[Federal Register: February 10, 2006 (Volume 71, Number 28)]
[Notices]
[Page 7048-7051]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr10fe06-83]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
[Docket No. 2004D-0369]
Agency Information Collection Activities; Submission for Office
of Management and Budget Review; Comment Request; Recommendations for
the Early Food Safety Evaluation of New Non-Pesticidal Proteins
Produced by New Plant Varieties Intended for Food Use
AGENCY: Food and Drug Administration, HHS.
ACTION: Notice.
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SUMMARY: The Food and Drug Administration (FDA) is announcing that a
proposed collection of
[[Page 7049]]
information has been submitted to the Office of Management and Budget
(OMB) for review and clearance under the Paperwork Reduction Act of
1995 (the PRA).
DATES: Fax written comments on the collection of information by March
13, 2006.
ADDRESSES: OMB is still experiencing significant delays in the regular
mail, including first class and express mail, and messenger deliveries
are not being accepted. To ensure that comments on the information
collection are received, OMB recommends that comments be faxed to the
Office of Information and Regulatory Affairs, OMB, Attn: Fumie Yokota,
Desk Officer for FDA, FAX: 202-395-6974.
FOR FURTHER INFORMATION CONTACT: Jonna Capezzuto, Office of Management
Programs (HFA-250), Food and Drug Administration, 5600 Fishers Lane,
Rockville, MD 20857, 301-827-4659.
SUPPLEMENTARY INFORMATION: In compliance with 44 U.S.C. 3507, FDA has
submitted the following proposed collection of information to OMB for
review and clearance.
Recommendations for the Early Food Safety Evaluation of New Non-
Pesticidal 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.
In the Federal Register of November 24, 2004 (69 FR 68381), FDA
published a notice of availability with a 60-day comment period
requesting public comment on the collection of information in FDA's
draft guidance document titled, ``Guidance for Industry:
Recommendations for the Early Food Safety Evaluation of New Non-
Pesticidal Proteins Produced by New Plant Varieties Intended for Food
Use.''
Nonresponsive comments
FDA received approximately 5,000 letters in response to the
November 24, 2004, notice. However, many of these letters contained
comments that were not responsive to the PRA questions. For example,
several comments expressed the following opinions: The collection of
information was insufficient to ensure safety; the agency might not be
able to commit sufficient resources to performing early food safety
reviews without having to redirect resources from other tasks; the
decision should not be left to the developer regarding when to submit
an early food safety evaluation to the agency; and the objectivity and
scientific expertise of the individuals reviewing the information may
be inadequate.
(Response) These comments are general comments directed to the
adequacy of the guidance, rather than specific comments relevant to the
collection of information; therefore, these non-responsive comments
will not be addressed in this document.
Responsive comments
FDA received several letters with specific comments responsive to
the comment request concerning the proposed information collection in
the notice. The comments and FDA's responses follow.
(Comment 1) Several comments were supportive of the information
collection, stating that the information collection was necessary for
FDA to fulfill statutory requirements to protect the safety of the food
supply. Relevant to the minimization of burden, several of these
comments also noted that the information collection was appropriately
limited in scope to prevent duplicative submissions among Federal
agencies.
(Response) These comments provide support for the utility of the
information collection and confirm that the collection will not result
in a duplicative information collection among Federal agencies.
(Comment 2) One comment suggested that FDA should minimize the
burden on developers by referencing in the guidance the availability of
public protein databases that could be useful in the evaluation of
allergen or toxin homology.
(Response) FDA does not want to reference or list the various
databases because to do so would imply that FDA is endorsing any or all
of them. FDA finds that there are several databases in the public
domain that are easily obtained through the internet, are known in the
scientific community, and are in common use by developers of
bioengineered crops.
(Comment 3) One comment suggested that FDA could minimize the
burden of the proposed collection of information by clarifying that a
weight of the evidence approach is applied to the assessment of
potential allergenicity of a new protein. The comment further suggested
that alternative methods and protocols be considered in the evaluation
of the allergenicity of new proteins.
(Response) FDA's guidance does not state that a weight of the
evidence approach will be applied to the evaluation. The guidance
describes a case-by-case evaluation that recognizes that different
pieces of information may have varying importance for the food safety
evaluation depending on the characteristics of the protein. As stated
in the guidance, developers are free to use alternative approaches in
their evaluations. The comment fails to explain how a weight of the
evidence approach would reduce the burden under the PRA.
(Comment 4) One comment suggested as an approach to minimize burden
on developers that FDA treat highly similar proteins as a family of
proteins, if they differ only by a few amino acids but retain the same
function, rather than evaluating each protein individually, though the
comment further suggests that certain aspects of a protein may be
evaluated individually.
(Response) FDA notes that the guidance is intended to consider
specific proteins, not protein families. FDA further notes that even
small changes in amino acid sequence may alter a protein, and these
small differences could also have implications for food safety.
However, if there is relevant information contained in a previous
submission, that information can be incorporated by reference into a
current submission for a new protein evaluation.
(Comment 5) One comment suggested as a means of minimizing burden
of the proposed collection of information that
[[Page 7050]]
FDA provide standard forms or formats for certain elements of the
submission (e.g., bioinformatics reports). The comment also suggested
minimizing burden by making greater use of electronic submissions.
(Response) FDA has considered the use of standardized forms or
formats and at this time does not believe that their use would reduce
the burden of the information collection. The use of standardized forms
could discourage alternative approaches for the presentation of data in
an evaluation that might more clearly or thoroughly set forth the data.
Developers will have access to the forms and formats used by previous
submitters and are free to use them; thus, at this time we do not
perceive a need for a standardized form. Based on its experience in
evaluation of submissions FDA will in the future revisit whether the
use of standardized forms and formats would be advantageous to
developers.
With respect to electronic submissions, FDA states in the guidance
that electronic submissions are acceptable, but one paper copy is also
requested. Efforts are underway at FDA to convert in the future to a
submission process that is entirely electronic.
(Comment 6) One comment stated that a way to enhance the quality,
utility, and clarity of the information to be collected is to follow
guidance available from the Codex Alimentarius. Although the comment
did not specify which guidance from the Codex Alimentarius FDA should
follow, FDA believes that the comment is referring to the Codex
Alimentarius ``Guideline for the Conduct of Food Safety Assessment of
Foods Derived from Recombinant-DNA Plants'' (CAC/GL 45-2003) (the Codex
Plant Guideline), containing ``Annex: Assessment of Possible
Allergenicity'' (the Codex Allergenicity Annex). The comment also
stated that FDA should make Codex guidance a mandatory part of its
guidance.
(Response) FDA agrees in part and disagrees in part. FDA notes that
its recommendations in this guidance are consistent with the approach
recommended in the Codex Plant Guideline. In fact, FDA references the
Codex Plant Guideline as a resource to be consulted by a developer in
evaluating the food safety of a new protein. However, FDA notes that
the Codex Plant Guideline addresses a broad range of issues associated
with food safety assessment of food derived from bioengineered plants.
While FDA's guidance is consistent with the Codex Plant Guideline, it
does not address the entire broad range of issues as that document.
FDA's guidance is focused on the food safety issues that might arise
from the intermittent, low-level presence of material from a plant
being developed for food and feed use. FDA believes that any potential
risk from the intermittent, low level presence of such material in the
food supply would be limited to the food safety of the new proteins.
FDA references the Codex Plant Guideline, paragraphs 34-43 under
Expressed Substances (non-nucleic acid substances) and the Codex
Allergenicity Annex, for that component of the safety review.
FDA disagrees with the comment's suggestion that the agency make
the Codex Plant Guideline a mandatory part of its guidance. While FDA
believes that the Codex Plant Guideline and the Codex Allergenicity
Annex are useful documents, it recognizes that other approaches may
also be appropriate.
(Comment 7) One comment stated that while the information to be
collected is essential and important for FDA to obtain, the information
is inadequate to fulfill FDA's ``stated and mandated goals,'' and
therefore it is of questionable utility.
(Response) FDA disagrees. The guidance is properly focused on the
food safety assessment of a new protein produced in a new plant variety
when there might be a low level, intermittent presence of material from
a plant being developed for food. Although the commenter would like
more information to be presented for FDA review at this stage, FDA
notes that more information is not necessary because the information
that the guidance recommends a developer collect and present to FDA as
part of a food safety evaluation of a protein is adequate for the
specific assessment that FDA is making at this stage. FDA recommends
that a broader scope of information be presented to FDA for review at
subsequent evaluation stages. For example, when a developer utilizes
the recommendations articulated in FDA's guidance entitled,
``Consultation Procedures for New Plant Varieties'' (available at
http://frwebgate.access.gpo.gov/cgi-bin/leaving.cgi?from=leavingFR.html&log=linklog&to=http://www.cfsan.fda.gov/~lrd/consulpr.html), FDA expects that
significantly more information will be presented during the
consultation.
(Comment 8) Several comments challenged the accuracy of FDA's
estimate of the burden of the proposed collection of information. These
comments opined that FDA should collect more extensive information than
what is proposed in the guidance, and they concluded, therefore, that
FDA had underestimated the burden of the proposed information
collection. The comments did not challenge the accuracy of the burden
estimate for the information as proposed in the guidance.
(Response) FDA notes that the comments did not challenge the
accuracy of FDA's estimate, rather they challenged what FDA recommends
in the guidance. FDA believes that the estimate of the burden of the
proposed collection of information is accurate.
FDA estimates the burden of this collection of information as
follows:
Table 1.--Estimated Annual Reporting Burden\1\
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Annual Frequency per Total Annual
No. of Respondents Response Responses Hours Per Response Total Hours
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First four data components 20 1 20 4 80
Two other data components 20 1 20 16 320
Total ......................... ......................... .................... .................... 400
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\1\There are no capital costs or operating and maintenance costs associated with this collection of information.
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. Many
developers of novel plants may choose not to submit an evaluation
because the field testing of a plant containing a new protein is
conducted
[[Page 7051]]
in such a way (e.g., on such a small scale, or in such isolated
conditions, etc.) that cross-pollination with traditional crops or
commingling of plant material is not likely to be an issue. Also, other
developers may have previously communicated with FDA about the food
safety of a new plant protein, for example, when the same protein was
expressed in a different crop.
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 food made from a new bioengineered
plant variety; it is usually bioengineered varieties of plants that are
the subject of a consultation with FDA.
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).
In Table 1 of this document, row 2 shows that for 20 evaluations, the
total burden for these two data components is 320 hours.
Dated: February 6, 2006.
Jeffrey Shuren,
Assistant Commissioner for Policy.
[FR Doc. E6-1806 Filed 2-9-06; 8:45 am]
BILLING CODE 4160-01-S