Special Issue Editorial

Impact of Genomic Technologies on RegulatoryPoliciesçPresentations at the 37th Annual Meeting of

the Environmental Mutagen Society

Kerry L. Dearfield1* and James C. Fuscoe2

1U.S. Department of Agriculture, Food Safety and Inspection Service,Office of Public Health Science, Washington, District of Columbia

2U.S. Food and Drug Administration, National Center for Toxicological Research,Division of System Toxicology, Jefferson, Arkansas

Escalating amounts of information and a panoply of meth-

odologies emanating from genomics research are clearly

impacting the disciplines of toxicology and public health.

As greater insight from these technologies, which also

includes proteomics and metabonomics, is obtained, there

is increasing focus and pressure on regulatory agencies to

evaluate the utility and validity of information generated

using \omics" technologies. Many agencies (e.g., US

Food and Drug Administration, US Department of Agri-

culture, US Environmental Protection Agency) have been

addressing many of the issues raised by omics technolo-

gies, and the 37th Annual Meeting of the Environmental

Mutagen Society (EMS) provided an opportunity to col-

lectively review the strategic plans of various governmen-

tal agencies regarding the use of omics data in regulatory

toxicology. The symposium entitled \Impact of Genomic

Technologies on Regulatory Policies" was held in Sep-

tember 2006 in Vancouver, Canada. In addition, a special

workshop entitled \Progress in Omics Technologies" was

convened to highlight specific technological advances.

This special edition of Environmental and Molecular Mu-tagenesis includes a collection of manuscripts based on

presentations from these sessions, which collectively out-

line the impact of omics technologies on regulatory pro-

grams and policies.

We were extremely fortunate to have excellent repre-

sentation from the many regulatory agencies including the

U.S. Food and Drug Administration (FDA), the U.S.

Environmental Protection Agency (EPA), the U.S. Depart-

ment of Agriculture (USDA), and Health Canada. Com-

plementary perspectives from industry and academia out-

lined how omics technologies impact risk assessment and

provide mechanistic insight, activities that are important

to government regulatory agencies.

In response to the challenges presented by omics tech-

nologies, several regulatory policies, positions, and gui-

dances have been issued from regulatory agencies (e.g.,

FDA and EPA), and these are discussed in the manu-

scripts by Goodsaid and Frueh and Benson et al.

Although the USDA and Health Canada have not issued

policies per se, they are actively examining the technol-

ogy. Their perspectives are presented in manuscripts by

Withee and Dearfield and Yauk and Berndt. Briefly, Fed-

erico Goodsaid of FDA’s Genomics Group presented

FDA’s Voluntary Genomics Data Submission process that

has been in place for 2 years, and addresses the need for

informal interactions between sponsors and regulators to

evaluate exploratory data with no immediate regulatory

impact. From the 25 submissions and 17 sponsor meet-

ings, a best practices document was developed. William

Benson of the EPA Office of Research and Development

described two aspects of EPA’s evaluation of genomics

and related technologies. The first part focused on the reg-

ulatory position that EPA has taken over the past few

years in its Genomics Interim Policy, and the newly

drafted Interim Guidance for Microarray-Based Assays.

The second part examined some of EPA’s efforts to apply

This manuscript represents the views of the authors. The contents do not

necessarily reflect the views or policies of their agencies, nor does men-

tion of trade names or commercial products constitute endorsement or

recommendation for use.

*Correspondence to: Kerry L. Dearfield, PhD, U.S. Department of Agri-

culture, Food Safety and Inspection Service, Office of Public Health Sci-

ence, Washington, DC 20250-3700, USA.

E-mail: kerry.dearfield@fsis.usda.gov

Received 10 January 2007; provisionally accepted 11 April 2007; and in

final form 12 April 2007

DOI 10.1002/em.20311

Published online in Wiley InterScience (www.interscience.wiley.com).

VVC 2007Wiley-Liss, Inc.

Environmental andMolecular Mutagenesis 48:347^348 (2007)

genomics results to the assessment of ecological risk. The

presentation by Kerry Dearfield of the USDA’s Food

Safety and Inspection Service focused on the use of

genomics technologies to efficiently identify food-borne

pathogens, and employ genomics information to investi-

gate pathogen–host interactions.

Quality assurance/quality control (QA/QC) systems for

the generation, handling, and distribution of genomics data

are of utmost importance to regulatory agencies. QA/QC

issues are always a major component of the data review

process, and genomics data evaluated in a regulatory con-

text must be of the highest possible quality. James Fuscoe

of FDA’s Division of Systems Toxicology at the National

Center for Toxicological Research outlined how QA/QC

metrics and thresholds are essential in order for genomics

data to provide the anticipated regulatory insight. The

Microarray Quality Control project, a major step in demon-

strating the reliability and consistency of microarray data,

is described in his contribution. The presentation by Carole

Yauk of Health Canada’s Safe Environments Program dis-

cussed current genomics research and development efforts,

including recent work that empirically evaluated the cross-

platform comparability of DNA microarray data. Yauk and

Berndt’s contribution stresses the importance of standardi-

zation to achieve reproducible and consistent results. More-

over, they outline critical steps in the microarray research

process, and highlight those that are critical for the genera-

tion of high-quality data.

Veronique Thybaud of the Drug Safety Evaluation

group of Sanofi-Aventis presented an industry perspective

that describes the potential impact of genomics technolo-

gies on genetic toxicity testing for regulatory purposes.

Thybaud et al.’s contribution outlines how toxicogenom-

ics can help improve the interpretation of positive in vitro

genotoxicity results and identify the appropriate direction

for subsequent research. In addition, they comment on the

use of genomics results to discriminate between DNA-re-

active compounds and non-DNA reactive compounds, as

well as between genotoxic and nongenotoxic carcinogens.

Much of this \mode of action" information can subse-

quently be employed to provide a better understanding of

mechanism of action for drug candidates, and moreover,

assess the utility and relevance of standard genetic toxic-

ity tests for assessment of human risk.

Ken Ramos of the University of Louisville Health Sci-

ences Center provided an academic perspective, and his

contribution described elegant research that illustrates

how genomics results can be employed to unravel com-

plex biological responses, and this information can subse-

quently be evaluated in a regulatory context. Ramos

et al.’s work shows that gene expression profiles can be

employed to identify relevant components of the biologi-

cal response to aryl hydrocarbon receptor (Ahr) ligands,

and that Ahr plays a key role in kidney development. The

functional genomics approach, which integrates gene ex-

pression and metabolite profile data with experimental

observations of the manipulated system, proved essential

for unraveling the role of Ahr in kidney disease.

The special workshop, which was cochaired by Yauk

and Thybaud, provided the latest information on techno-

logical advancements and applications in the omics fields,

including information on integration across technologies

and regulatory implications of omics results. More to the

point for this special issue, the workshop concluded with

a round table discussion that evaluated several issues that

will impact future directions and regulatory policies.

Data-sharing is clearly a major concern, as is the develop-

ment of resources to apply high-throughput tools for a

systems biology approach. The identified needs included

enhanced data curation capabilities, more comprehensive

and standardized experimental protocols, and increased

database storage facilities. The amount of data generated

will continue to grow in both size and scope, and there is

a definite need to develop a stronger public repository

infrastructure. The contribution by Michael Waters, for-

merly of the National Institute for Environmental Health

Sciences, and Yauk, expands on these issues.

We are extremely pleased to provide this special issue

outlining the current impact of genomics technologies on

regulatory research and policies. Omics technologies are

growing extraordinarily rapidly and the regulatory agen-

cies need to remain properly informed and sufficiently

flexible. Moreover, the exchanges and dialogue between

various regulatory agencies in several countries, as well

as academic and industrial researchers, that is promoted

by the symposium, the workshop, and this special issue

are crucial for the continuing evaluation of omics technol-

ogies.

Environmental and Molecular Mutagenesis. DOI 10.1002/em

348 Dearfield and Fuscoe