Federal Register / Vol. 69, No. 226 / Wednesday, November 24, 2004 / Notices 68381

1 Guidance on Consultation Procedures: Foods 

Derived from New Plant Varieties can be found at 

http://www.cfsan.fda.gov/~lrd/consulpr.html.

B. Final Consultations

Final consultations are a one-time 

burden. At some stage in the process of 

research and development, a developer 

will have accumulated the information 

that the developer believes is adequate 

to ensure that food derived from the 

new plant variety is safe and that it 

demonstrates compliance with the 

relevant provisions of the act. The 

developer will then be in a position to 

conclude any ongoing consultation with 

FDA. The developer submits to FDA a 

summary of the safety and nutritional 

assessment that has been conducted 

about the bioengineered food that is 

intended to be introduced into 

commercial distribution. FDA evaluates 

the submission to ensure that all 

potential safety and regulatory questions 

have been addressed.

Summary information of the safety 

and nutritional assessment for a new 

plant variety submitted to FDA includes 

the following information:

•The name of the bioengineered food 

and the crop from which it is derived;

• A description of the various 

applications or uses of the 

bioengineered food, including animal 

feed uses;

• Information concerning the sources, 

identities, and functions of introduced 

genetic material;

• Information on the purpose or 

intended technical effect of the 

modification, and its expected effect on 

the composition or characteristic 

properties of the food or feed;

• Information concerning the identity 

and function of expression products 

encoded by the introduced genetic 

material, including an estimate of the 

concentration of any expression product 

in the bioengineered crop or food 

derived therefrom;

• Information regarding any known or 

suspected allergenicity and toxicity of 

expression products and the basis for 

concluding that foods containing the 

expression products can be safely 

consumed;

• Information comparing the 

composition or characteristics of the 

bioengineered food to that of food 

derived from the parental variety or 

other commonly consumed varieties of 

the same crop with special emphasis on 

important nutrients, and toxicants that 

occur naturally in the food;

• A discussion of the available 

information that addresses whether the 

potential for the food derived from a 

bioengineered plant to induce an 

allergic response has been altered by the 

genetic modification; and

• Any other information relevant to 

the safety and nutritional assessment of 

the bioengineered food.

In 2001 FDA contacted five firms that 

had made one or more biotechnology 

consultation submissions under the 

1996 procedures. FDA asked each of 

these firms for an estimate of the hourly 

burden to prepare a submission under 

the voluntary biotechnology 

consultation 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 for 

final consultation under the 1996 

procedures is 150 hours.

Dated: November 12, 2004.

Jeffrey Shuren,

Assistant Commissioner for Policy.

[FR Doc. 04–26048 Filed 11–19–04; 1:52 pm]

BILLING CODE 4160–01–S

DEPARTMENT OF HEALTH AND 

HUMAN SERVICES

Food and Drug Administration

[Docket No. 2004D–0369]

Draft Guidance for Industry: 

Recommendations for the Early Food 

Safety Evaluation of New NonPesticidal Proteins Produced by New 

Plant Varieties Intended for Food Use; 

Availability

AGENCY: Food and Drug Administration, 

HHS.

ACTION: Notice.

SUMMARY: The Food and Drug 

Administration (FDA) is announcing the 

availability of a draft guidance for 

industry entitled ‘‘Recommendations for 

the Early Food Safety Evaluation of New 

Non-Pesticidal Proteins Produced by 

New Plant Varieties Intended for Food 

Use.’’ The draft guidance, when 

finalized, is intended to provide 

recommendations to developers of new 

plant varieties, in particular 

bioengineered plants, on the early food 

safety evaluation of new non-pesticidal 

proteins. The draft guidance describes 

procedures for submitting an early food 

safety evaluation of such proteins to the 

agency.

DATES: Submit written or electronic 

comments concerning the draft 

guidance and the collection of 

information provisions by January 24, 

2005.

ADDRESSES: Submit written requests for 

single copies of the draft guidance 

entitled ‘‘Recommendations for the 

Early Food Safety Evaluation of New 

Non-Pesticidal Proteins Produced by 

New Plant Varieties Intended for Food 

Use’’ to Mary D. Ditto, Center for Food 

Safety and Applied Nutrition (HFS–

255), Food and Drug Administration, 

5100 Paint Branch Pkwy., College Park, 

MD 20740, 301–436–1165. Send one 

self-adhesive address label to assist that 

office in processing your request, or 

include a fax number to which the draft 

guidance may be sent. See the 

SUPPLEMENTARY INFORMATION section for 

electronic access to the draft guidance.

Submit written comments concerning 

the draft guidance and the collection of 

information provisions to the Division 

of Dockets Management (HFA–305), 

Food and Drug Administration, 5630 

Fishers Lane, rm. 1061, Rockville, MD 

20852. Submit electronic comments to 

http://www.fda.gov/dockets/ecomments.

FOR FURTHER INFORMATION CONTACT:

Mary D. Ditto, Center for Food Safety 

and Applied Nutrition (HFS–255), Food 

and Drug Administration, 5100 Paint 

Branch Pkwy., College Park, MD 20740, 

301–436–1165, FAX 301–436–2965, email: mditto@cfsan.fda.gov.

SUPPLEMENTARY INFORMATION:

I. Background

In a document in the Federal Register

of August 2, 2002 (67 FR 50578), the 

U.S. Office of Science and Technology 

Policy (OSTP) proposed Federal actions 

to update field test requirements and to 

establish early voluntary food safety 

evaluations for new proteins produced 

by bioengineered plants. Rapid 

developments in genomics are resulting 

in dramatic changes in the way new 

plant varieties are developed and 

commercialized. Scientific advances are 

expected to accelerate over the next 

decade, leading to the development and 

commercialization of a greater number 

and diversity of bioengineered crops. As 

the number and diversity of field tests 

for bioengineered plants increase, the 

likelihood that cross-pollination due to 

pollen drift from field tests to 

commercial fields and commingling of 

seeds produced during field tests with 

commercial seeds or grain may also 

increase. This could result in the 

inadvertent, intermittent, low-level 

presence in the food supply of proteins 

that have not been evaluated through 

FDA’s voluntary consultation 

procedures for foods derived from new 

plant varieties (referred to as 

‘‘biotechnology consultation’’ in the 

case of bioengineered plants).1 FDA is 

issuing a draft guidance document to 

address this possibility.

This draft guidance describes the 

procedure for early food safety 

evaluation of new proteins produced by 

new plant varieties that are under

68382 Federal Register / Vol. 69, No. 226 / Wednesday, November 24, 2004 / Notices 

development. While this guidance is 

focused on new proteins in 

bioengineered plants, these procedures 

may, of course, be used for new proteins 

in non-bioengineered foods as well. 

This draft guidance also provides 

information to sponsors and developers 

about submitting their evaluation to 

FDA.

This level 1 draft guidance is being 

issued consistent with FDA’s good 

guidance practices regulations (21 CFR 

10.115). The draft guidance, when 

finalized, will represent FDA’s current 

thinking on the early food safety 

assessment of new proteins produced by 

new plant varieties intended for food 

use. It does not create or confer any 

rights, for or on any person, and does 

not operate to bind FDA or the public. 

You can use an alternative approach if 

the approach satisfies the requirements 

of the applicable statutes and 

regulations. If you want to discuss an 

alternative approach, contact the FDA 

staff responsible for implementing the 

guidance. If you cannot identify the 

appropriate FDA staff, call the 

telephone number listed in the title page 

of the guidance.

II. Paperwork Reduction Act of 1995

This draft guidance document 

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). Under the PRA, Federal agencies 

must obtain approval from the OMB for 

each collection of information they 

conduct or sponsor. ‘‘Collection of 

information’’ is defined in 44 U.S.C. 

3502(3) and 5 CFR 1320.3 and includes 

agency requests or requirements that 

members of the public submit reports, 

keep records, or provide information to 

a third party. Section 3506(c)(2)(A) of 

the PRA (44 U.S.C. 3506(c)(2)(A)) 

requires Federal agencies to provide a 

60-day notice in the Federal Register

concerning each proposed collection of 

information before submitting the 

collection to OMB for approval. To 

comply with this requirement, FDA is 

publishing notice of the proposed 

collection of information set forth 

below.

FDA invites comments on these 

topics: (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 

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. Elsewhere, in 

this issue of the Federal Register, FDA 

is publishing a notice announcing an 

opportunity for public comment on the 

information collection, entitled 

‘‘Guidance on Consultation Procedures; 

Foods Derived from New Plant 

Varieties.’’

Recommendations for Early Food 

Safety Evaluation of New NonPesticidal Proteins Produced by New 

Plant Varieties Intended for Food Use

Since 1992, when FDA issued its 

Statement of Policy: Foods Derived from 

New Plant Varieties (57 FR 22984, May 

29, 1992), FDA has encouraged 

developers of new plant varieties, 

including those varieties that are 

developed through biotechnology, to 

consult with FDA early in the 

development process to discuss possible 

scientific and regulatory issues that 

might arise. The current guidance 

continues to foster early communication 

by encouraging developers to submit to 

FDA their evaluation of the food safety 

of their new protein. Such 

communication helps to ensure that any 

potential food safety issues regarding a 

new protein in a new plant variety are 

resolved early in development, prior to 

any possible inadvertent introduction 

into the food supply of material from 

that plant variety.

FDA believes that any food safety 

concern related to such material 

entering the food supply would be 

limited to the potential that a new 

protein in food from the plant variety 

could cause an allergic reaction in 

susceptible individuals or could be a 

toxin. This guidance describes the 

procedures for early food safety 

evaluation of new proteins in new plant 

varieties, including bioengineered food 

plants, and the procedures for 

communicating with FDA about the 

safety evaluation.

Information Collection Burden Estimate

FDA estimates the burden for this 

information collection as follows:

TABLE 1.—ESTIMATED REPORTING BURDEN1

No. of

Respondents

Annual

Frequency per 

Response

Total Annual

Responses

Hours per

Response

Operating and 

Maintenance 

Costs 

Total Hours 

First four data components 20 1 20 4 $0 80

Two other data components 20 1 20 16 $0 320

Annual one-time burden hours 400

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

Burden:

Hour Burden Estimate

One Time Burden

Completing an early food safety 

evaluation for a new protein from a new 

plant variety will be a one-time burden 

(one evaluation per new protein). FDA 

cannot know how many developers will 

choose to complete an early food safety 

evaluation for their new plant protein. 

Some plant developers may choose not 

to complete an evaluation because of the 

uncertainty of the new plant variety’s 

future viability in the marketplace. 

Other developers may have previously 

communicated with FDA about the food 

safety of a new protein, for example, 

when the same protein was expressed in 

a different crop. Still other developers 

may test a new plant variety under such

Federal Register / Vol. 69, No. 226 / Wednesday, November 24, 2004 / Notices 68383

conditions that those developers have 

no concerns that the new protein could 

enter the food supply.

FDA scientists predict that this draft 

guidance will generate about 20 to 150 

early food safety evaluations yearly. 

While there is uncertainty as to the 

number of developers who will choose 

to submit an evaluation, FDA estimates 

that the annual number of early food 

safety evaluations will be closer to the 

lower bound estimate of 20 evaluations 

rather than the upper bound estimate of 

150 evaluations. This estimation is 

supported by the fact that on average 

there have been nine initial 

biotechnology consultations per year; an 

initial biotechnology consultation has 

traditionally been the first discussion 

between a developer and FDA about a 

bioengineered food.

Evaluation Components

The early food safety evaluation for 

new proteins includes six main data 

components. Four of these data 

components are easily and quickly 

obtainable, having to do with the 

identity and source of the protein. FDA 

estimates that completing these data 

components will take about 4 hours per 

evaluation. In table 1 of this document, 

row 1 shows that for 20 evaluations, the 

total burden for these 4 data 

components is 80 hours.

Two data components ask for original 

data to be generated. One data 

component consists of a bioinformatics 

analysis which can be performed using 

publicly available databases. The other 

data component involves ‘wet’ lab work 

to assess the new protein’s stability and 

the resistance of the protein to 

enzymatic degradation using 

appropriate in vitro assays (protein 

digestibility study).

The paperwork burden of these two 

data components consists of the time it 

takes the company to put together the 

information on these two data 

components to submit to FDA. We 

estimate that these two data components 

will take 16 hours to complete (8 hours 

for each component). Table 1, row 2, 

shows that for 20 evaluations, the total 

burden for these two data components 

is 320 hours.

III. Comments

Interested persons may submit to the 

Division of Dockets Management (see 

ADDRESSES) written or electronic 

comments regarding the draft guidance 

and the collection of information 

provisions. Submit a single copy of 

electronic comments or two paper 

copies of any mailed comments, except 

that individuals may submit one paper 

copy. Comments are to be identified 

with the docket number found in 

brackets in the heading of this 

document. The draft guidance and 

received comments may be seen in the 

Division of Dockets Management 

between 9 a.m. and 4 p.m., Monday 

through Friday.

IV. Electronic Access

An electronic version of the draft 

guidance is available on the Internet at 

http://www.cfsan.fda.gov/guidance.html

and http://www.fda.gov/cvm.

Dated: November 17, 2004.

Jeffrey Shuren,

Assistant Commissioner for Policy.

[FR Doc. 04–26049 Filed 11–19–04; 1:52 pm]

BILLING CODE 4160–01–S

DEPARTMENT OF HEALTH AND 

HUMAN SERVICES

Food and Drug Administration

[Docket No. 2004D–0481]

Guidance for Industry and Food and 

Drug Administration Staff; Class II 

Special Controls Guidance Document: 

Newborn Screening Test Systems for 

Amino Acids, Free Carnitine, and 

Acylcarnitines Using Tandem Mass 

Spectrometry; Availability

AGENCY: Food and Drug Administration, 

HHS.

ACTION: Notice.

SUMMARY: The Food and Drug 

Administration (FDA) is announcing the 

availability of the guidance entitled 

‘‘Class II Special Controls Guidance 

Document: Newborn Screening Test 

Systems for Amino Acids, Free 

Carnitine, and Acylcarnitines Using 

Tandem Mass Spectrometry.’’ This 

guidance document describes a means 

by which newborn screening test 

systems for amino acids, free carnitine, 

and acylcarnitines using tandem mass 

spectrometry may comply with the 

requirements of special controls for 

class II devices. It includes 

recommendations for validation of 

performance characteristics and 

recommendations for product labeling.

Elsewhere in this issue of the Federal 

Register, FDA is publishing a final rule 

to classify newborn screening test 

systems for amino acids, free carnitine, 

and acylcarnitines using tandem mass 

spectrometry into class II (special 

controls). This guidance document is 

immediately in effect as the special 

control for newborn screening test 

systems for amino acids, free carnitine, 

and acylcarnitines using tandem mass 

spectrometry, but it remains subject to 

comment in accordance with the 

agency’s good guidance practices 

(GGPs).

DATES: Submit written or electronic 

comments on this guidance at any time. 

General comments on agency guidances 

are welcome at any time.

ADDRESSES: Submit written requests for 

single copies on a 3.5′′ diskette of the 

guidance document entitled ‘‘Class II 

Special Controls Guidance Document: 

Newborn Screening Test Systems for 

Amino Acids, Free Carnitine, and 

Acylcarnitines Using Tandem Mass 

Spectrometry’’ to the Division of Small 

Manufacturers, International, and 

Consumer Assistance (HFZ–220), Center 

for Devices and Radiological Health, 

Food and Drug Administration, 1350 

Piccard Dr., Rockville, MD 20850. Send 

one self-addressed adhesive label to 

assist that office in processing your 

request, or fax your request to 301–443–

8818. See the SUPPLEMENTARY

INFORMATION section for information on 

electronic access to the guidance.

Submit written comments concerning 

this guidance to the Division of Dockets 

Management (HFA–305), Food and Drug 

Administration, 5630 Fishers Lane, rm. 

1061, Rockville, MD 20852. Submit 

electronic comments to http://

www.fda.gov/dockets/ecomments. 

Identify comments with the docket 

number found in brackets in the 

heading of this document.

FOR FURTHER INFORMATION CONTACT:

Carol C. Benson, Center for Devices and 

Radiological Health (HFZ–440), Food 

and Drug Administration, 2098 Gaither 

Rd., Rockville, MD 20850, 301–594–

1243, ext. 144.

SUPPLEMENTARY INFORMATION:

I. Background

Elsewhere in this issue of the Federal 

Register, FDA is publishing a final rule 

classifying newborn screening test 

systems for amino acids, free carnitine, 

and acylcarnitines using tandem mass 

spectrometry into class II (special 

controls) under section 513(f)(2) of the 

Federal Food, Drug, and Cosmetic Act 

(the act) (21 U.S.C. 360c(f)(2)). This 

guidance document will serve as the 

special control for newborn screening 

test systems for amino acids, free 

carnitine, and acylcarnitines that utilize 

tandem mass spectrometry. Section 

513(f)(2) of the act provides that any 

person who submits a premarket 

notification under section 510(k) of the 

act (21 U.S.C. 360(k)) for a device that 

has not previously been classified may, 

within 30 days after receiving written 

notice classifying the device in class III 

under section 513(f)(1) of the act, 

request FDA to classify the device under 

the criteria set forth in section 513(a)(1)