Federal Register / Vol. 74, No. 12 / Wednesday, January 21, 2009 / Notices 3615 

the agency must be accompanied by the 

certification. On April 18, 2008, FDA 

published a draft guidance on the 

certification requirement. In the draft 

guidance FDA provided a list of the 

types of submissions and applications 

that typically did not need to be 

accompanied by a certification. We 

received a number of comments to the 

docket concerning whether a 

certification should accompany the 

types of submissions and applications 

listed in the draft guidance, as well as 

other types of documents and 

information submitted to FDA. We also 

received a number of comments on this 

issue during the process for obtaining 

clearance under the Paperwork 

Reduction Act of 1995 (44 U.S.C. 3501– 

3520) for the certification form itself. In 

addition, FDA also has had more 

experience with the submission of the 

certification form since the form was 

implemented. 

The comments we received in 

response to the draft guidance and the 

development of the certification form, 

the inquiries to the agency, and our 

evolving experience caused us to 

reconsider our initial approach of 

identifying those documents and 

information that did not need to be 

accompanied by a certification. Instead, 

we concluded that it was more useful to 

identify those applications and 

submissions that must be accompanied 

by a certification. This approach is also 

consistent with many of the comments, 

which asked that we provide more 

specific information than was included 

in the draft guidance. Thus, we intend 

to exercise enforcement discretion 

concerning the submission of a 

certification with certain categories of 

applications and submissions to FDA, as 

noted in the guidance. 

This guidance describes FDA’s 

current thinking, for purposes of 

implementing Title VIII of FDAAA, 

regarding specific types of applications 

and submissions submitted to FDA 

under section 505, 515, 520(m), or 

510(k) of the act, or under section 351 

of the PHS Act, and accompanying 

certifications described in section 

402(j)(5)(B) of the PHS Act, 42 U.S.C. 

282(j)(5)(B). We note that the Agency’s 

discussion of ‘‘applications’’ and 

‘‘submissions’’ in this guidance is not 

necessarily applicable to any other 

provision of law. In determining how to 

interpret the certification requirement, 

FDA has focused on the plain language 

of Title VIII of FDAAA, as well as 

information that Title VIII is intended to 

capture. 

This guidance is being issued 

consistent with FDA’s good guidance 

practices regulation (21 CFR 10.115). 

The guidance represents the agency’s 

current thinking regarding the 

certification requirement in section 

402(j)(5)(B) of the PHS Act (42 U.S.C. 

282(j)(5)(B)). It does not create or confer 

any rights for or on any person and does 

not operate to bind FDA or the public. 

An alternative approach may be used if 

such approach satisfies the 

requirements of applicable statutes and 

regulations. 

II. Comments 

Interested persons may, at any time, 

submit to the Division of Dockets 

Management (see ADDRESSES) written or 

electronic comments regarding the 

guidance. 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. A copy of the guidance and 

received comments are available for 

public examination in the Division of 

Dockets Management between 9 a.m. 

and 4 p.m., Monday through Friday. 

III. Paperwork Reduction Act of 1995 

This guidance refers to a previously 

approved collection of information. This 

collection of information is subject to 

review by the Office of Management and 

Budget (OMB) under the Paperwork 

Reduction Act of 1995 (44 U.S.C. 3501– 

3520). The collection of information has 

been approved under OMB Control No. 

0910–0616. 

IV. Electronic Access 

Persons with access to the Internet 

may obtain the guidance document at 

eitherhttp://www.fda.gov/oc/initiatives/ 

advance/fdaaa.html or http:// 

www.regulations.gov. 

Dated: January 15, 2009. 

Jeffrey Shuren, 

Associate Commissioner for Policy and 

Planning. 

[FR Doc. E9–1183 Filed 1–15–09; 11:15 am] 

BILLING CODE 4160–01–S 

DEPARTMENT OF HEALTH AND 

HUMAN SERVICES 

Food and Drug Administration 

[Docket No. FDA–2009–N–0018] 

Report of Quantitative Risk and Benefit 

Assessment of Commercial Fish 

Consumption, Focusing on Fetal 

Neurodevelopmental Effects 

(Measured by Verbal Development in 

Children) and on Coronary Heart 

Disease and Stroke in the General 

Population, and Summary of Published 

Research on the Beneficial Effects of 

Fish Consumption and Omega-3 Fatty 

Acids for Certain Neurodevelopmental 

and Cardiovascular Endpoints; 

Availability 

AGENCY: Food and Drug Administration, 

HHS. 

ACTION: Notice. 

SUMMARY: The Food and Drug 

Administration (FDA) is announcing the 

availability of two draft documents. The 

first is entitled ‘‘Report of Quantitative 

Risk and Benefit Assessment of 

Commercial Fish Consumption, 

Focusing on Fetal Neurodevelopmental 

Effects (Measured by Verbal 

Development in Children) and on 

Coronary Heart Disease and Stroke in 

the General Population’’ (draft risk and 

benefit assessment report). The draft 

risk and benefit assessment report 

describes an analysis done by FDA that 

results in quantitative estimates of the 

net effect on fetal neurodevelopment in 

children of maternal consumption of 

commercial fish, as measured by verbal 

development and the net effect of eating 

commercial fish on coronary heart 

disease and stroke in the general 

population. Effects with respect to each 

of these health endpoints has been 

associated in the scientific literature 

with methylmercury exposure (which 

primarily occurs through fish 

consumption) and with the 

consumption of fish and of omega-3 

fatty acids, which are found in fish. The 

second draft document entitled 

‘‘Summary of Published Research on the 

Beneficial Effects of Fish Consumption 

and Omega-3 Fatty Acids for Certain 

Neurodevelopmental and 

Cardiovascular Endpoints’’ (draft 

summary of published research) is a 

compendium of research prepared by 

FDA for use in developing its 

quantitative risk and benefit assessment. 

When peer and public review are 

complete, the draft risk and benefit 

assessment report and the draft 

summary of published research are 

intended to add to the growing body of 

scientific literature investigating the 

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3616 Federal Register / Vol. 74, No. 12 / Wednesday, January 21, 2009 / Notices 

likelihood, magnitude, and direction of 

health impacts linked to consumption of 

commercial fish. FDA is seeking public 

comment on the draft risk and benefit 

assessment report and the draft 

summary of published research. 

DATES: Comments on the draft risk and 

benefit assessment and on the draft 

summary of published research must be 

submitted by April 21, 2009. 

ADDRESSES: Submit written comments 

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.regulations.gov. 

FOR FURTHER INFORMATION CONTACT: 

Philip Spiller, Center for Food Safety 

and Applied Nutrition (HFS–002), Food 

and Drug Administration, 5100 Paint 

Branch Pkwy., College Park, MD 20740– 

3835, 301–436–1428, FAX 301–436– 

2668, e-mail: Philip.Spiller@fda.hhs.gov. 

SUPPLEMENTARY INFORMATION: 

I. Background 

Fish provides protein, is low in 

saturated fat, and is rich in many 

micronutrients; it also can be a source 

of certain omega-3 fatty acids. As the 

Institute of Medicine of the National 

Academies of Science (IOM) noted in a 

recent report, ‘‘[i]n the past several 

years, research has implicated seafood, 

particularly its contribution of EPA and 

DHA [two omega-3 fatty acids], in 

various health benefits identified for the 

developing fetus and infants, and also 

for adults, including those at risk for 

cardiovascular disease.’’ (Institute of 

Medicine, Committee on Nutrient 

Relationships in Seafood: Selections to 

Balance Benefits and Risks. Seafood 

Choices: Balancing Benefits and Risk. 

2006, National Academy of Sciences, at 

1). However, as a result of natural 

processes and human activity, aquatic 

food sources, including fish, can contain 

methylmercury, which has been linked 

to adverse health consequences. 

Because of the presence of 

methylmercury in fish, FDA and the 

U.S. Environmental Protection Agency 

(EPA) issued an advisory to consumers, 

‘‘What You Need to Know About 

Mercury in Fish and Shellfish’’ (http:// 

www.cfsan.fda.gov/~dms/ 

admehg3.html). The advisory, which 

was most recently revised in 2004, 

recommends that women who may 

become pregnant, pregnant women, 

nursing mothers, and young children 

avoid some types of fish and eat fish 

and shellfish that are lower in 

methylmercury, as specified in more 

detail in the advisory. 

Researchers in the United States and 

elsewhere have attempted in recent 

years to develop approaches to better 

evaluate the net health impacts of fish 

consumption; in other words, to 

understand the relationship between the 

risk of not eating fish (and thus losing 

any health benefits fish may provide) 

and the risk of eating fish that contains 

methylmercury at the levels currently 

found in the commercial fish available 

to consumers. As the IOM noted in its 

2006 report, ‘‘A better way is needed to 

characterize the risks combined with the 

benefits analysis.’’ (IOM 2006 at 6). The 

draft summary of published research 

and the draft risk and benefit 

assessment report were developed by 

FDA to provide further scientific 

information to help address this 

question for consumers of commercial 

seafood in the United States (i.e., fish 

shipped or sold interstate, as opposed to 

fish caught recreationally or for 

subsistence). 

The draft risk and benefit assessment 

report reflects an effort by FDA to 

quantify the impact of eating 

commercial fish on three human health 

endpoints: (1) Neurodevelopment, as 

measured by verbal development in 

childhood as assessed by the effect of 

prenatal exposure to methylmercury as 

passed from the mother to the 

developing fetus; (2) risk of fatal 

coronary heart disease; and (3) risk of 

fatal stroke. Each of these health 

endpoints has been associated in the 

scientific literature both with adverse 

effects of methylmercury exposure 

(including through fish consumption) 

and beneficial effects of regular fish 

consumption. The draft risk and benefit 

assessment report provides further 

scientific information about the 

likelihood and magnitude of either 

beneficial or adverse net effects on 

health at current levels of commercial 

fish consumption and exposure to 

methylmercury through fish 

consumption in the United States. The 

draft risk and benefit assessment report 

should not be construed as altering the 

existing fish advisory. Moreover, 

because this assessment does not 

distinguish among types of fish in terms 

of their beneficial constituents, it is not 

possible to translate the results of this 

analysis into fish-specific advice to 

consumers about maximizing benefits. 

The methodology used for the 

quantitative risk and benefit assessment 

is novel for FDA in that, rather than 

attempting to quantify the risk resulting 

from the presence of a particular hazard 

in a food, it estimates that risk and the 

benefit from consumption of the food in 

the same quantitative analysis. For fetal 

neurodevelopment, the assessment 

estimates this net effect by separately 

estimating: (1) The likelihood and size 

of an adverse contribution from 

methylmercury to the net effect; (2) the 

likelihood and size of a beneficial 

contribution to the net effect from fish; 

and (3) the likelihood, size, and 

direction of the net effect. For the 

methylmercury contribution, the 

assessment uses data to derive modeling 

estimates of the association between 

methylmercury and early age verbal 

skills (as an indicator of 

neurodevelopment) and then compares 

the results against results developed 

elsewhere on methylmercury’s effect on 

other aspects of neurodevelopment, 

including intelligence quotient (IQ). For 

the fish contribution, the assessment 

uses data to derive modeling estimates 

of the association between fish 

consumption during pregnancy and 

early age verbal skills. For the net effect, 

the assessment combines the results 

from the methylmercury and fish 

contributions. This draft risk and benefit 

assessment report builds on published 

work performed previously by FDA 

scientists on the estimation of a 

methylmercury effect, as well as recent 

articles by other investigators that have 

quantitatively assessed this effect. For 

fatal coronary heart disease and stroke, 

the assessment estimates the net effect 

on risk from fish consumption without 

separately modeling a methylmercury 

contribution and a fish contribution. 

Most data on this subject come from 

studies that measured an association 

between fish consumption and these 

health endpoints without measuring a 

methylmercury contribution. The 

modeling builds in part on doseresponse functions for these endpoints 

that have been published in the 

scientific literature. 

The draft risk and benefit assessment 

report identifies and discusses 

assumptions made for the scientific 

models and analyses and sources of 

uncertainty with respect to each 

endpoint analyzed. Subject to the 

limitations and assumptions set forth in 

the analysis, the risk and benefit 

assessment estimated the net impact of 

consumption of different amounts of 

fish. For example, with respect to fetal 

neurodevelopment, we modeled various 

‘‘what if’’ scenarios, in which we 

estimated what would happen if women 

of child-bearing age ate more or less 

fish, or if the amount of methylmercury 

in the fish they ate were reduced. 

The results indicate that consumption 

of fish species that are low in 

methylmercury has a significantly 

greater probability of resulting in a net 

benefit, as measured by verbal 

development. The highest net benefit 

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Federal Register / Vol. 74, No. 12 / Wednesday, January 21, 2009 / Notices 3617 

modeled in our risk and benefit analysis 

was modest. When we modeled actual 

baseline consumption for the range of 

methylmercury concentrations (low to 

high) the assessment indicated a 

significant probability of a net adverse 

effect for 1/10 of 1 percent of children 

for the central estimate. The highest 

estimated net adverse effect was also 

quite modest. For fatal coronary heart 

disease and stroke, commercial fish 

baseline consumption is averting a 

central estimate of over 30,000 deaths 

per year from coronary heart disease 

and over 20,000 deaths per year from 

stroke. The results of our quantitative 

risk and benefit assessment are 

generally consistent with research 

reported in recent years in the scientific 

literature. 

The draft summary of published 

research identifies primarily secondary 

analyses of the large body of scientific 

research on the impact of fish and 

omega-3 fatty acids on cardiovascular 

and neurologic endpoints, including 

research on both prenatal and post-natal 

exposures. In addition to the IOM 

report, these secondary analyses include 

reports by the American Heart 

Association, the European Food Safety 

Authority, the International Society for 

the Study of Fatty Acids and Lipids, the 

World Health Organization and a 

previous investigation by FDA. This 

compendium of research was developed 

by FDA for use in developing its 

quantitative risk benefit assessment and 

provides background for that document. 

The draft summary of published 

research identifies and delineates the 

lines of scientific evidence that indicate 

the association of fish and omega-3 fatty 

acid consumption with cardiovascular 

and neurodevelopmental health 

outcomes. When available, the 

compendium of research also identifies 

reports of quantitative dose-response 

relationships which may be relevant for 

risk and benefit assessment modeling. 

The draft summary of published 

research describes the context of the 

overall body of scientific evidence 

currently available for potential 

application to the risk and benefit 

assessment modeling and the draft risk 

and benefit assessment report. 

The agency designated the draft risk 

and benefit assessment report and the 

draft summary of published research as 

a ‘‘highly influential scientific 

assessment’’ under the Office of 

Management and Budget’s (OMB) Final 

Information Quality Bulletin for Peer 

Review (the Bulletin) (70 FR 2664, 

January 14, 2005). In August 2008, FDA 

submitted a draft of the risk and benefit 

assessment report (which at the time 

also incorporated the draft summary of 

published research) to seven scientific 

experts outside the Federal Government, 

from a range of scientific disciplines, for 

purposes of obtaining each expert’s 

independent, written peer review. The 

draft risk and benefit assessment report 

and the draft summary of published 

research that are being made available 

for public comment reflect revisions 

made to date in response to the peer 

reviewers’ comments and suggestions. 

The Information Quality Act Bulletin for 

Peer Review requires FDA to post at its 

Web site a report of the peer review that: 

(1) Contains the names and credentials 

of the peer reviewers; (2) sets forth the 

‘‘charge,’’ i.e., the scientific questions 

asked of the reviewers; (3) provides the 

verbatim comments submitted by each 

reviewer (without attribution); and (4) 

discusses what FDA has done to the 

documents in response to the peer 

reviewers’ comments. We have posted at 

our Web site an interim draft of this 

report that provides this information at 

http://www.cfsan.fda.gov/~dms/ 

mehg109.html, although we expect and 

plan to finalize this report after revising 

our draft risk and benefit assessment 

report and the draft summary of 

published research, in response to 

further expert and peer review 

comments. 

Separately, FDA solicited and 

received comments from scientists at 

other Federal agencies, including EPA, 

the National Institutes of Health, the 

Centers for Disease Control and 

Prevention, and the National Oceanic 

and Atmospheric Administration during 

a review coordinated by OMB. The draft 

risk and benefit assessment report and 

the draft summary of published research 

being made available for comment have 

been revised to reflect revisions made in 

response to the inter-agency reviewers’ 

comments. 

At the same time we are making these 

draft documents available for public 

comment, we plan to provide a revised 

draft to the original peer reviewers to 

enable them to submit any further 

comments. We will revise the draft risk 

and benefit assessment report and the 

draft summary of published research as 

necessary after considering the public 

comments and any additional comments 

from the independent peer reviewers. 

We also plan to provide the revised 

version of the documents, a summary of 

the public comments that address 

significant scientific issues, and the 

external peer review report to an FDA 

scientific advisory committee. 

After public and advisory committee 

review of these documents are 

complete, appropriate risk management 

actions will then be considered on the 

basis of currently available scientific 

information. The release of these 

documents for public comment and peer 

review do not in any way modify the 

recommendations set forth in the 2004 

advisory on fish consumption. 

II. Comments 

Interested persons may submit to the 

Division of Dockets Management (see 

ADDRESSES) written or electronic 

comments regarding this document. 

Submit a single copy of electronic 

comments or two paper copies of any 

mailed comments, except that 

individuals may submit one paper copy. 

Comments are to be identified with the 

docket number found in brackets in the 

heading of this document. Received 

comments may be seen in the Division 

of Dockets Management between 9 a.m. 

and 4 p.m., Monday through Friday. 

III. Electronic Access 

The draft documents described in this 

notice are available electronically at 

http://cfsan.fda.gov/~dms/ 

mehg109.html. 

IV. Access to Related Documents 

All references listed in the reports are 

available in FDA’s Division of Dockets 

Management (see ADDRESSES). Computer 

programs used in the risk and benefit 

assessment modeling are available from 

Clark Carrington, Center for Food Safety 

and Applied Nutrition (HFS–301), Food 

and Drug Administration, 5100 Paint 

Branch Pkwy., College Park, MD 20740– 

3835, 301–436–1947, e-mail: 

Clark.Carrington@fda.hhs.gov. 

Dated: January 14, 2009. 

Jeffrey Shuren, 

Associate Commissioner for Policy and 

Planning. 

[FR Doc. E9–1081 Filed 1–15–09; 11:15 am] 

BILLING CODE 4160–01–S 

DEPARTMENT OF HEALTH AND 

HUMAN SERVICES 

Food and Drug Administration 

[Docket No. FDA–2008–N–0658] 

Risk Assessment of the Public Health 

Impact From Foodborne Listeria 

monocytogenes in Some Ready-to-Eat 

Foods Sliced, Prepared, and/or 

Packaged in Retail Facilities; Request 

for Comments and for Scientific Data 

and Information 

AGENCY: Food and Drug Administration, 

HHS. 

ACTION: Notice; request for comments 

and for scientific data and information. 

SUMMARY: The Food and Drug 

Administration (FDA) is requesting 

mstockstill on PROD1PC66 with NOTICES