4706 Federal Register / Vol. 66, No. 12 / Thursday, January 18, 2001 / Proposed Rules

withdrawn, the dates of these actions,

and the reasons for these actions.

(10) Other relevant data and

information that the Director, CBER,

determines are necessary for the

appropriate consideration of the public

health and scientific issues, including

relevant ethical issues, raised by human

gene therapy or xenotransplantation.

10. Section 601.53 is added to subpart

F to read as follows:

§ 601.53 Submission of certain data and

information related to human gene therapy

or xenotransplantation for public

disclosure.

(a) A sponsor of an IND shall submit

to FDA for public disclosure in a

redacted version the submissions

identified in paragraphs (b)(1) through

(b)(5) of this section. Each submission

shall include all applicable information

identified as disclosable in § 601.52, but

shall be redacted to remove or obscure

all information considered confidential

as a trade secret, certain confidential

commercial information, such as

information regarding commercial

licensing agreements or the

identification of suppliers, and names

and other personal identifiers of

patients and, except as specifically

provided in this section, names and

personal identifiers of any third party,

such as physicians or hospitals, must be

redacted.

(b) The following shall be submitted

in a suitably redacted version and in

duplicate at the time points noted:

(1) Information as defined under

§ 601.52 at the time of initial IND

submission.

(2) Any amendment documenting

changes or additions to the information

as defined under § 601.52 at the time the

amendment goes into effect.

(3) IND safety reports at the time of

submission of the initial report to FDA.

(4) The annual report, within 60 days

of the anniversary date that the IND

went into effect, in accordance with

§ 312.33 of this chapter.

(5) Other information upon the

specific request of the Director, CBER.

(c) The submissions identified in

paragraph (b) of this section shall be

submitted in a form readily separable

from the original unabridged

submission to FDA and clearly marked

on each page of the redacted version as

suitable for public disclosure.

(d) Any copies of copyrighted

material shall be submitted in a single

appendix to each redacted version.

Copyrighted materials whose copyright

is not owned by the applicant shall not

be included in any other section of the

redacted versions. A bibliography of

copyrighted materials contained in the

appendix shall be included as part of

each redacted version.

(e) Any data or information submitted

to FDA as a redacted version for public

disclosure in accordance with paragraph

(a) of this section shall be accompanied

by the following statement signed by a

responsible individual:

The information contained herein has

been redacted for public disclosure. The

only material removed from these

records is: Confidential commercial or

trade secret information exempt from

disclosure under the Freedom of

Information Act (5 U.S.C. 552 (b)(4)) and

the Food and Drug Administration’s

implementing regulations (21 CFR

20.61); names and other personal

identifiers of patients and, except as

specifically provided in the regulations,

names and other personal identifiers of

any third party.

I declare, under the penalty of perjury, that

the foregoing is true and correct.

Dated: December 20, 2000.

Jane E. Henney,

Commissioner of Food and Drugs.

Donna E. Shalala,

Secretary of Health and Human Services.

[FR Doc. 01–1048 Filed 1–17–01; 8:45 am]

BILLING CODE 4160–01–F

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 plantderived 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

Federal Register / Vol. 66, No. 12 / Thursday, January 18, 2001 / Proposed Rules 4707

1This 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.

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 § 192.20(a) through (b)(1) and

§ 192.25

B. Hourly Reporting Burden Associated

With Confidential Information in a

Report (Proposed § 192.20(b)(2)(i) and

(b)(2)(ii)

C. Hourly Reporting Burden Associated

With Electronic Copies of the Report

(Proposed § 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

§ 192.20(d), (e), and (g)

E. Hourly Reporting Burden Associated

With a Voluntary Presubmission

Consultation Program (Proposed

§ 192.10(e) through (g), (h)(2), (h)(3)(i),

and (h)(3)(ii)

F. Hourly Recordkeeping Burden

(Proposed § 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

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

4708 Federal Register / Vol. 66, No. 12 / Thursday, January 18, 2001 / Proposed Rules

2This consultation was concluded in May 1994

(59 FR 26647 at 26700, May 23, 1994).

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).

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.

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. 6There are certain exceptions to this jurisdiction

pertaining to meat, poultry, and egg products that

are not relevant to this rulemaking.

consultation involved FLAVR SAVRTM

tomatoes.2 In developing FLAVR SAVTM

tomatoes, Calgene used rDNA

technology to introduce an antisense

polygalacturonase gene, which was

derived from tomatoes, and the

kanamycin resistance gene (the kan r

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.

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.

In contrast, issues raised during the

consultations on APH(3′)II and the

FLAVR SAVRTM 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 SAVRTM tomatoes, ‘‘Northern

blots’’ to demonstrate the intended

technical effect in FLAVR SAVRTM

tomatoes, and ‘‘Western blots’’ to

determine the amount of APH(3′)II

present in FLAVR SAVRTM 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.

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

§ 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).

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

Federal Register / Vol. 66, No. 12 / Thursday, January 18, 2001 / Proposed Rules 4709

7The 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.

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).

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, wellcharacterized 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 plantderived 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.

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

4710 Federal Register / Vol. 66, No. 12 / Thursday, January 18, 2001 / Proposed Rules

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

Federal Register / Vol. 66, No. 12 / Thursday, January 18, 2001 / Proposed Rules 4711

8For 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.

9These include modifications for altered protein

quality, increased carotenoid content, increased

fruit solids, altered fiber quality, and increased fruit

sweetness, among others.

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 wellestablished 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

4712 Federal Register / Vol. 66, No. 12 / Thursday, January 18, 2001 / Proposed Rules

to be utilized by plant breeders to an

increasingly greater extent.

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 § 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 § 192.5). The

proposed regulation would include a

bioengineered food derived from a new

Federal Register / Vol. 66, No. 12 / Thursday, January 18, 2001 / Proposed Rules 4713

10The 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.

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 § 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

§ 192.5(a)(1)). Under § 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

§ 192.5(a)(2)). Under § 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

§ 192.5(a)(3)). Under § 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

§ 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 § 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

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

4714 Federal Register / Vol. 66, No. 12 / Thursday, January 18, 2001 / Proposed Rules

(proposed § 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

§ 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 § 192.10(a)). Under the

program (proposed § 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 § 192.10(c)) and (2) the data

or information in the file that FDA

would establish for a presubmission

consultation (proposed § 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 § 20.61 (21 CFR 20.61)

(proposed § 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

§ 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 § 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

§ 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 § 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

§ 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

Federal Register / Vol. 66, No. 12 / Thursday, January 18, 2001 / Proposed Rules 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 § 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 § 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

§ 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

§ 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 § 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 § 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 § 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

4716 Federal Register / Vol. 66, No. 12 / Thursday, January 18, 2001 / Proposed Rules

11Under 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.

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 § 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 (§ 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 § 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 § 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

§ 192.20(c)(1) and section VII.C of this

document).

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

§ 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 § 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 § 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

Federal Register / Vol. 66, No. 12 / Thursday, January 18, 2001 / Proposed Rules 4717

12FDA 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.

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 § 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., § 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 § 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 (§ 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

§ 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 § 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 (§ 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

§ 192.25). These would include a letter

(proposed § 192.25(a)); a synopsis

(proposed § 192.25(b)); administrative

statements about the status of review of

the bioengineered food by other Federal

agencies or by foreign governments

(proposed § 192.25(c)); data or

information about the method of

development (proposed § 192.25(d)); a

discussion of any newly inserted genes

that encode resistance to an antibiotic

(proposed § 192.25(e)); data or

information about substances

introduced into, or modified in, the food

(proposed § 192.25(f)); and data or

information about the food (proposed

§ 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

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 § 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

4718 Federal Register / Vol. 66, No. 12 / Thursday, January 18, 2001 / Proposed Rules

13Under 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.

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 § 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

§ 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 § 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 § 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 § 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 § 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

§ 192.25(b)) that includes the same

information that FDA is recommending

for inclusion in a presubmission

consultation (see proposed § 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 § 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

§ 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 § 192.30(e) and section IX.C.5

of this document).

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

§ 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

Federal Register / Vol. 66, No. 12 / Thursday, January 18, 2001 / Proposed Rules 4719

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 kanr 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.

15A report that describes the consultations that

FDA relied on in developing this draft guidance is

available (Ref. 16).

16As 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).

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 § 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 § 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

§ 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

§ 192.25(d)(3)); and (4) data or

information related to the inheritance

and genetic stability of the introduced

genetic material (proposed

§ 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 § 192.25(d)(5)).

This requirement would cover any

issues about the method of development

that are not explicitly addressed in

proposed § 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 § 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.

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 § 192.25(f)). These data or

information would include data or

information about the identity and

function of these substances (proposed

§ 192.25(f)(1)), the level of these

substances in the bioengineered food

(proposed § 192.25(f)(2)), dietary

exposure to these substances (proposed

§ 192.25(f)(3)), the potential that a

protein introduced into the food will be

an allergen (proposed § 192.25(f)(4)),

and a discussion of other safety issues

that may be associated with these

substances (proposed § 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 § 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.

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

§ 192.25(f)(1)) and the level in the

bioengineered food of these substances

(proposed § 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

4720 Federal Register / Vol. 66, No. 12 / Thursday, January 18, 2001 / Proposed Rules

17The 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.

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

§ 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

§ 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

§ 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

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 § 192.25(f)(5)). This

requirement would cover any issues that

are not explicitly addressed in proposed

§ 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

§ 192.25(g)). These data or information

would include a justification for

selecting a particular food(s) as

‘‘comparable food’’ (proposed

§ 192.25(g)(1)); a discussion of historic

uses of the comparable food(s)

(proposed § 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 § 192.25(g)(3)); any other

information relevant to the safety,

nutritional, or other regulatory

assessment of the bioengineered food

(proposed § 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

§ 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 § 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 § 192.25(g)(2)). Several

Federal Register / Vol. 66, No. 12 / Thursday, January 18, 2001 / Proposed Rules 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 § 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 § 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 B12 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 § 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

§ 192.25(g)(4)). This requirement would

cover any legal status issues about the

food that are not explicitly addressed in

proposed § 192.25(g)(1), (g)(2), and

(g)(3). For example, under proposed

§ 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 technicallyproficient 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

§ 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 §§ 192.20 and 192.25 (proposed

§ 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

§ 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 (§ 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

4722 Federal Register / Vol. 66, No. 12 / Thursday, January 18, 2001 / Proposed Rules

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 § 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 § 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 § 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

§ 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

§ 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 § 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 § 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

§ 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 § 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,

Federal Register / Vol. 66, No. 12 / Thursday, January 18, 2001 / Proposed Rules 4723

18Section 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.

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 § 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 § 192.30(e)). If all

applicable regulatory processes at EPA

have come to closure (proposed

§ 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

§ 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 § 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 § 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 § 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

§ 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

§ 20.61 are satisfied (proposed

§ 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 § 20.61, when the

criteria for exemption from disclosure

are no longer satisfied (proposed

§ 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 § 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

§ 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

§ 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 § 20.61 are satisfied

(proposed § 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 § 20.61, when the

criteria for exemption from disclosure

are no longer satisfied (proposed

§ 192.40(c)(4)).18

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 § 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 § 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 § 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.

4724 Federal Register / Vol. 66, No. 12 / Thursday, January 18, 2001 / Proposed Rules

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

§ 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

Federal Register / Vol. 66, No. 12 / Thursday, January 18, 2001 / Proposed Rules 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

21 CFR Section No. of

Respondents

Annual

Frequency per

Response

Total Annual ResponsesHours per

Response Total 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 192.25 20 1 20 190 3,800

Total 4,417.50

1There are no capital costs or operating and maintenance costs associated with this collection of information.

TABLE 2.—ESTIMATED ANNUAL RECORDKEEPING BURDEN 1

21 CFR Section No. of

Recordkeepers

Annual

Frequency per Recordkeeping

Total Annual

Records

Hours per

Recordkeeper Total Hours

192.25(a)(2) 20 1 20 19 380

Total 380

1There 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

4726 Federal Register / Vol. 66, No. 12 / Thursday, January 18, 2001 / Proposed Rules

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 §§ 192.20(a) through (b)(1)

and § 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 § 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 §§ 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 § 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).

Federal Register / Vol. 66, No. 12 / Thursday, January 18, 2001 / Proposed Rules 4727

E. Hourly Reporting Burden Associated

With a Voluntary Presubmission

Consultation Program (Proposed

§ 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 § 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

4728 Federal Register / Vol. 66, No. 12 / Thursday, January 18, 2001 / Proposed Rules

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.

Federal Register / Vol. 66, No. 12 / Thursday, January 18, 2001 / Proposed Rules 4729

TABLE 3.

Number of submissions per yearTime costs per submission (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.

4730 Federal Register / Vol. 66, No. 12 / Thursday, January 18, 2001 / Proposed Rules

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

§ 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.

§ 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.

§ 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.

Federal Register / Vol. 66, No. 12 / Thursday, January 18, 2001 / Proposed Rules 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

§ 192.5 to notify FDA about the

bioengineered food as described in

§§ 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

§ 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 § 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).

§ 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)

4732 Federal Register / Vol. 66, No. 12 / Thursday, January 18, 2001 / Proposed Rules

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.’’

§ 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 § 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.

Federal Register / Vol. 66, No. 12 / Thursday, January 18, 2001 / Proposed Rules 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.

§ 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 §§ 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.

§ 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

(§ 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 § 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

§ 20.61 of this chapter, when the criteria

for exemption from disclosure in § 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).

4734 Federal Register / Vol. 66, No. 12 / Thursday, January 18, 2001 / Proposed Rules

(2) In general, FDA will use the

information submitted in Part II of each

PBN (i.e., the information described in

§ 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 § 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 (§ 192.25(a)(4)). In addition, under

§ 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 § 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 § 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 § 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.

§ 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.

§ 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.

§ 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

§ 592.5 to notify FDA about the

bioengineered food as described in

§§ 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

Federal Register / Vol. 66, No. 12 / Thursday, January 18, 2001 / Proposed Rules 4735

disclose that fact unless we determine

that your claim demonstrates that the

criteria for exemption from disclosure in

§ 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 § 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).

§ 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

4736 Federal Register / Vol. 66, No. 12 / Thursday, January 18, 2001 / Proposed Rules

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.’’

§ 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 § 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

Federal Register / Vol. 66, No. 12 / Thursday, January 18, 2001 / Proposed Rules 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.

§ 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 §§ 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.

§ 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

(§ 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 § 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

§ 20.61 of this chapter, when the criteria

for exemption from disclosure in § 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

§ 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 § 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 (§ 592.25(a)(4)). In addition, under

§ 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.

4738 Federal Register / Vol. 66, No. 12 / Thursday, January 18, 2001 / Proposed Rules

(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 § 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 § 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 § 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

DEPARTMENT OF THE TREASURY

Internal Revenue Service

26 CFR Part 1

[REG–107047–00]

RIN 1545–AY02

Hedging Transactions

AGENCY: Internal Revenue Service (IRS),

Treasury.

ACTION: Notice of proposed rulemaking

and notice of public hearing.

SUMMARY: This document contains

proposed regulations relating to the

character of hedging transactions. These

proposed regulations reflect changes to

the law made by the Ticket to Work and

Work Incentives Improvement Act of

1999. The proposed regulations affect

businesses entering into hedging

transactions. This document also

provides notice of a public hearing on

these proposed regulations.

DATES: Written or electronically

generated comments must be received

by April 25, 2001. Requests to speak

(with outlines of oral comments to be

discussed) at the public hearing

scheduled for May 16, 2001, at 10 a.m.,

must be submitted by April 25, 2001.

ADDRESSES: Send submissions to:

CC:M&SP:RU (REG–107047–00), room

5226, Internal Revenue Service, POB

7604, Ben Franklin Station, Washington,

DC 20044. Submissions may be hand

delivered between the hours of 8 a.m.

and 5 p.m. to: CC:M&SP:RU (REG–

107047–00), Courier’s Desk, Internal

Revenue Service, 1111 Constitution

Avenue NW., Washington, DC.

Alternatively, taxpayers may submit

comments electronically via the Internet

by selecting the ‘‘Tax Regs’’ option on

the IRS Home Page, or by submitting

comments directly to the IRS internet

site at http://www.irs.gov/taxlregs/

regslist.html. The public hearing will be

held in the IRS auditorium, 1111

Constitution Ave., NW., Washington,

DC.

FOR FURTHER INFORMATION CONTACT:

Concerning the regulations, Jo Lynn

Ricks, (202) 622–3920; concerning

submissions of comments, the hearing,

and/or to be placed on the building

access list to attend the hearing, contact

Lanita Vandyke, (202) 622–7180 (not

toll-free numbers).

SUPPLEMENTARY INFORMATION:

Paperwork Reduction Act

The collection of information

contained in this notice of proposed

rulemaking has been reviewed and

approved by the Office of Management

and Budget in accordance with the

Paperwork Reduction Act of 1995 (44

U.S.C. 3507(d)) under control numbers

1545–1403 and 1545–1480.

An agency may not conduct or

sponsor, and a person is not required to

respond to, a collection of information

unless it displays a valid control

number assigned by the Office of

Management and Budget.

Books or records relating to a

collection of information must be

retained as long as their contents may

become material in the administration

of any internal revenue law. Generally,

tax returns and tax return information

are confidential, as required by 26

U.S.C. 6103.

Background

This document contains proposed

amendments to 26 CFR part 1 under

section 1221 of the Internal Revenue

Code (Code). Prior to amendment in

1999, section 1221 generally defined a

capital asset as property held by the

taxpayer other than: (1) Stock in trade

or other types of assets includible in

inventory; (2) property used in a trade

or business that is real property or

property subject to depreciation; (3)

certain copyrights (or similar property);

(4) accounts or notes receivable

acquired in the ordinary course of a

trade or business; and (5) U.S.

government publications.

In 1994, the IRS published in the

Federal Register (59 FR 36360) final

Treasury regulations under section 1221

providing for ordinary character

treatment for most business hedges. The

regulations generally apply to hedges

that reduce risk with respect to ordinary

property, ordinary obligations, and

borrowings of the taxpayer and that

meet certain identification

requirements. (§ 1.1221–2). In 1996, the

IRS published in the Federal Register

(61 FR 517) final regulations on the

character and timing of gain or loss from

hedging transactions entered into by

members of a consolidated group. The

final regulations published in 1994 and

1996 are collectively referred to as the

Treasury regulations in this preamble.

On December 17, 1999, section 1221

was amended by section 532 of the

Ticket to Work and Work Incentives

Improvement Act of 1999 (113 Stat.

1860) to provide ordinary gain or loss

treatment for hedging transactions and

consumable supplies. Section 1221(a)(7)

provides ordinary treatment for hedging

transactions that are clearly identified as

such before the close of the day on

which they were acquired, originated, or

entered into.

The statute defines a hedging

transaction generally to include a

transaction entered into by the taxpayer

in the normal course of business

primarily to manage risk of interest rate,

price changes, or currency fluctuations

with respect to ordinary property,

ordinary obligations, or borrowings of

the taxpayer. § 1221(b)(2)(A)(i) and (ii).

The statutory definition of hedging

transaction also includes transactions to

manage such other risks as the Secretary

may prescribe in regulations. Section

1221(b)(2)(A)(iii). Further, the statute