule, a notifier ordinarily would submit an 
electronic copy that would be in a format that is suitable for FDA to 
use to make the PBN available in an electronic reading room (e.g., html 
format). FDA is estimating that it would take 8 hours to format the 
electronic disclosure copy. Because a notifier who includes 
confidential information must redact this copy, FDA is estimating that 
it would take an additional 4 hours to do the redacting and that this 
would occur in 2 of the 20 notices submitted per year. Thus, FDA is 
estimating that it would take a total of 8.4 hours, on average, to 
prepare the electronic disclosure copy. FDA's estimate of the hourly 
reporting burden associated with an electronic copy is based on its 
understanding of the attributes of commonly used software programs that 
likely would be used to prepare the electronic copy.
    Under the proposed rule, a notifier may request a waiver from the 
proposed requirement to submit an electronic disclosure copy, e.g., 
because the notifier does not have access to the technology that is 
needed to prepare such a copy. Because a notifier who requests a waiver 
need only write an explanation of why he is requesting the waiver, FDA 
estimates that it would take 0.5 hours to request a waiver. Because 
most firms who have already consulted with FDA regarding bioengineered 
foods are large firms who likely would have access to the appropriate 
technology, FDA is assuming that a request for a waiver will be a rare 
event, and may not happen at all. Therefore, in this estimate of the 
hourly burden to prepare a notice, FDA is making the conservative 
assumption that all firms will submit an electronic disclosure copy, 
with an hourly burden of 8 hours, and that no firms will request a 
waiver, which would have a reduced burden of only 0.5 hours.
    In addition, in the proposed rule FDA is recommending that a 
notifier submit an electronic copy that would be formatted in a manner 
that is suitable for FDA to use to evaluate the PBN (e.g., portable 
document format (PDF)). A notifier who submits an electronic evaluation 
copy would submit one less paper copy. FDA is estimating that it would 
take 8 hours to format the electronic evaluation copy.

D. Hourly Reporting Burden Associated With English Language 
Translations, Authorization to Incorporate Information by Reference, 
and Withdrawal (Proposed Sec. 192.20(d), (e), and (g)

    Under the proposed rule, a notifier who includes information in a 
foreign language must include an English translation that is verified 
to be accurate and complete. Based on its experience, FDA is estimating 
that it would take 20 hours to prepare such a translation and that this 
would happen very rarely (i.e., once every 2 years). However, FDA has 
limited experience with the hourly burden associated with English 
language translations and specifically requests comment on this 
estimate.
    Under the proposed rule, a notifier who wishes to incorporate by 
reference a submission made by another party must include a signed 
statement from that party, authorizing the notifier to incorporate the 
information by reference, unless the referenced submission is publicly 
available (e.g., under the FOIA). FDA is estimating that it would take 
2 hours to obtain the signed statement and that this would happen very 
rarely (i.e., once every 2 years). FDA's estimate is based on its 
experience with incorporation by reference in another food program 
(i.e., the food additives program).
    Under the proposed rule, a notifier who wishes to withdraw a PBN 
from FDA's consideration must do so in writing. Because this can be 
done by a simple letter, FDA is estimating that it would take 1 hour. 
FDA also is estimating that this would happen very rarely (i.e., once 
every 2 years).

[[Page 4727]]

E. Hourly Reporting Burden Associated With a Voluntary Presubmission 
Consultation Program (Proposed Sec. 192.10(e) through (g), (h)(2), 
(h)(3)(i), and (h)(3)(ii)

    In the proposed rule, FDA is recommending that prospective 
notifiers participate in a presubmission consultation program. 
Accordingly, FDA has estimated the hourly burden to notifiers who 
choose to participate.
    Under the proposed rule, a prospective notifier who requests 
consultation prepares a single submission to address potential uses of 
the bioengineered food in both human food and food intended for 
animals. The prospective notifier would send multiple paper copies of 
the submission to CFSAN, who would contact CVM when the bioengineered 
food would be consumed by animals. Based on its experience under the 
1996 procedures, FDA is estimating that it would take 0.5 hours to 
prepare the multiple copies that would be submitted for each request 
for consultation.
    Since 1994, FDA has received on average approximately seven 
requests per year for consultation about bioengineered foods that are 
under development (i.e., before the foods are ready for 
commercialization). However, given the efficiencies of rDNA techniques, 
the advances in these techniques, and the rapidly expanding information 
related to genomes, FDA expects that these techniques are likely to be 
utilized to an increasingly greater extent. For the purpose of this 
analysis FDA is estimating that the agency would receive 20 requests 
for consultation per year about bioengineered foods. Based on its 
experience under the 1996 procedures, FDA is estimating that it would 
take 4 hours to prepare written materials that accompany the original 
request for consultation and 8 hours to prepare one or several 
additional written submissions as the consultation proceeds.
    To ensure that FDA is aware of confidential information, a notifier 
who submits confidential information must both identify the 
confidential information and prepare and submit an additional paper 
copy that does not contain such information. FDA is estimating that it 
would take 2 hours to identify such information in both the original 
and additional submissions and that it would take 5 hours to prepare 
redacted copies of these submissions. FDA also is estimating that 
approximately 2 of 20 requests for consultation would include 
confidential information. FDA's estimates are based on its familiarity 
with requests for consultation under the 1996 procedures, including the 
content and organization of written materials that accompanied those 
requests.

F. Hourly Recordkeeping Burden (Proposed Sec. 192.25(a)(2))

    Under the proposal, notifiers must retain the data and other 
information that provides the basis for their conclusions about the 
bioengineered food. FDA is assuming that notifiers would establish and 
maintain an administrative file that contains these data and 
information. Based on its experience with the content of submissions 
received under the 1996 procedures, FDA is estimating that the one-time 
process of establishing such a file would equal 10 percent of the 
hourly burden already estimated for preparing a PBN (i.e., 10 percent 
of 190 hours, or 19 hours).
    In compliance with the PRA, the agency has submitted the 
information collection provisions of this proposed rule to OMB for 
review. Interested persons must submit written comments regarding 
information collection by February 20, 2001, to the Office of 
Information and Regulatory Affairs, OMB, New Executive Office Bldg., 
725 17th St. NW., rm. 10235, Washington, DC 20503, Attn: Desk Officer 
for FDA.

XIII. Analysis of Economic Impacts

A. Cost-Benefit Analysis

    FDA has examined the economic implications of this proposed rule as 
required by Executive Order 12866. 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). Executive Order 12866 classifies a 
rule as significant if it meets any one of a number of specified 
conditions, including: having an annual effect on the economy of $100 
million, adversely affecting a sector of the economy in a material way, 
adversely affecting competition, or adversely affecting jobs. A 
regulation is also considered a significant regulatory action if it 
raises novel legal or policy issues. The Office of Management and 
Budget has determined that this proposed rule is a significant 
regulatory action as defined by Executive Order 12866.

B. Background

    Bioengineered foods have the potential to offer multiple benefits 
such as: Improved yield, drought resistance, disease resistance, 
improved flavor, longer shelf life, increased nutrition, and reduced 
need for pesticides, among others. Consumers have expressed concern, 
however, about possible risks that can accompany bioengineered foods. 
From a public health perspective, the main concerns are allergenicity 
and toxicity. To ensure that bioengineered foods are as safe as their 
conventional counterparts, FDA instituted a consultation process with 
industry to review the development of new bioengineered foods (57 FR 
22984 at 22991 and (Ref. 5)). Since then, food producers have completed 
some 45 consultations about bioengineered foods. To the best of our 
knowledge all bioengineered foods on the market have gone through FDA's 
process before they have been marketed.
    Under the current process, a developer who intends to commercialize 
a bioengineered food meets with the agency prior to marketing to 
identify and resolve relevant safety, nutritional, or other regulatory 
issues regarding the bioengineered food. When the developer believes 
that it has accumulated adequate data or information to address and 
resolve any potential safety or other regulatory issues, the developer 
submits to FDA a summary of its assessment of these issues. Agency 
scientists evaluate that summary to determine whether any safety or 
other regulatory issues are resolved. This process ensures that 
developers of bioengineered foods are aware of and address safety and 
other issues prior to marketing.
    However, because the consultation process is voluntary, food 
producers could choose not to notify FDA. Additionally, as food 
producers in countries that export foods to the United States begin to 
adopt bioengineered varieties, they may choose not to participate in 
the voluntary consultation process. Requiring premarket notification 
for bioengineered foods ensures that FDA will continue to have the 
opportunity to discuss safety and other regulatory issues with 
developers before new bioengineered foods go on the market, thereby 
putting an additional check in place for bioengineered foods.
1. Benefits
    Although the current consultation process has been successful in 
that the agency believes that it has reviewed all of the bioengineered 
foods that have reached the market, a firm could bypass the current 
review process. In so doing, the firm may market a product that 
presents safety or other regulatory issues

[[Page 4728]]

that would otherwise have been identified and resolved through 
consultation with the agency. For example, the food may contain an 
unexpected allergen or an unapproved food additive, or may be so 
significantly different from its conventional counterpart that special 
labeling would be required to enable consumers to identify the 
difference.
    Bioengineering enables developers to expand greatly the range of 
sources of genes to introduce into foods. Genes code for proteins, and 
virtually all known food allergens are proteins. Therefore, by 
transferring a gene from one foodplant to another (and thereby 
essentially transferring a protein from one food to another) one may 
transfer the allergenic properties of the first food to the second. 
Because food allergies can result in serious harm, including 
anaphylactic shock and death, it is important to know the allergenic 
profile of food from a plant that is to be used as the source of a gene 
to be transferred to another foodplant.
    It is also possible for a protein that has never been in food 
before to become an allergen once people become exposed to it in the 
diet. Therefore, it is also important to know whether a protein from a 
traditionally nonfood source has characteristics associated with 
allergenic proteins.
    Similarly, because bioengineering enables developers to introduce 
genetic material from a wider range of sources than has traditionally 
been possible, there is a greater likelihood that a developer using 
bioengineering to modify a foodplant may introduce genetic material 
whose expression results in a substance that is significantly different 
from substances historically consumed in food. Such a substance may 
require premarket approval as a food additive because it may not be 
GRAS.
    It is also possible with bioengineering that the newly introduced 
genetic material may be inserted into the chromosome of a foodplant in 
a location that causes the food derived from the plant to have higher 
levels of toxins than normal, or lower levels of a significant 
nutrient. In the former case, the food may not be safe to eat, or may 
require special preparation to reduce or eliminate the toxic substance. 
In the latter case, the food may require special labeling, so that 
consumers would know that they were not receiving the level of 
nutrients they would ordinarily expect from consuming a comparable 
food. It is important therefore for developers to evaluate 
bioengineered foods from new plant varieties to determine whether the 
composition of the food has been altered.
    The additional provisions of the proposed rule, beyond what was 
requested by the 1996 procedures, aid in ensuring that relevant safety 
questions are addressed by the developer. The submission of a narrative 
of the developer's reasons for concluding that the bioengineered food 
is as safe as comparable food and its justification of the choice of 
comparable foods by the notifier will aid in ensuring that all 
potential safety issues have been considered. Discussion of unsuitable 
uses will provide FDA the opportunity to ensure that foods that would 
not be suitable for particular applications are not marketed for those 
applications. Submission of a redacted copy will aid the agency in 
protecting confidential information in the notice and in responding to 
FOIA requests. Submission of an electronic disclosure copy would 
facilitate the agency's making the PBN available in an electronic 
reading room.
2. Costs
    For developers who would have gone through FDA's consultation 
process, the costs associated with the proposed required process would 
include only costs of the additional provisions of the proposed rule. 
The required process will be modeled on the experience and knowledge 
gained from the current consultation process, but there will be a 
number of new provisions that will have costs for notifiers. First, the 
rule would require a narrative explaining how the notifier concluded 
the bioengineered food is as safe as comparable food and that the food 
is in compliance with the act. Second, notifiers who inform FDA about a 
bioengineered food that contains a gene that encodes resistance to an 
antibiotic must specifically discuss the issues associated with the use 
of that gene. Although this provision was not in the 1992 policy or the 
1996 procedures, in 1998 FDA released draft guidance for public 
comment. Since 1998, most notifiers who are in this situation have 
included this discussion in their submissions; in addition, many plant 
varieties are being developed without genes that encode resistance to 
an antibiotic. Therefore, FDA is considering that the requirement to 
discuss genes that encode resistance to an antibiotic be a cost of the 
proposed rule for only one submission per year (that is, FDA is 
estimating that only one relevant submission would have omitted this 
discussion without the rule). Third, notifiers must submit a written 
justification of their choice of foods that are comparable to the 
bioengineered food and the historic uses of these comparable foods. 
Fourth, if the bioengineered food is unsuitable for any applications or 
uses, notifiers must submit a description of these applications or 
uses. Because inappropriate uses are seldom an issue, FDA is 
considering that this issue would arise approximately once every 3 
years. Fifth, if the submission includes confidential information, 
notifiers must submit redacted copies. Because very few submissions 
under the current process have included confidential information, FDA 
is considering that approximately one or two copies per year will 
contain confidential materials. Sixth, notifiers must ordinarily would 
submit an electronic copy suitable for making the PBN available in an 
electronic reading room, but could request a waiver if they have access 
to the technology that would be needed to prepare the copy.
    FDA contacted five firms that had made one or more submissions 
under the 1996 procedures. FDA asked each of these firms for an 
estimate of the hourly cost associated with preparing a submission 
under the current process. Three of these firms subsequently provided 
the requested information. One firm estimated an average cost of $125 
per hour; another firm estimated an average cost of $48 per hour; a 
third firm estimated an average cost of $60 per hour. Based on this 
information, FDA is estimating that the average cost to prepare a 
submission under the 1996 procedures is approximately $78 per hour.
    The agency estimated the cost of a notice as the time needed 
multiplied by $78, the average cost associated with the person 
responsible for preparing a notice. Since 1994, FDA has received 
approximately eight submissions per year, but the agency expects this 
number of submissions to increase because of the increasing use of the 
technology. Because most firms who have consulted with FDA under the 
current process are large firms who likely would have access to the 
technology that would be needed to prepare an electronic disclosure 
copy, in this analysis FDA is estimating that no firms would request a 
waiver from the proposed requirement to submit such a copy. Therefore, 
total costs for these additional provisions are expected to be between 
$16,604 and $67,444 per year.

[[Page 4729]]



                                                                                            Table 3.
------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
                                                                                                 Time costs per submission
                                                            Number of submissions per year                (hours)                     Cost per submission               Total annual cost
------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
Narrative                                                  8 to 20                           8 to 16                           $624 to $,1248                    $4992 to $24960
Antibiotic resistance                                      1 to 2                            8 to 16                           $624 to $1248                     $624 to $2496
Comparable foods                                           8 to 20                           8 to 16                           $624 to $1248                     $4992 to $24960
Unsuitable uses                                            1/3                               8 to 16                           $624 to $1248                     $208 to $416
Electronic disclosure copy                                 8 to 20                           8.4                               $655                              $5242 to $13104
Redacted paper copy                                        1 to 2                            7                                 $546                              $546 to $1092
------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------

    For developers who would not have chosen to notify FDA, the cost of 
the proposed rule would be higher. Regardless of whether they choose to 
consult with FDA, food producers are statutorily prohibited from 
marketing misbranded or adulterated foods. To ensure that the new food 
is not adulterated or misbranded, the developer must generate similar 
information to what would be required under the proposed notification 
requirement. Therefore, for these developers, the cost of the proposed 
notification requirement would be the submission of paperwork 
documenting the generation of the needed information, not the 
information itself. FDA's estimate of the time required to prepare a 
notice is discussed previously (section XII of this document). 
According to that analysis, the average submission would require 255.5 
hours of preparation. Additionally, maintaining records of the notice 
would require 19 hours by the firm. At an average hourly cost of $78, 
the total cost of preparation and recordkeeping for a submission would 
be $21,411 (hourly cost x 274.5 hours).
    As discussed above, FDA has requested comment on whether this rule 
should also include a requirement that a premarket notice for a 
bioengineered food include methods by which the food could be detected. 
As part of its analysis of impacts, FDA requests comments on the 
technical feasibility and if feasible, the costs of requiring such 
methods in a PBN. In particular, FDA requests comments on the 
feasibility and costs of requiring methods of detection in all 
circumstances and in a limited set of circumstances, such as foods 
whose use is restricted in some way. FDA also requests comments on the 
costs of supplying methods for detection of the bioengineered food in 
crops and in finished food products.

C. Regulatory Flexibility Act

    FDA has examined the economic implications of this proposed rule as 
required by the Regulatory Flexibility Act (5 U.S.C. 601-612). If a 
rule has a significant economic impact on a substantial number of small 
entities, the Regulatory Flexibility Act requires agencies to analyze 
regulatory options that would lessen the economic effect of the rule on 
small entities.
    Businesses in Agricultural Services are considered small if they 
have fewer than 500 employees, and in Commercial Physical and 
Biological Research (SIC 8731) if they have less than $5 million in 
annual receipts. Companies engaged in the development of bioengineered 
food may fit into either of these categories. Since 1994, more than 45 
biotechnology submissions have been completely evaluated by FDA; these 
submissions were made by 11 distinct companies and 3 universities. Most 
of these companies are multinationals with hundreds of millions of 
dollars in annual sales and do not meet the criteria for a small 
entity. However, at least one of the companies that has notified FDA 
would meet the small entity definitions.
    For firms that would not have notified FDA, the cost may be 
$21,411. FDA finds that this proposed rule would have a significant 
economic impact on a substantial number of small entities.
    FDA considered a number of options to ease the burden on small 
businesses. Extra flexibility for small businesses meeting with FDA was 
considered. However, the proposed rule as written already includes 
flexibility for meeting with FDA, allowing phone meetings in lieu of 
meeting in person. Additional guidance was another option considered. 
However, the recommended presubmission consultation provides an 
opportunity for small businesses to get guidance from FDA about 
regulatory and safety concerns and how they can be dealt with by a 
small business. Thus, FDA has tentatively determined there is adequate 
flexibility written into the rule to accommodate the special needs of 
small businesses.

D. Unfunded Mandates Reform Act

    Section 202(a) of the Unfunded Mandates Reform Act of 1995 (Public 
Law 104-4) requires that agencies prepare a written statement of 
anticipated costs and benefits before proposing any rule that may 
result in an expenditure by State, local, and tribal governments, in 
the aggregate, or by the private sector, of $100 million in any one 
year (adjusted annually for inflation). FDA has tentatively determined 
that this proposed rule is not a significant action as defined in the 
Unfunded Mandates Reform Act and will not have an effect on the economy 
that exceeds $100 million adjusted for inflation in any one year. The 
correct inflation-adjusted statutory threshold is $107 million.

XIV. Effective Date

    FDA proposes that any final rule that may issue based on this 
proposal become effective 60 days after the date of publication of the 
final rule in the Federal Register.

XV. Environmental Impact

    The agency has determined under 21 CFR 25.30(h) that this action is 
of a type that does not individually or cumulatively have a significant 
effect on the human environment. Therefore, neither an environment 
assessment nor an environmental impact statement is required.

XVI. Comments

    Interested persons may submit to the Dockets Management Branch 
(HFA-305), Food and Drug Administration, 5630 Fishers Lane, rm. 1061, 
Rockville, MD 20852, written comments regarding this proposal by April 
3, 2001. Submit written comments on the information collection 
provisions by February 20, 2001. 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 Dockets 
Management Branch between 9 a.m. and 4 p.m., Monday through Friday.

XVII. 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.

[[Page 4730]]

    1. Transcript of the Meeting of FDA's Food Advisory Committee, 
Herndon, VA, April 6, 7, and 8, 1994.
    2. Transcript of the Joint Meeting of FDA's Food Advisory 
Committee and Veterinary Medicine Advisory Committee, November 2 and 
3, 1994.
    3. Table of Contents, ``Toxicological Principles for the Safety 
Assessment of Direct Food Additives and Color Additives Used in 
Food'' (Also known as ``Redbook I''), FDA, Bureau of Foods (Now 
CFSAN), 1982. May be Purchased From: National Technical Information 
Services (NTIS), 5285 Port Royal Rd., Springfield, VA 22161, 703-
487-4650, NTIS Order Number PB83-170696.
    4. Table of Contents, ``Toxicological Principles for the Safety 
of Food Ingredients; Redbook 2000,'' available at http://vm.cfsan.fda.gov.
    5. ``Guidance on Consultation Procedures: Foods Derived From New 
Plant Varieties,'' available at http://vm.cfsan.fda.gov.
    6. ``Foods Derived From New Plant Varieties Derived Through 
Recombinant DNA Technology; Final Consultations Under FDA's 1992 
Policy,'' available at http://vm.cfsan.fda.gov.
    7. Press Release, U.S. Department of Health and Human Services, 
``FDA to Strengthen Pre-market Review of Bioengineered Foods,'' May 
3, 2000, available at http://vm.cfsan.fda.gov.
    8. Transcripts from Public Meetings Held on November 18, 1999, 
Chicago, IL, November 30, 1999, Washington, DC, and December 13, 
1999, Oakland, CA; at http://www.fda.gov.
    9. Nordlee, J. A. et al., ``High Methionine Brazil Nut Protein 
Binds Human IgE,'' Journal of Allergy and Clinical Immunology, vol. 
93, number 1, part 2, p. 209, 1994.
    10. Nordlee, J. A. et al., ``Identification of Brazil-Nut 
Allergen in Transgenic Soybeans,'' New England Journal of Medicine, 
vol. 334, pp.688-728, 1996.
    11. Ye, X. et al., ``Engineering the Provitamin A (Beta-
Carotene) Biosynthetic Pathway into (Carotenoid-Free) Rice 
Endosperm,'' Science vol. 287: pp. 303-05, 2000.
    12. Kubo, Tomoaki, ``Potential of Foods From Which Unfavorable 
Component Have Been Removed,'' Topic 10, Joint FAO/WHO Expert 
Consultation on Foods Derived from Biotechnology, Biotech 00/12, 29 
May-2 June 2000, available at www.who.int/fsf/GMfood/consultation) 
May2000/biotech) 00) 12.pdf.
    13. Agriculture Biotechnology: Permitting, Notification, and 
Deregulations, U.S. Department of Agriculture, Animal Plant Health 
and Inspection Service, available at http://www.aphis.usda.gov.
    14. Genetically Modified Pest-Protected Plants: Science and 
Regulation. Committee on Genetically Modified Pest-Protected Plants, 
Board on Agriculture and Natural Resources, National Research 
Council, National Academy Press, Washington, DC 20055, available at 
http://www.nap.edu/.
    15. ``Guidance for Industry: Use of Antibiotic Resistance Marker 
Genes in Transgenic Plants,'' available at http://vm.cfsan.fda.gov.
    16. ``Report on Consultations Regarding Use of Antibiotic 
Resistance Marker Genes in Transgenic Plants,'' available at http://vm.cfsan.fda.gov.
    17. Transcript of ``Conference on Scientific Issues Related to 
Potential Allergenicity in Transgenic Food Crops,'' Annapolis, MD, 
April 18 and 19, 1994, Document TR-1, summary available at http://vm.cfsan.fda.gov.
    18. Inventory of GRAS Notices, available at http://vm.cfsan.fda.gov.

List of Subjects

21 CFR Part 192

    Administrative practice and procedure, Food additives, Food 
labeling, Foods, Reporting and recordkeeping requirements.

21 CFR Part 592

    Administrative practice and procedure, Animal feeds, Animal foods, 
Food additives, Food labeling, Reporting and recordkeeping 
requirements.

    Therefore, under the Federal Food, Drug, and Cosmetic Act and under 
authority delegated to the Commissioner of Food and Drugs, it is 
proposed that Title 21 CFR, Chapter I be amended as follows:
    1. Add part 192 to read as follows:

PART 192--PREMARKET NOTICE CONCERNING BIOENGINEERED FOOD

Sec.
192.1  Definitions: What terms do I need to know?
192.5  Requirement for premarket biotechnology notice.
192.10  Recommendation for presubmission consultation.
192.20  Premarket biotechnology notice: Administrative information.
192.25  Premarket biotechnology notice--required parts: What must I 
include in a premarket biotechnology notice?
192.30  FDA evaluation and response: What will I get back from FDA 
and how long will it take?
192.40  Public disclosure.


    Authority: 21 U.S.C. 331, 342, 343, 348, 371.

PART 192--PREMARKET NOTICE CONCERNING BIOENGINEERED FOOD


Sec. 192.1  Definitions: What terms do I need to know?

    (a) A bioengineered food means food derived from a plant that is 
developed using a transformation event.
    (b) Commercial distribution means introduction, or delivery for 
introduction, into interstate commerce for sale or exchange for 
consumption in any form by humans or other animals.
    (c) A notifier is the person who submits a premarket biotechnology 
notice under this part. Any person who is responsible for the 
development, distribution, importation, or sale of a bioengineered food 
may be a notifier.
    (d) A premarket biotechnology notice (PBN) is a submission to FDA 
regarding a bioengineered food that is intended to enter commercial 
distribution. Under this part, a PBN includes all data and information 
in the original submission and in any amendments to the original 
submission.
    (e) Transformation event means the introduction into an organism of 
genetic material that has been manipulated in vitro. For the purpose of 
this part, ``organism'' refers to plants.


Sec. 192.5  Requirement for premarket biotechnology notice.

    (a) What foods must I notify FDA about? You must notify FDA about 
any bioengineered food, including a bioengineered food derived from a 
new plant variety modified to contain a pesticidal substance, that will 
enter commercial distribution unless all of the following conditions 
are satisfied:
    (1) The bioengineered food derives from a plant line that 
represents a transformation event that has been addressed in a PBN 
previously submitted to FDA;
    (2) The use or application of the bioengineered food has been 
addressed in a notice previously submitted to FDA; and
    (3) A letter from FDA demonstrates that FDA has evaluated the use 
or application of the bioengineered food and has no questions about it. 
This would include a letter issued between May 1, 1994, and the 
effective date of this rule.
    (b) Must the data or other information that I submit to support my 
PBN be generated from a particular plant line? The data or other 
information that you submit to FDA regarding a bioengineered food must 
be generated from a plant line whose derivation can be traced to the 
transformation event that is the subject of the notice and that 
contains the genetic material introduced via the transformation event.
    (c) When do I submit my PBN? You must submit your PBN at least 120 
days before the bioengineered food is marketed.


Sec. 192.10  Recommendation for presubmission consultation.

    (a) Is there a program that provides an opportunity for me to 
consult with FDA about a bioengineered food before I submit a PBN? FDA 
has established a presubmission consultation program to enable a 
prospective notifier to identify and discuss relevant safety, 
nutritional, or other issues regarding a bioengineered food before 
submitting a PBN about that food. FDA recommends that you participate 
in this program.

[[Page 4731]]

    (b) How does the presubmission consultation program work? In this 
program, you inform FDA about the bioengineered food. FDA encourages 
you to discuss with us safety, nutritional, or other issues that may be 
associated with the bioengineered food. FDA will establish an 
administrative file for your consultation. Although FDA may provide 
written feedback during the consultation, that feedback would not 
release you from the requirement in Sec. 192.5 to notify FDA about the 
bioengineered food as described in Secs. 192.20 and 192.25.
    (c) Would the fact that I am consulting with FDA be confidential? 
(1) In most cases, the fact that you are consulting with FDA would not 
be confidential.
    (2) If you claim that the fact that you are consulting with FDA is 
confidential, FDA will evaluate your claim. If FDA is asked, under the 
Freedom of Information Act (FOIA), about whether you are consulting 
with us, FDA will disclose that fact unless we determine that your 
claim demonstrates that the criteria for exemption from disclosure in 
Sec. 20.61 of this chapter are satisfied.
    (d) Would any of the data or other information in the 
administrative file of my consultation be disclosed to the public? (1) 
If the fact that you are consulting with FDA is not confidential, then 
the data or other information in the administrative file of your 
presubmission consultation would be available for public disclosure in 
accordance with Sec. 20.61 of this chapter.
    (2) As long as the fact that you are consulting with FDA is 
confidential, then the data or other information in the administrative 
file of your presubmission consultation would not be available for 
public disclosure.
    (e) How do I get started? To participate in the presubmission 
consultation program, write to FDA and tell us that you want to consult 
about a bioengineered food.
    (f) If I participate, what do I provide to FDA? (1) You must state 
your view as to whether the fact that you are consulting with FDA, or 
any or all of the data or other information that you submit to FDA, is 
exempt from disclosure under the FOIA (i.e., is confidential).
    (2) If you claim that the fact that you are consulting with FDA, or 
that any or all of the data or other information that you submit to FDA 
is confidential, you must explain the basis for your claim.
    (3) We recommend that you send us the following synopsis about the 
requested consultation:
    (i) Your name and address;
    (ii) The name of the bioengineered food that is the subject of the 
presubmission consultation and the plant species from which it is 
derived;
    (iii) The distinctive designation(s) that you use to identify the 
applicable transformation event(s);
    (iv) A list of the identity(ies) and source(s) of introduced 
genetic material;
    (v) A description of the purpose or intended technical effect of 
the transformation event. This includes expected significant changes in 
the composition or characteristic properties of food derived from the 
plant as a result of the transformation event, regardless of whether 
these changes result from the insertion of new genes or from a 
modification in the expression of endogenous genes;
    (vi) A description of the intended applications or uses of the 
bioengineered food; and
    (vii) A description of any applications or uses that are not 
suitable for the bioengineered food.
    (g) Where do I send my written request for consultation? Send your 
written request for consultation about a bioengineered food to the 
Office of Premarket Approval (HFS-200), Center for Food Safety and 
Applied Nutrition, 200 C St. SW., Washington, DC 20204. As necessary 
and appropriate, the Center for Food Safety and Applied Nutrition 
(CFSAN) will coordinate FDA's evaluation of your request with the 
Office of Surveillance and Compliance, Center for Veterinary Medicine 
(CVM).
    (h) What copies do I send? (1) You should send an original and at 
least two paper copies of your written request for consultation.
    (2) If you submit additional written information to FDA (i.e., 
after your original written request), you should send an original and 
at least two paper copies of each additional submission.
    (3) If you claim that any specific data or other information that 
you provide to FDA during the consultation are confidential, you 
should:
    (i) Clearly identify, in each submission, the data or other 
information that you claim are confidential;
    (ii) Prepare and submit a ``redacted'' paper copy of the submission 
(i.e., a copy that does not contain any of those data or information).
    (iii) Prepare this redacted paper copy in a manner that clearly 
identifies the location and relative size of deleted information.
    (i) What will FDA do with my written request for consultation? (1) 
FDA will establish an administrative file for your consultation and 
will place the following materials in that file:
    (i) Any correspondence between you and FDA;
    (ii) Any written materials that you provide during the consultation 
process; and
    (iii) A memorandum of each meeting or significant phone call that 
you have with FDA regarding the subject of your consultation.
    (2) If you ask FDA to discuss the bioengineered food with you, we 
will do so (e.g., at a meeting at its offices or via a telephone 
conference).


Sec. 192.20  Premarket biotechnology notice: Administrative 
information.

    (a) Where do I send my PBN? Send a PBN regarding a bioengineered 
food to the Office of Premarket Approval (HFS-200), Center for Food 
Safety and Applied Nutrition, Food and Drug Administration, 200 C St. 
SW., Washington, DC 20204. As necessary and appropriate, the Center for 
Food Safety and Applied Nutrition (CFSAN) will coordinate FDA's 
evaluation of your PBN with the Office of Surveillance and Compliance, 
Center for Veterinary Medicine (CVM).
    (b) What paper copies do I send? (1) At a minimum, you must submit 
an original paper version and one paper copy of a PBN (including any 
amendments that you make to your PBN). The original paper version will 
be the official version at FDA. If, under paragraph (c)(1) of this 
section, you choose not to send an electronic evaluation copy of your 
PBN, then you must submit one additional paper copy, for a total of 
three paper copies.
    (2) If you claim that specific data or other information in the PBN 
are confidential, you must:
    (i) Clearly identify, in each submission, the data or information 
that you claim are confidential;
    (ii) Prepare and submit a ``redacted'' paper copy of the PBN (i.e., 
a copy that does not contain any of those data or information); and
    (iii) Prepare this redacted paper copy in a manner that clearly 
identifies the location and relative size of deleted information.
    (c) What electronic copies do I send? (1) Evaluation copy. FDA 
recommends that you submit an electronic copy that is formatted in a 
manner that makes it suitable for FDA to use while evaluating your PBN. 
If you do so, you should submit such an electronic copy of your 
original PBN and of any amendments that you make to your PBN. To obtain 
current information about the technical format of this evaluation copy, 
contact the Office of Premarket Approval (OPA)

[[Page 4732]]

at the address listed previously or look on OPA's home page on the 
Internet.
    (2) Disclosure copy. (i) Unless waived under paragraph (c)(2)(ii) 
of this section, you must submit an electronic copy that is formatted 
in a manner that makes it suitable for FDA to use to make your PBN 
available to the public in an electronic reading room. This includes an 
electronic copy of your original PBN and of any amendments that you 
make to your PBN. If you claim that specific data or other information 
in the PBN are confidential, you must remove such data or information 
from the disclosure copy in a manner that clearly identifies the 
location and relative size of deleted information. To obtain current 
information about the technical format of this disclosure copy, write 
to OPA at the address listed previously or look on OPA's home page on 
the Internet.
    (ii) You may request that FDA waive the requirement for an 
electronic disclosure copy, e.g., if you do not have access to the 
appropriate technology for formatting such a copy. FDA will grant or 
deny your request according to its merits.
    (d) May I submit any data or other information, such as a reprint 
of a published scientific article, in a foreign language? If you submit 
any material in a foreign language, you must provide an English 
translation that is verified to be complete and accurate.
    (e) May I incorporate data or other information that are already 
retained in FDA's files by referring to them? (1) If you previously 
submitted a file to FDA, you may incorporate that file by referring FDA 
to it.
    (2) If someone else previously submitted a file to FDA, the 
procedure that you may use to incorporate that file into your PBN 
depends on whether the file is publicly available (e.g., the file is in 
an electronic reading room or is otherwise available under FOIA).
    (i) If the file is publicly available, you may incorporate that 
file by referring FDA to it.
    (ii) If the file is not publicly available, you may incorporate 
that file by referring FDA to it if the person who submitted the file 
authorizes you to do so in a signed statement and you include that 
signed statement in your PBN.
    (f) How can I get additional information that will help me to 
prepare a PBN? You can obtain current guidance regarding specific 
technical issues by writing to OPA at the address listed previously or 
by looking on OPA's home page on the Internet.
    (g) May I withdraw a PBN from FDA consideration after I send it? 
(1) At any time during FDA's evaluation of a PBN, you may request that 
FDA cease to evaluate it. Your request would not preclude you from 
submitting a future PBN about the same bioengineered food.
    (2) If you request that FDA cease to evaluate your PBN, FDA will 
retain your PBN in its files and classify your PBN as ``withdrawn.''


Sec. 192.25  Premarket biotechnology notice--required parts: What must 
I include in a premarket biotechnology notice?

    A PBN has seven parts. You must include all of the information 
described in each part, or explain why it does not apply to the 
bioengineered food.
    (a) Part I. In your PBN, you must provide a letter that a 
responsible official of your organization, or your attorney or agent, 
dates and signs. In this letter, you inform FDA that you are submitting 
a PBN under Sec. 192.25, state your position or title, and attest to 
the following:
    (1) It is your view that:
    (i) The bioengineered food is as safe as comparable food; and
    (ii) The intended use of the bioengineered food is in compliance 
with all applicable requirements of the Federal Food, Drug, and 
Cosmetic Act (the act).
    (2) You agree to make relevant data or other information that are 
not included in your PBN available to FDA upon request, either while 
FDA is evaluating your PBN or for cause.
    (3) You agree to two procedures for making relevant data or other 
information that are not included in your PBN available to FDA by:
    (i) Allowing FDA to review and copy these data or information at a 
specified address during customary business hours; or
    (ii) Sending a copy of these data or information to FDA.
    (4)(i) Your view as to whether the existence of your PBN, or any or 
all of the data or other information in your PBN, is exempt from 
disclosure under the FOIA (i.e., is confidential); and
    (ii) If you claim that the existence of the PBN, or any or all of 
the data or other information in the PBN, is confidential, you must 
explain the basis for your claim.
    (5) To the best of your knowledge, the PBN is a representative and 
balanced submission that includes information, unfavorable as well as 
favorable, pertinent to the evaluation of the safety, nutritional, or 
other regulatory issues that may be associated with the bioengineered 
food.
    (b) Part II. In your PBN, you must provide the following synopsis:
    (1) Section 1. Your name and address;
    (2) Section 2. The name of the bioengineered food that is the 
subject of the PBN and the plant species from which it is derived;
    (3) Section 3. The distinctive designation(s) that you use to 
identify the applicable transformation event(s);
    (4) Section 4. A list of the identity(ies) and source(s) of 
introduced genetic material;
    (5) Section 5. A description of the purpose or intended technical 
effect of the transformation event. This includes expected significant 
changes in the composition or characteristic properties of food derived 
from the plant as a result of the transformation event, regardless of 
whether these changes result from the insertion of new genes or from a 
modification in the expression of endogenous genes;
    (6) Section 6. A description of the applications or uses of the 
bioengineered food; and
    (7) Section 7. A description of any applications or uses that are 
not suitable for the bioengineered food.
    (c) Part III. In your PBN, you must describe the status of the 
bioengineered food at other Federal agencies and foreign governments.
    (1) Status at the U.S. Department of Agriculture, Animal and Plant 
Health Inspection Service (APHIS). A statement as to whether the 
bioengineered food plant has been the subject of an initiated or 
completed authorization, or petition for nonregulated status by APHIS, 
under 7 CFR 340.
    (2) Status at the U.S. Environmental Protection Agency (EPA). A 
statement as to whether any plant pesticide residue in the 
bioengineered food is or has been the subject of a consultation with, 
or review by, EPA and, if so, a description of the status of that 
consultation or review.
    (3) Status at foreign governments. A statement as to whether the 
bioengineered food is or has been the subject of review by any foreign 
government and, if so, a description of the status of that consultation 
or review.
    (d) Part IV. In your PBN, you must provide the following data or 
other information about the method of development of the food:
    (1) Section 1. Characterization of the parent plant including 
scientific name, taxonomic classification, mode of reproduction, and 
pertinent history of development.
    (2) Section 2. Construction of the vector used in the 
transformation of the parent plant. This includes a thorough 
characterization of the genetic material intended for introduction into 
the parent plant and a discussion of the transformation method, open 
reading frames, and regulatory sequences.

[[Page 4733]]

    (3) Section 3. Characterization of the introduced genetic material, 
including the number of insertion sites, the number of gene copies 
inserted at each site, information on deoxyribonucleic acid (DNA) 
organization within the inserts, and information on potential reading 
frames that could express unintended proteins in the transformed plant.
    (4) Section 4. Data or other information related to the inheritance 
and genetic stability of the introduced genetic material.
    (5) Section 5. A discussion, as necessary, of other relevant data 
or other information about the method of development.
    (e) Part V. In your PBN, you must discuss any newly inserted genes 
that encode resistance to an antibiotic. FDA recommends that you 
contact FDA about the agency's current thinking on this topic.
    (f) Part VI. In your PBN, you must provide the following data or 
other information about substances (other than DNA, ribonucleic acid 
(RNA), or pesticidal substances) introduced into, or modified in, the 
food (including substances that you expect to be present in the 
bioengineered food at an increased level relative to comparable food):
    (1) Section 1. Data or other information about the identity and 
function of substances introduced into, or modified in, the food;
    (2) Section 2. Data or other information relating to the level in 
the bioengineered food of substances introduced into, or modified in, 
the food;
    (3) Section 3. (i) An estimate of dietary exposure to substances 
introduced into, or modified in, the food; or
    (ii) A statement that explains the basis for your conclusion that 
an estimate of dietary exposure to these substances is not needed to 
support your view that the bioengineered food is as safe as comparable 
food.
    (4) Section 4. A discussion of the available data or other 
information that address the potential that a protein introduced into 
the food will be an allergen. FDA recommends that you contact FDA about 
the agency's current thinking on this topic.
    (5) Section 5. A discussion of data or other information relevant 
to other safety issues that may be associated with the substances 
introduced into, or modified in, the food.
    (g) Part VII. In your PBN, you must provide the following data or 
other information about the food:
    (1) Section 1. Justification for selecting a particular food(s) as 
the comparable food to which you will compare the bioengineered food.
    (2) Section 2. A discussion of historic uses of the comparable 
food(s) to which you will compare the bioengineered food.
    (3) Section 3. Data or other information comparing the composition 
and characteristics of the bioengineered food to those of comparable 
food(s), with emphasis on:
    (i) Levels of significant nutrients;
    (ii) Levels of naturally occurring toxicants and antinutrients; and
    (iii) Any intended changes to the composition of the food.
    (4) Section 4. Any other information relevant to the safety, 
nutrition, or other assessment of the bioengineered food.
    (5) Section 5. A narrative that explains the basis for your view 
that the bioengineered food is as safe as comparable food and that the 
bioengineered food is otherwise in compliance with all applicable 
requirements of the act.


Sec. 192.30  FDA evaluation and response: What will I get back from FDA 
and how long will it take?

    (a) Within 15 working days of receipt, FDA will do an initial 
evaluation of your PBN to determine whether it appears to include all 
elements required under Secs. 192.20 and 192.25.
    (1) If your PBN appears to include all required elements, the 
Center for Food Safety and Applied Nutrition (CFSAN) will file it and 
will inform the Center for Veterinary Medicine (CVM) of the filing.
    (2) If your PBN does not appear to include all required elements, 
FDA will inform you of that fact and explain what is missing.
    (b) Within 15 working days of filing a notice, FDA will send you 
(or your agent) a letter that informs you of the date on which FDA 
filed the PBN.
    (c) Within 120 days of filing a notice, FDA will send you (or your 
agent) a letter about its evaluation of your premarket notice.
    (d) In general, FDA will respond as follows:
    (1) FDA is extending its evaluation of your premarket notice by 120 
days and expects that the bioengineered food will not be marketed 
during that evaluation; or
    (2) FDA has completed its evaluation of your premarket notice. 
Based upon this evaluation, and as discussed in this letter, the 
premarket notice does not provide a basis for your view that the 
bioengineered food is as safe as comparable food or is otherwise in 
compliance with all applicable requirements of the act. Therefore, the 
agency expects that the bioengineered food will not be marketed; or
    (3) FDA has completed its evaluation of your premarket notice. 
Based upon this evaluation, the agency has no questions, at this time, 
regarding your view that the bioengineered food is as safe as 
comparable food and is otherwise in compliance with all applicable 
requirements of the act; or
    (4) FDA has received a letter in which you withdrew your PBN from 
its consideration without prejudice to a future filing. Given your 
letter, FDA ceased to evaluate your PBN on the date that we received 
your letter.
    (e) If your PBN is about a bioengineered food that contains a plant 
pesticide, FDA will describe the status of the bioengineered food at 
EPA.
    (1) If all applicable regulatory processes at EPA have come to 
closure, FDA will say so and will respond as described in paragraph (d) 
of this section.
    (2) If regulatory processes at EPA regarding the bioengineered food 
are still pending, FDA will inform you that FDA does not consider your 
PBN to satisfy the requirement for premarket notice.


Sec. 192.40  Public disclosure.

    (a) When could anyone else find out that I sent a PBN to FDA? (1) 
Ordinarily, the existence of your PBN is available for public 
disclosure on the date that FDA files it.
    (2) If you believe that the existence of your PBN is confidential, 
it is your responsibility to say so. The way to do this is by making a 
claim for confidentiality in the letter that you send in Part I of your 
PBN (Sec. 192.25(a)(4)).
    (3) If you claim that the existence of your PBN is confidential, 
FDA will evaluate your claim. FDA will disclose the existence of your 
PBN, unless FDA determines that your claim demonstrates that the 
criteria for exemption from disclosure in Sec. 20.61 of this chapter 
are satisfied.
    (4) If FDA determines that the existence of your PBN is 
confidential at the time that we file it, the existence of your PBN 
will become available for public disclosure, in accordance with 
Sec. 20.61 of this chapter, when the criteria for exemption from 
disclosure in Sec. 20.61 of this chapter are no longer satisfied.
    (b) How could anyone else find out that I sent a PBN to FDA? (1) 
FDA will make a list of filed PBN's easily accessible to the public 
(e.g., by placing the information on the Internet or in a paper or 
electronic file that is available at FDA for public review and 
copying).

[[Page 4734]]

    (2) In general, FDA will use the information submitted in Part II 
of each PBN (i.e., the information described in Sec. 192.25(b) of this 
part) to prepare this list and will update this list on an 
approximately monthly basis.
    (c) Would the data or other information in my PBN (including an 
amendment to my PBN, or any data or information that I incorporate by 
reference) be available to the public? (1) Ordinarily, the data or 
other information in your PBN are available for public disclosure, in 
accordance with Sec. 20.61 of this chapter, as of the date that FDA 
files the PBN.
    (2) If you believe that any or all of the data or other information 
in your PBN is confidential, it is your responsibility to say so. The 
way to do this is in the letter that you send in Part I of your PBN 
(Sec. 192.25(a)(4)). In addition, under Sec. 192.20(b) and (c), it is 
your responsibility to provide copies of your PBN that do not contain 
any data or other information that you claim are confidential.
    (3) If you claim that any or all of the data or other information 
in your PBN is confidential, FDA will evaluate your claim. FDA will 
disclose the data or information in your PBN unless FDA determines that 
your claim demonstrates that the criteria for exemption from disclosure 
in Sec. 20.61 of this chapter are satisfied.
    (4) If FDA determines that any or all of the data or other 
information in your PBN is confidential as of the date that we file it, 
those data or information would be available for public disclosure, in 
accordance with Sec. 20.61 of this chapter, when the criteria for 
exemption from disclosure in Sec. 20.61 of this chapter are no longer 
satisfied.
    (5) As long as the existence of your PBN is confidential, then the 
data or other information in your PBN would not be available for public 
disclosure.
    (d) How could the public obtain disclosable data and information in 
my PBN? Under the FOIA, the public could obtain the disclosable data or 
other information in your PBN or an amendment to your PBN, or that you 
incorporate by reference into your PBN, by looking for these data and 
information in FDA's electronic reading room or by asking FDA to send 
them a copy of these data and information.
    (e) Would the agency's evaluation of my PBN be available to the 
public? FDA will make the following information easily accessible to 
the public (e.g., by placing the information on the Internet or in a 
paper or electronic file that is available at FDA for public review and 
copying):
    (1) The text of any letter issued by the agency under 
Sec. 192.30(c).
    (2) The text of the agency's completed evaluation of any notice 
submitted under this part.
    2. Add part 592 to read as follows:

PART 592--PREMARKET NOTICE CONCERNING BIOENGINEERED FOOD

Sec.
592.1  Definitions: What terms do I need to know?
592.5  Requirement for premarket biotechnology notice.
592.10  Recommendation for presubmission consultation.
592.20  Premarket biotechnology notice: Administrative information.
592.25  Premarket biotechnology notice-required parts: What must I 
include in a premarket biotechnology notice?
592.30  FDA evaluation and response: What will I get back from FDA 
and how long will it take?
592.40  Public disclosure.


    Authority: 21 U.S.C. 331, 341, 343, 348, 371.


Sec. 592.1  Definitions: What terms do I need to know?

    (a) A bioengineered food means food derived from a plant that is 
developed using a transformation event.
    (b) Commercial distribution means introduction, or delivery for 
introduction, into interstate commerce for sale or exchange for 
consumption in any form by humans or other animals.
    (c) A notifier is the person who submits a premarket biotechnology 
notice under this part. Any person who is responsible for the 
development, distribution, importation, or sale of a bioengineered food 
may be a notifier.
    (d) A premarket biotechnology notice (PBN) is a submission to FDA 
regarding a bioengineered food that is intended to enter commercial 
distribution. Under this part, a PBN includes all data and information 
in the original submission and in any amendments to the original 
submission.
    (e) Transformation event means the introduction into an organism of 
genetic material that has been manipulated in vitro. For the purpose of 
this part, ``organism'' refers to plants.


Sec. 592.5  Requirement for premarket biotechnology notice.

    (a) What foods must I notify FDA about? You must notify FDA about 
any bioengineered food, including a bioengineered food derived from a 
new plant variety modified to contain a pesticidal substance, that will 
enter commercial distribution unless all of the following conditions 
are satisfied:
    (1) The bioengineered food derives from a plant line that 
represents a transformation event that has been addressed in a PBN 
previously submitted to FDA;
    (2) The use or application of the bioengineered food has been 
addressed in a notice previously submitted to FDA; and
    (3) A letter from FDA demonstrates that FDA has evaluated the use 
or application of the bioengineered food and has no questions about it. 
This would include a letter issued between May 1, 1994, and the 
effective date of this rule.
    (b) Must the data or other information that I submit to support my 
PBN be generated from a particular plant line? The data or other 
information that you submit to FDA regarding a bioengineered food must 
be generated from a plant line whose derivation can be traced to the 
transformation event that is the subject of the notice and that 
contains the genetic material introduced via the transformation event.
    (c) When do I submit my PBN? You must submit your PBN at least 120 
days before the bioengineered food is marketed.


Sec. 592.10  Recommendation for presubmission consultation.

    (a) Is there a program that provides an opportunity for me to 
consult with FDA about a bioengineered food before I submit a PBN? FDA 
has established a presubmission consultation program to enable a 
prospective notifier to identify and discuss relevant safety, 
nutritional, or other issues regarding a bioengineered food before 
submitting a PBN about that food. FDA recommends that you participate 
in this program.
    (b) How does the presubmission consultation program work? In this 
program, you inform FDA about the bioengineered food. FDA encourages 
you to discuss with us safety, nutritional, or other issues that may be 
associated with the bioengineered food. FDA will establish an 
administrative file for your consultation. Although FDA may provide 
written feedback during the consultation, that feedback would not 
release you from the requirement in Sec. 592.5 to notify FDA about the 
bioengineered food as described in Secs. 592.20 and 592.25.
    (c) Would the fact that I am consulting with FDA be confidential? 
(1) In most cases, the fact that you are consulting with FDA would not 
be confidential.
    (2) If you claim that the fact that you are consulting with FDA is 
confidential, FDA will evaluate your claim. If FDA is asked, under the 
Freedom of Information Act (FOIA), about whether you are consulting 
with us, FDA will

[[Page 4735]]

disclose that fact unless we determine that your claim demonstrates 
that the criteria for exemption from disclosure in Sec. 20.61 of this 
chapter are satisfied.
    (d) Would any of the data or other information in the 
administrative file of my consultation be disclosed to the public? (1) 
If the fact that you are consulting with FDA is not confidential, then 
the data or other information in the administrative file of your 
presubmission consultation would be available for public disclosure in 
accordance with Sec. 20.61 of this chapter.
    (2) As long as the fact that you are consulting with FDA is 
confidential, then the data or other information in the administrative 
file of your presubmission consultation would not be available for 
public disclosure.
    (e) How do I get started? To participate in the presubmission 
consultation program, write to FDA and tell us that you want to consult 
about a bioengineered food.
    (f) If I participate, what do I provide to FDA? (1) You must state 
your view as to whether the fact that you are consulting with FDA, or 
any or all of the data or other information that you submit to FDA, is 
exempt from disclosure under the FOIA (i.e., is confidential).
    (2) If you claim that the fact that you are consulting with FDA, or 
that any or all of the data or other information that you submit to 
FDA, is confidential, you must explain the basis for your claim.
    (3) We recommend that you send us the following synopsis about the 
requested consultation:
    (i) Your name and address;
    (ii) The name of the bioengineered food that is the subject of the 
presubmission consultation and the plant species from which it is 
derived;
    (iii) The distinctive designation(s) that you use to identify the 
applicable transformation event(s);
    (iv) A list of the identity(ies) and source(s) of introduced 
genetic material;
    (v) A description of the purpose or intended technical effect of 
the transformation event. This includes expected significant changes in 
the composition or characteristic properties of food derived from the 
plant as a result of the transformation event, regardless of whether 
these changes result from the insertion of new genes or from a 
modification in the expression of endogenous genes;
    (vi) A description of the intended applications or uses of the 
bioengineered food; and
    (vii) A description of any applications or uses that are not 
suitable for the bioengineered food.
    (g) Where do I send my written request for consultation? Send your 
written request for consultation about a bioengineered food to the 
Office of Premarket Approval (HFS-200), Center for Food Safety and 
Applied Nutrition, 200 C St. SW. Washington, DC 20204. As necessary and 
appropriate, the Center for Food Safety and Applied Nutrition (CFSAN) 
will coordinate FDA's evaluation of your request with the Office of 
Surveillance and Compliance, Center for Veterinary Medicine (CVM).
    (h) What copies do I send? (1) You should send an original and at 
least two paper copies of your written request for consultation.
    (2) If you submit additional written information to FDA (i.e., 
after your original written request), you should send an original and 
at least two paper copies of each additional submission.
    (3) If you claim that any specific data or other information that 
you provide to FDA during the consultation are confidential, you 
should:
    (i) Clearly identify, in each submission, the data or other 
information that you claim are confidential; and
    (ii) Prepare and submit a ``redacted'' paper copy of the submission 
(i.e., a copy that does not contain any of those data or information).
    (iii) Prepare this redacted paper copy in a manner that clearly 
identifies the location and relative size of deleted information.
    (i) What will FDA do with my written request for consultation? (1) 
FDA will establish an administrative file for your consultation and 
will place the following materials in that file:
    (i) Any correspondence between you and FDA;
    (ii) Any written materials that you provide during the consultation 
process; and
    (iii) A memorandum of each meeting or significant phone call that 
you have with FDA regarding the subject of your consultation.
    (2) If you ask FDA to discuss the bioengineered food with you, we 
will do so (e.g., at a meeting at its offices or via a telephone 
conference).


Sec. 592.20  Premarket biotechnology notice: Administrative 
information.

    (a) Where do I send my PBN? Send a PBN regarding a bioengineered 
food to the Office of Premarket Approval (HFS-200), Center for Food 
Safety and Applied Nutrition, Food and Drug Administration, 200 C St. 
SW., Washington, DC 20204. As necessary and appropriate, the Center for 
Food Safety and Applied Nutrition (CFSAN) will coordinate FDA's 
evaluation of your PBN with the Office of Surveillance and Compliance, 
Center for Veterinary Medicine (CVM).
    (b) What paper copies do I send? (1) At a minimum, you must submit 
an original paper version and one paper copy of a PBN (including any 
amendments that you make to your PBN). The original paper version will 
be the official version at FDA. If, under paragraph (c)(1) of this 
section, you choose not to send an electronic evaluation copy of your 
PBN, then you must submit one additional paper copy, for a total of 
three paper copies.
    (2) If you claim that specific data or other information in the PBN 
are confidential, you must:
    (i) Clearly identify, in each submission, the data or information 
that you claim are confidential;
    (ii) Prepare and submit a ``redacted'' paper copy of the PBN (i.e., 
a copy that does not contain any of those data or information); and
    (iii) Prepare this redacted paper copy in a manner that clearly 
identifies the location and relative size of deleted information.
    (c) What electronic copies do I send?
    (1) Evaluation copy. FDA recommends that you submit an electronic 
copy that is formatted in a manner that makes it suitable for FDA to 
use while evaluating your PBN. If you do so, you should submit such an 
electronic copy of your original PBN and of any amendments that you 
make to your PBN. To obtain current information about the technical 
format of this evaluation copy, contact the Office of Premarket 
Approval (OPA) at the address listed previously or look on OPA's home 
page on the Internet.
    (2) Disclosure copy.
    (i) Unless waived under paragraph (2)(ii) of this section, you must 
submit an electronic copy that is formatted in a manner that makes it 
suitable for FDA to use to make your PBN available to the public in an 
electronic reading room. This includes an electronic copy of your 
original PBN and of any amendments that you make to your PBN. If you 
claim that specific data or other information in the PBN are 
confidential, you must remove such data or information from the 
disclosure copy in a manner that clearly identifies the location and 
relative size of deleted information. To obtain current information 
about the technical format of this disclosure copy, write to OPA at the 
address listed previously or look on OPA's home page on the Internet.
    (ii) You may request that FDA waive the requirement for an 
electronic disclosure copy, e.g., if you do not have

[[Page 4736]]

access to the appropriate technology for formatting such a copy. FDA 
will grant or deny your request according to its merits.
    (d) May I submit any data or other information, such as a reprint 
of a published scientific article, in a foreign language? If you submit 
any material in a foreign language, you must provide an English 
translation that is verified to be complete and accurate.
    (e) May I incorporate data or other information that are already 
retained in FDA's files by referring to them? (1) If you previously 
submitted a file to FDA, you may incorporate that file by referring FDA 
to it.
    (2) If someone else previously submitted a file to FDA, the 
procedure that you may use to incorporate that file into your PBN 
depends on whether the file is publicly available (e.g., the file is in 
an electronic reading room or is otherwise available under FOIA).
    (i) If the file is publicly available, you may incorporate that 
file by referring FDA to it.
    (ii) If the file is not publicly available, you may incorporate 
that file by referring FDA to it if the person who submitted the file 
authorizes you to do so in a signed statement and you include that 
signed statement in your PBN.
    (f) How can I get additional information that will help me to 
prepare a PBN? You can obtain current guidance regarding specific 
technical issues by writing to OSC at the address listed previously or 
by looking on CVM's home page on the Internet.
    (g) May I withdraw a PBN from FDA consideration after I send it? 
(1) At any time during FDA's evaluation of a PBN, you may request that 
FDA cease to evaluate it. Your request would not preclude you from 
submitting a future PBN about the same bioengineered food.
    (2) If you request that FDA cease to evaluate your PBN, FDA will 
retain your PBN in its files and classify your PBN as ``withdrawn.''


Sec. 592.25  Premarket biotechnology notice-required parts: What must I 
include in a premarket biotechnology notice?

    A PBN has seven parts. You must include all of the information 
described in each part, or explain why it does not apply to the 
bioengineered food.
    (a) Part I. In your PBN, you must provide a letter that a 
responsible official of your organization, or your attorney or agent, 
dates and signs. In this letter, you inform FDA that you are submitting 
a PBN under Sec. 192.25 and attest to the following:
    (1) It is your view that:
    (i) The bioengineered food is as safe as comparable food; and
    (ii) The intended use of the bioengineered food is in compliance 
with all applicable requirements of the the Federal Food, Drug, and 
Cosmetic Act (the act).
    (2) You agree to make relevant data or other information that are 
not included in your PBN available to FDA upon request, either while 
FDA is evaluating your PBN or for cause.
    (3) You agree to two procedures for making relevant data or other 
information that are not included in your PBN available to FDA by:
    (i) Allowing FDA to review and copy these data or information at 
specified address during customary business hours; or
    (ii) Sending a copy of these data or information to FDA.
    (4)(i) Your view as to whether the existence of your PBN, or any or 
all of the data or other information in your PBN, is exempt from 
disclosure under the FOIA (i.e., is confidential); and
    (ii) If you claim that the existence of the PBN, or any or all of 
the data or other information in the PBN, is confidential, you must 
explain the basis for your claim.
    (5) To the best of your knowledge, the PBN is a representative and 
balanced submission that includes information, unfavorable as well as 
favorable, pertinent to the evaluation of the safety, nutritional, or 
other regulatory issues that may be associated with the bioengineered 
food.
    (b) Part II. In your PBN, you must provide the following synopsis:
    (1) Section 1. Your name and address;
    (2) Section 2. The name of the bioengineered food that is the 
subject of the PBN and the plant species from which it is derived;
    (3) Section 3. The distinctive designation(s) that you use to 
identify the applicable transformation event(s);
    (4) Section 4. A list of the identity(ies) and source(s) of 
introduced genetic material;
    (5) Section 5. A description of the purpose or intended technical 
effect of the transformation event. This includes expected significant 
changes in the composition or characteristic properties of food derived 
from the plant as a result of the transformation event, regardless of 
whether these changes result from the insertion of new genes or from a 
modification in the expression of endogenous genes;
    (6) Section 6. A description of the applications or uses of the 
bioengineered food; and
    (7) Section 7. A description of any applications or uses that are 
not suitable for the bioengineered food.
    (c) Part III. In your PBN, you must describe the status of the 
bioengineered food at other Federal agencies and foreign governments.
    (1) Status at the U.S. Department of Agriculture, Animal and Plant 
Health Inspection Service (APHIS). A statement as to whether the 
bioengineered food plant has been the subject of an initiated or 
completed authorization, or petition for nonregulated status by APHIS, 
under 7 CFR part 340.
    (2) Status at the U.S. Environmental Protection Agency (EPA). A 
statement as to whether any plant pesticide residue in the 
bioengineered food is or has been the subject of a consultation with, 
or review by, EPA and, if so, a description of the status of that 
consultation or review.
    (3) Status at foreign governments. A statement as to whether the 
bioengineered food is or has been the subject of review by any foreign 
government and, if so, a description of the status of that consultation 
or review.
    (d) Part IV. In your PBN, you must provide the following data or 
other information about the method of development of the food:
    (1) Section 1. Characterization of the parent plant including 
scientific name, taxonomic classification, mode of reproduction, and 
pertinent history of development.
    (2) Section 2. Construction of the vector used in the 
transformation of the parent plant. This includes a thorough 
characterization of the genetic material intended for introduction into 
the parent plant and a discussion of the transformation method, open 
reading frames, and regulatory sequences.
    (3) Section 3. Characterization of the introduced genetic material, 
including the number of insertion sites, the number of gene copies 
inserted at each site, information on deoxyribonucleic acide (DNA) 
organization within the inserts, and information on potential reading 
frames that could express unintended proteins in the transformed plant.
    (4) Section 4. Data or other information related to the inheritance 
and genetic stability of the introduced genetic material.
    (5) Section 5. A discussion, as necessary, of other relevant data 
or other information about the method of development.
    (e) Part V. In your PBN, you must discuss any newly inserted genes 
that encode resistance to an antibiotic. FDA recommends that you 
contact FDA about the agency's current thinking on this topic.
    (f) Part VI. In your PBN, you must provide the following data or 
other information about substances (other than DNA, ribonucleic acid 
(RNA), or

[[Page 4737]]

pesticidal substances) introduced into, or modified in, the food 
(including substances that you expect to be present in the 
bioengineered food at an increased level relative to comparable food):
    (1) Section 1. Data or other information about the identity and 
function of substances introduced into, or modified in, the food;
    (2) Section 2. Data or other information relating to the level in 
the bioengineered food of substances introduced into, or modified in, 
the food;
    (3) Section 3. (i) An estimate of dietary exposure to substances 
introduced into, or modified in, the food; or
    (ii) A statement that explains the basis for your conclusion that 
an estimate of dietary exposure to these substances is not needed to 
support your view that the bioengineered food is as safe as comparable 
food.
    (4) Section 4. A discussion of the available data or other 
information that address the potential that a protein introduced into 
the food will be an allergen. FDA recommends that you contact FDA about 
the agency's current thinking on this topic.
    (5) Section 5. A discussion of data or other information relevant 
to other safety issues that may be associated with the substances 
introduced into, or modified in, the food.
    (g) Part VII. In your PBN, you must provide the following data or 
other information about the food:
    (1) Section 1. Justification for selecting a particular food(s) as 
the comparable food to which you will compare the bioengineered food.
    (2) Section 2. A discussion of historic uses of the comparable 
food(s) to which you will compare the bioengineered food.
    (3) Section 3. Data or other information comparing the composition 
and characteristics of the bioengineered food to those of comparable 
food(s), with emphasis on:
    (i) Levels of significant nutrients;
    (ii) Levels of naturally occurring toxicants and antinutrients; and
    (iii) Any intended changes to the composition of the food.
    (4) Section 4. Any other information relevant to the safety, 
nutrition, or other assessment of the bioengineered food.
    (5) Section 5. A narrative that explains the basis for your view 
that the bioengineered food is as safe as comparable food and that the 
bioengineered food is otherwise in compliance with all applicable 
requirements of the act.


Sec. 592.30  FDA evaluation and response: What will I get back from FDA 
and how long will it take?

    (a) Within 15 working days of receipt, FDA will do an initial 
evaluation of your PBN to determine whether it appears to include all 
elements required under Secs. 592.20 and 592.25.
    (1) If your PBN appears to include all required elements, the 
Center for Food Safety and Applied Nutrition (CFSAN) will file it and 
will inform the Center for Veterinary Medicine (CVM) of the filing.
    (2) If your PBN does not appear to include all required elements, 
FDA will inform you of that fact and explain what is missing.
    (b) Within 15 working days of filing a notice, FDA will send you 
(or your agent) a letter that informs you of the date on which FDA 
filed the PBN.
    (c) Within 120 days of filing a notice, FDA will send you (or your 
agent) a letter about its evaluation of your premarket notice.
    (d) In general, FDA will respond as follows:
    (1) FDA is extending its evaluation of your premarket notice by 120 
days and expects that the bioengineered food will not be marketed 
during that evaluation; or
    (2) FDA has completed its evaluation of your premarket notice. 
Based upon this evaluation, and as discussed in this letter, the 
premarket notice does not provide a basis for your view that the 
bioengineered food is as safe as comparable food or is otherwise in 
compliance with all applicable requirements of the act. Therefore, the 
agency expects that the bioengineered food will not be marketed; or
    (3) FDA has completed its evaluation of your premarket notice. 
Based upon this evaluation, the agency has no questions, at this time, 
regarding your view that the bioengineered food is as safe as 
comparable food and is otherwise in compliance with all applicable 
requirements of the act; or
    (4) FDA has received a letter in which you withdrew your PBN from 
its consideration without prejudice to a future filing. Given your 
letter, FDA ceased to evaluate your PBN on the date that we received 
your letter.
    (e) If your PBN is about a bioengineered food that contains a plant 
pesticide, FDA will describe the status of the bioengineered food at 
EPA.
    (1) If all applicable regulatory processes at EPA have come to 
closure, FDA will say so and will respond as described in paragraph (d) 
of this section.
    (2) If regulatory processes at EPA regarding the bioengineered food 
are still pending, FDA will inform you that FDA does not consider your 
PBN to satisfy the requirement for premarket notice.


Sec. 592.40  Public disclosure.

    (a) When could anyone else find out that I sent a PBN to FDA? (1) 
Ordinarily, the existence of your PBN is available for public 
disclosure on the date that FDA files it.
    (2) If you believe that the existence of your PBN is confidential, 
it is your responsibility to say so. The way to do this is by making a 
claim for confidentiality in the letter that you send in Part I of your 
PBN (Sec. 592.25(a)(4)).
    (3) If you claim that the existence of your PBN is confidential, 
FDA will evaluate your claim. FDA will disclose the existence of your 
PBN, unless FDA determines that your claim demonstrates that the 
criteria for exemption from disclosure in Sec. 20.61 of this chapter 
are satisfied.
    (4) If FDA determines that the existence of your PBN is 
confidential at the time that we file it, the existence of your PBN 
will become available for public disclosure, in accordance with 
Sec. 20.61 of this chapter, when the criteria for exemption from 
disclosure in Sec. 20.61 of this chapter are no longer satisfied.
    (b) How could anyone else find out that I sent a PBN to FDA?
    (1) FDA will make a list of filed PBN's easily accessible to the 
public (e.g., by placing the information on the Internet or in a paper 
or electronic file that is available at FDA for public review and 
copying).
    (2) In general, FDA will use the information submitted in Part II 
of each PBN (i.e., the information described in Sec. 192.25(b) of this 
chapter) to prepare this list and will update this list on an 
approximately monthly basis.
    (c) Would the data or other information in my PBN (including an 
amendment to my PBN, or any data or information that I incorporate by 
reference) be available to the public? (1) Ordinarily, the data or 
other information in your PBN are available for public disclosure, in 
accordance with Sec. 20.61 of this chapter, as of the date that FDA 
files the PBN.
    (2) If you believe that any or all of the data or other information 
in your PBN is confidential, it is your responsibility to say so. The 
way to do this is in the letter that you send in Part I of your PBN 
(Sec. 592.25(a)(4)). In addition, under Sec. 592.20(b) and (c), it is 
your responsibility to provide copies of your PBN that do not contain 
any data or other information that you claim are confidential.

[[Page 4738]]

    (3) If you claim that any or all of the data or other information 
in your PBN is confidential, FDA will evaluate your claim. FDA will 
disclose the data or information in your PBN, unless FDA determines 
that your claim demonstrates that the criteria for exemption from 
disclosure in Sec. 20.61 of this chapter are satisfied.
    (4) If FDA determines that any or all of the data or other 
information in your PBN is confidential as of the date that we file it, 
those data or information would be available for public disclosure, in 
accordance with 20.61 of this chapter, when the criteria for exemption 
from disclosure in Sec. 20.61 of this chapter are no longer satisfied.
    (5) As long as the existence of your PBN is confidential, then the 
data or other information in your PBN would not be available for public 
disclosure.
    (d) How could the public obtain disclosable data and information in 
my PBN? Under the FOIA, the public could obtain the disclosable data or 
other information in your PBN or an amendment to your PBN, or that you 
incorporate by reference into your PBN, by looking for these data and 
information in FDA's electronic reading room or by asking FDA to send 
them a copy of these data and information.
    (e) Would the agency's evaluation of my PBN be available to the 
public?
    FDA will make the following information easily accessible to the 
public (e.g., by placing the information on the Internet or in a paper 
or electronic file that is available at FDA for public review and 
copying):
    (1) The text of any letter issued by the agency under 
Sec. 192.30(c) of this chapter.
    (2) The text of the agency's completed evaluation of any notice 
submitted under this part.

    Dated: September 22, 2000.
Jane E. Henney,
Commissioner of Food and Drugs.
Donna E. Shalala,
Secretary of Health and Human Services.
[FR Doc. 01-1046 Filed 1-17-01; 8:45 am]
BILLING CODE 4160-01-F