Docket ID No. EPA-HQ-OPP-2006-0291

Response to Comments on the Guidance on Small-Scale Field Testing and
Low-Level Presence in Food of Plant-Incorporated Protectants (PIPs)

On September 29, 2006, the United States Environmental Protection Agency
(EPA) issued a Draft Pesticide Registration (PR) Notice entitled
Guidance on Small-Scale Field Testing and Low-level Presence in Food of
Plant-Incorporated Protectants (PIPs) for public comment.  The purpose
of the notice is to clarify (1) the process by which EPA reviews and
ensures the safety of residues of plant-incorporated protectants (PIPs)
potentially present in low levels in food or feed; and (2) the
conditions under which a tolerance or exemption from the requirement of
a tolerance would be required for field tests for biotechnology-derived
food and feed crop plants containing PIPs. PIPs are pesticidal
substances produced by plants, including the genetic material necessary
for the plant to produce the substance.  PIPs also include any other
ingredients, such as selective markers used to insert the active
ingredient into the plant.  In this document, EPA is responding to the
public comments received.     

The purpose of this PR Notice is to provide guidance to those
individuals conducting field trials with plant-incorporated protectants
that have either not received a registration or an EUP and do not have a
tolerance, temporary tolerance, or tolerance exemption established for
the trait being tested. Because the regulatory obligations are contained
in several different rules, the Agency is providing this guidance to
facilitate compliance and prevent potential violations caused by the
inadvertent spread of the test trait. PR Notice 2007-X summarizes,
explains, and provides guidance for using or testing plant-incorporated
protectants under the Federal Insecticide, Fungicide, and Rodenticide
Act (FIFRA) and the Federal Food, Drug, and Cosmetic Act (FFDCA). 

This guidance also is intended to reinforce coordination of EPA
regulatory efforts related to biotechnology products with those of the
Food and Drug Administration and of the USDA Animal and Plant Health
Inspection Service, as outlined under the Coordinated Framework for the
Regulation of the Products of Biotechnology (51 FR 23302, June 26,
1986).  

During the public comment period, EPA received 10 comments from the
following entities:

1.	Food Products Association (FPA) and Grocery Manufacturers Association

2.	American Seed Trade Association

3.	Biosafety Institute for Genetically Modified Agricultural Products
(BIGMAP), Iowa State University

4.	Monsanto

5.	National Grain and Feed Association

6.	AgBiotech Planning Committee

7.	Oregon State University

8.	Biotechnology Industry Organization (BIO)

9.	Pioneer

10.	B. Sachau

This PR Notice does not present new rules, policies, or interpretations,
but rather summarizes, explains, and provides guidance regarding
compliance with existing rules under FIFRA and FFDCA.  Several
commenters commended the Agency for providing this guidance.  Others
endorsed the continued implementation of measures designed to prevent
the occurrence of unregistered PIPs in the food supply.  Substantially
similar comments were consolidated into a single comment and responded
to below.   

Comment:  The Agency should make the voluntary consultation mandatory.  

EPA response:  This notice is intended to explain existing regulations
and does not contain any new policies.  Making consultation mandatory
would require rulemaking, which is beyond the scope of this notice. 
However, the Agency will take these comments under consideration for
potential regulatory changes in the future.

Comment:  Amend confinement standard from “minimizing” to “seek to
avoid.”

EPA response:  The Agency has amended section VII of the PR notice from
“minimize the possibility of pollen drift” to “seek to avoid
pollen drift.”

Comment:  EPA should acknowledge that the data are subject to the data
protection provisions of FQPA and FIFRA. 

EPA Response:  Data submitted to support an application for registration
under FIFRA or a petition for a tolerance or tolerance exemption under
FFDCA are subject to the data protection provisions in FIFRA 
§3(c)(1)(F) or §408(i), as appropriate. 

Comment:  FDA guidance to industry (Recommendations for the Early Food
Safety Evaluation of New Non-Pesticidal Proteins Produced by New Plant
Varieties Intended for Food Use) contains no explicit recommendation for
toxicity testing of proteins, whereas EPA suggests that acute oral
toxicity (maximum-hazard dose) studies be considered when a tolerance is
determined for the purpose of small-scale field tests. EPA should
clarify when acute oral toxicity tests and characterization of the
introduced gene may be needed for early food safety evaluations.  Also,
if a protein has fully undergone the FDA consultation process, the
protein should be recognized by EPA as having a temporary tolerance for
purposes of low-level presence.

EPA Response:  The commenter may have misunderstood the PRN.  EPA
included a discussion of the kinds of information that has previously
been submitted to the agency to establish temporary tolerances to help
the public understand what kind of data the Agency has previously relied
upon, but did not intend that discussion to resolve the question of
whether the listed data will be necessary for all PIPs.  EPA is in the
process of developing a rule to establish data requirements specific to
PIPs under Part 158, and as part of that process, will provide the
further clarification that the commenter is requesting.     

Regarding the commenter's other request, EPA’s statutory obligations
under section 408 of the FFDCA differ from FDA’s obligations under
FFDCA section 402.  As a preliminary matter, under section 408, EPA must
establish a temporary tolerance through the statutorily mandated
process, and may not simply "recognize" a protein as having a temporary
tolerance.  Moreover, under its consultation process, FDA does not make
a regulatory finding of safety.  Consequently, EPA does not believe that
it can determine in the abstract that the results of the consultation
process would necessarily suffice for EPA to establish a temporary
tolerance under section 408.  However, to the extent that the
information submitted to FDA as part of the consultation process is
sufficient to allow the Agency to determine that the protein meets the
FFDCA section 408 safety standard, no further data would need to be
provided to allow the Agency to establish the tolerance.  

 

Comment:  EPA should fully harmonize with USDA on notification and
permit measures as they relate to containment or confinement for EUPs of
more than 10 acres.

EPA guidance should be consistent with FDA and USDA positions with
respect to updated field test requirements and consistent approaches to
confinement of small-scale field trials. 

EPA response:  We are currently working on several initiatives for
expanded opportunities to harmonize to the extent possible with USDA and
FDA.  However, each Federal Agency has different statutory authorities,
which may necessitate different approaches.  

Comment:  EPA states “that the spread of pollen from the test corn in
the study to a sexually incompatible crop such as soybeans would neither
trigger the necessity for a tolerance or tolerance exemption nor an
EUP.” However, if pollen, crop dust, or seed from the experiment finds
its way to a lot of soybean (there are multiple routes for this to occur
due to production and processing of these crops), the protein may be
detectable at low levels.  EPA needs to be more explicit in their
consideration of such nature of off-field movement.

EPA response:  EPA’s example was intended to describe the regulatory
approach when there is clearly no concern for transfer of genetic
information (that is, between sexually incompatible plants). 
Containment measures (as specified in APHIS permits and in this PR
notice) and crop destruct must be used when there is no temporary
tolerance established.  Measures must be in place to preclude the
residues from escaping the experimental plot.  If the PIP escapes and is
detected, even if genetically modified pollen is admixed with another
crop, the product would be considered adulterated under FFDCA if there
is no tolerance in place.  The developer would have the legal liability
for such an infraction.

Comment:  The EPA and the U.S. government should continue to dialogue
with other countries on science-based decisions for low level presence
for those materials approved in U.S. but not yet approved in country of
import. A global standard that gives guidance in situations of low level
contamination is encouraged and would be valuable to the industry.
Asynchronous approval results in a zero tolerance for US agricultural
exports.

EPA response:  EPA agrees with this comment and is working on several
initiatives to coordinate and harmonize globally, such as North American
Biotechnology Initiative (NABI) and CODEX.

Comment:  At times, it is difficult to discern whether the Agency is
referring to regulatory requirements or is referring to non-binding
recommendations. It is recommended that EPA more explicitly clarify
which parts of the PR Notice actually serve as guidance.  In addition,
we suggest that EPA clarify when off-field movement of a PIP
necessitates tolerance, tolerance exemption, or an Experimental Use
Permit (EUP).

EPA response:  The entire PR Notice is guidance.  To the extent the PR
Notice refers to mandatory requirements, it is describing requirements
under FIFRA or our regulations at 40 CFR Parts 150 to 189.  In the
notice, words such as may indicate guidance and words such as must refer
to a statutory or regulatory requirement.  Specifically, off-field
movement of a PIP trait always requires a tolerance or a tolerance
exemption when the PIP might be found in food or feed, intentionally or
unintentionally.  An EUP with stringent containment or confinement
measures can be issued without a tolerance.  For a complete explanation
of the regulation, consult 40 CFR 172.  If a potential applicant desires
additional information or has any questions, they are encouraged to
consult directly with EPA.

Comment:  EPA should clarify what different approach (if any) will be
applied for experiments that are conducted on larger acreages under an
EUP; since under an EUP – where only a temporary tolerance is in place
– escape of genetic material could pose problems if the product did
not proceed to full registration. 

EPA Response:  When EPA grants an EUP, a temporary tolerance is
established to cover the time period of the trial and as long as
necessary to allow the food to pass through the channels of trade.  The
Agency takes these factors into consideration in its reviews of  very
large scale EUPs, including asking a developer to justify the need for
very large acreages to produce the data to support a registration.  Such
a tolerance could be extended if necessary.  EPA recommends researchers
use appropriate containment procedures to prevent gene escape until
adequate safety data are produced and evaluated that would support any
necessary tolerance.  This PR notice is intended to explain the
regulations and provide guidance to developers to preclude the escape of
genetic material and a potential violation.   

Comment:  When describing production systems for biotechnology-derived
plants, USDA distinguishes between containment (closed production
systems, such as greenhouse or laboratory settings) and confinement
(production in an open-field environment). In the present guidance, EPA
uses the term containment exclusively when they are referring
principally to open-field production systems. We encourage the use of
terminology in a consistent manner between USDA and EPA.

EPA response:  To enhance harmonization and ensure clarity to
stakeholders, EPA will move to adopt the terms containment and
confinement as used by USDA.

Comment:  EPA should grant a tolerance or exemption from tolerance for a
protein broadly across crops, rather than on a crop-by-crop basis. 

EPA Response:  A registrant has the option of requesting a tolerance or
tolerance exemption for any and all food commodities in the tolerance
petition. Thus, the registrant could request a tolerance exemption that
applies broadly across crops.  The petition would need to include all
data necessary to support the decision for the scope of the request.

Comment:  The Agency should evaluate the adequacy of buffer strips
between experimental use crops and commercial crops to prevent cross
contamination; consider providing prenotification of biotech trials to
adjacent farms; and  follow-up to ensure crop destruct to ensure grain
does not commingle.

EPA Response:  The Agency evaluates the experimental design in the
application, including factors such as the adequacy of the buffer
strips, in making its determination to issue the EUP.  Prenotification
for EUPs is provided to state authorities by EPA Regional Offices prior
to EUPs being conducted.  However, if the location is claimed as
confidential, EPA could not disclose the information to the state or to
adjacent farms unless the Agency determines that the information is not
entitled to confidential treatment.  The Agency relies on periodic
inspection by enforcement officials and the cooperative efforts of other
Federal Agencies to ensure that mitigation measures are enforced and
maintain the safety of the food supply and the environment.

Comment:  EPA should make public the procedures and standards developers
would use to judge whether they might or might not anticipate residues
in food and feed of PIPs undergoing experimental field trials.  The
Agency should provide examples of confinement and quality control
measures that are needed for new proteins.  These measures should
provide clearly defined specifications, with a commensurate stipulation
that researchers and developers use the most appropriate management,
control, and containment practices to prevent PIPs that have not
completed the full regulatory review from entering the food and feed
supply. 

EPA response:  As stated in the PR notices, registrants or researchers
must conduct small scale field trials in a manner that prevents
dispersal of PIPs and PIP residues into the food and feed supply.  The
data EPA relies on to make determinations on whether to grant an EUP are
available in the public docket except for certain genetic transformation
data.  Factors such as the crop being tested, the conditions of the
trial, and the location of the trial all factor into the extent of the
mitigation measures used.  Due to the inherent differences in the
various trials, EPA does not prescribe a single set of measures.  This
notice lists examples of several measures that may be used, and it is
the responsibility of the investigator to use his or her best
professional judgment in implementing effective mitigation measures. 
The Agency is available for consultation and may be contacted for any
questions.    

Comment:  The Notice should explicitly state that tolerances are needed
on imported food and feed also.

EPA response:  A sentence has been added to section B. FFDCA Section 408
Requirements of the notice explicitly stating the requirement for import
tolerances.

Comment:  The PR notice states that “if a developer choose not to
destroy or hold the crops for additional testing, an EUP would be
required for any testing under 10 acres unless a tolerance …had been
established….”  This is confusing, as it could be interpreted to
suggest that an EUP without any conditions could be obtained in
situations where less than 10 acres of crop is planed, without crop
destruct or held for testing, and without a tolerance or exemption from
tolerance. Add “with appropriate conditions” after the two
references to an EUP on final paragraph of page 4 to clarify.

EPA response:  This change was made.

Comment:  In the discussion regarding when the 10-acre rule applies, the
notice leaves out key references to the timing of the tests.  Both time
and locality are covered in the rule. 

EPA response:  We have made a change in the second paragraph of section
C.  Small Scale Field Testing of Pesticides to add the time element to
the notice. 

Comment:  Insert the word protein in the discussion for characterization
data (that is, protein sequence data). 

EPA response:  This level of specificity is not needed, as EPA could
require either protein or DNA sequence data. Therefore, no change was
made. 

Comment:  In accordance with the Paperwork Reduction Act Notice, EPA
estimated the total annual respondent paperwork burden associated with
the application process for EUPs is 10.10.  The respondent commented
that the estimated total time required (time reading the regulations,
planning the necessary data collection activities, conducting tests,
analyzing data, generating reports and completing other required
paperwork, and storing, filing, and maintaining the data) is actually
1000 hours.

EPA response:  The EPA appreciates this comment, but without further
details regarding the estimated 1000 hours, we do not believe that we
have a basis for revising the estimate presented in the current
Information Collection Request (ICR).  That ICR recently underwent
public review and comment as part of its three-year renewal cycle and
EPA did not receive any similar comments about the estimated burden of
10.10 hours per application (71 FR 62436, 10/25/06).  The estimate
provided in the ICR is based on historical data on the EUP applications
received by EPA in fiscal years 2003, 2004 and 2005, and an estimated
burden for each of the following specifically identified paperwork
activities: Read regulations, Plan activities, Create information,
Gather information, Compile and review, Complete paperwork,
Store/maintain data.  Under the Paperwork Reduction Act, this ICR must
be reviewed and its approval sought anew every three years.  The Agency
will endeavor to further evaluate the commenter’s suggestion that the
per application burden may be higher than estimated.  These efforts will
be directed to the next renewal of the ICR.

		  DATE \@ "M/d/yyyy"  4/26/2007 

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