[Federal Register Volume 88, Number 141 (Tuesday, July 25, 2023)]
[Notices]
[Pages 47886-47888]
[FR Doc No: 2023-15645]

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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket Nos. FDA-2022-D-0055 and FDA-2020-N-1790]

M7(R2) Assessment and Control of Deoxyribonucleic Acid Reactive
(Mutagenic) Impurities in Pharmaceuticals To Limit Potential
Carcinogenic Risk, M7(R2) Addendum, and M7(R2) Questions and Answers;
International Council for Harmonisation; Guidances for Industry;
Availability

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice of availability.

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SUMMARY: The Food and Drug Administration (FDA or Agency) is announcing
the availability of a final guidance for industry entitled ``M7(R2)
Assessment and Control of DNA Reactive (Mutagenic) Impurities in
Pharmaceuticals to Limit Potential Carcinogenic Risk'' (M7(R2)
Guidance) and two supplemental documents entitled ``M7(R2) Addendum:
Application of the Principles of the ICH M7 Guidance to Calculation of
Compound-Specific Acceptable Intakes'' (M7(R2) Addendum) and ``M7(R2)
Assessment and Control of DNA Reactive (Mutagenic) Impurities in
Pharmaceuticals to Limit Potential Carcinogenic Risk Questions and
Answers'' (M7(R2) Questions and Answers). The M7(R2) Guidance, M7(R2)
Addendum, and M7(R2) Questions and Answers were prepared under the
auspices of the International Council for Harmonisation of Technical
Requirements for Pharmaceuticals for Human Use (ICH). The guidance and
supplemental documents are intended to harmonize the considerations for
assessment and control of DNA reactive (mutagenic) impurities. The
M7(R2) Guidance and M7(R2) Addendum replace the guidance for industry
entitled ``M7(R1) Assessment and Control of DNA Reactive (Mutagenic)
Impurities in Pharmaceuticals To Limit Potential Carcinogenic Risk,''
issued on March 14, 2018. The M7(R2) Guidance, M7(R2) Addendum, and
M7(R2) Questions and Answers, also finalize the draft guidances for
industry entitled ``M7(R2) Addendum: Application of the Principles of
the ICH M7 Guideline to Calculation of Compound-Specific Acceptable
Intakes'' and ``M7 Assessment and Control of DNA Reactive (Mutagenic)
Impurities in Pharmaceuticals To Limit Potential Carcinogenic Risk--
Questions and Answers'' issued on April 7, 2022, and September 29,
2020, respectively.

DATES: The announcement of the guidance is published in the Federal
Register on July 25, 2023.

ADDRESSES: You may submit either electronic or written comments on
Agency guidances at any time as follows:

Electronic Submissions

    Submit electronic comments in the following way:
     Federal eRulemaking Portal: https://www.regulations.gov.
Follow the instructions for submitting comments. Comments submitted
electronically, including attachments, to https://www.regulations.gov
will be posted to the docket unchanged. Because your comment will be
made public, you are solely responsible for ensuring that your comment
does not include any confidential information that you or a third party
may not wish to be posted, such as medical information, your or anyone
else's Social Security number, or confidential business information,
such as a manufacturing process. Please note that if you include your
name, contact information, or other information that identifies you in
the body of your comments, that information will be posted on https://www.regulations.gov.
     If you want to submit a comment with confidential
information that you do not wish to be made available to the public,
submit the comment as a written/paper submission and in the manner
detailed (see ``Written/Paper Submissions'' and ``Instructions'').

Written/Paper Submissions

    Submit written/paper submissions as follows:
     Mail/Hand Delivery/Courier (for written/paper
submissions): Dockets Management Staff (HFA-305), Food and Drug
Administration, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852.
     For written/paper comments submitted to the Dockets
Management Staff, FDA will post your comment, as well as any
attachments, except for information submitted, marked and identified,
as confidential, if submitted as detailed in ``Instructions.''
    Instructions: All submissions received must include the Docket No.
FDA-2022-D-0055 for ``M7(R2) Assessment and Control of DNA Reactive
(Mutagenic) Impurities in Pharmaceuticals to Limit Potential
Carcinogenic Risk,'' and ``M7(R2) Addendum: Application of the
Principles of the ICH M7 Guidance to Calculation of Compound-Specific
Acceptable Intakes,'' or Docket No. FDA-2020-N-1790 for ``M7(R2)
Assessment and Control of DNA Reactive (Mutagenic) Impurities in
Pharmaceuticals to Limit Potential Carcinogenic Risk Questions and
Answers.'' Received comments will be placed in the docket and, except
for those submitted as ``Confidential Submissions,'' publicly viewable
at https://www.regulations.gov or at the Dockets Management Staff
between 9 a.m. and 4 p.m., Monday through Friday,<PHONE_NUMBER>.
     Confidential Submissions--To submit a comment with
confidential information that you do not wish to be made publicly
available, submit your comments only as a written/paper submission. You
should submit two copies total. One copy will include the information
you claim to be confidential with a heading or cover note that states
``THIS DOCUMENT CONTAINS CONFIDENTIAL INFORMATION.'' The Agency will
review this copy, including the claimed confidential information, in
its consideration of comments. The second copy, which will have the
claimed confidential information redacted/blacked out, will be
available for public viewing and posted on https://www.regulations.gov.
Submit both copies to the Dockets Management Staff. If you do not wish
your name and contact information to be made publicly available, you
can provide this information on the cover sheet and not in the body of
your comments and you must identify this information as
``confidential.'' Any information marked as ``confidential'' will not
be disclosed except in accordance with 21 CFR 10.20 and other
applicable disclosure law. For more information about FDA's posting of
comments to public dockets, see 80 FR 56469, September 18, 2015, or
access the information at: https://www.govinfo.gov/content/pkg/FR-2015-09-18/pdf/2015-23389.pdf.
    Docket: For access to the docket to read background documents or
the electronic and written/paper comments received, go to https://www.regulations.gov and insert the docket number, found in brackets in
the heading of this document, into the ``Search'' box and follow the
prompts and/or go to the Dockets Management Staff, 5630 Fishers Lane,
Rm. 1061, Rockville, MD 20852,<PHONE_NUMBER>.
    You may submit comments on any guidance at any time (see 21 CFR
10.115(g)(5)).
    Submit written requests for single copies of this guidance to the
Division of Drug Information, Center for Drug Evaluation and Research,
Food and Drug Administration, 10001 New Hampshire Ave., Hillandale
Building, 4th Floor, Silver Spring, MD 20993-0002, or the Office of
Communication, Outreach and Development, Center for Biologics
Evaluation and Research (CBER), Food and Drug Administration, 10903 New
Hampshire Ave., Bldg. 71, Rm. 3128, Silver Spring, MD 20993-0002. Send
one self-addressed adhesive label to assist that office in processing
your requests. The guidance may also be obtained by mail by calling
CBER at 1-800-835-4709 or<PHONE_NUMBER>. See the SUPPLEMENTARY
INFORMATION section for electronic access to the guidance document.

FOR FURTHER INFORMATION CONTACT:
    Regarding the guidance: Aisar Atrakchi, Center for Drug Evaluation
and Research, Food and Drug

Administration, 10904 New Hampshire Ave., Bldg. 22, Rm. 4118, Silver
Spring, MD 20993-0003,<PHONE_NUMBER>.
    Regarding the ICH: Jill Adleberg, Center for Drug Evaluation and
Research, Food and Drug Administration, 10903 New Hampshire Ave., Bldg.
51, Rm. 6364, Silver Spring, MD 20993-0002,<PHONE_NUMBER>,
[email protected].

SUPPLEMENTARY INFORMATION:

I. Background

    FDA is announcing the availability of a guidance for industry
entitled ``M7(R2) Assessment and Control of DNA Reactive (Mutagenic)
Impurities in Pharmaceuticals to Limit Potential Carcinogenic Risk.''
The guidance was prepared under the auspices of ICH. ICH seeks to
achieve greater regulatory harmonization worldwide to ensure that safe,
effective, high-quality medicines are developed, registered, and
maintained in the most resource-efficient manner.
    By harmonizing the regulatory requirements in regions around the
world, ICH guidelines enhance global drug development, improve
manufacturing standards, and increase the availability of medications.
For example, ICH guidelines have substantially reduced duplicative
clinical studies, prevented unnecessary animal studies, standardized
the reporting of important safety information, and standardized
marketing application submissions.
    The six Founding Members of the ICH are FDA; the Pharmaceutical
Research and Manufacturers of America; the European Commission; the
European Federation of Pharmaceutical Industries Associations; the
Japanese Ministry of Health, Labour, and Welfare; and the Japanese
Pharmaceutical Manufacturers Association. The Standing Members of the
ICH Association include Health Canada and Swissmedic. ICH membership
continues to expand to include other regulatory authorities and
industry associations from around the world (refer to https://www.ich.org/).
    ICH works by engaging global regulatory and industry experts in a
detailed, science-based, and consensus-driven process that results in
the development of ICH guidelines. The regulators around the world are
committed to consistently adopting these consensus-based guidelines,
realizing the benefits for patients and for industry.
    As a Founding Regulatory Member of ICH, FDA plays a major role in
the development of each of the ICH guidelines, which FDA then adopts
and issues as guidance for industry. FDA's guidance documents do not
establish legally enforceable responsibilities. Instead, they describe
the Agency's current thinking on a topic and should be viewed only as
recommendations, unless specific regulatory or statutory requirements
are cited.
    In the Federal Register of April 7, 2022 (87 FR 20435), FDA
published a notice announcing the availability of a draft guidance for
industry entitled ``M7(R2) Addendum: Application of the Principles of
the ICH M7 Guideline to Calculation of Compound-Specific Acceptable
Intakes,'' which included ICH assembly approved changes, including the
separation of the main guidance and addendum into two separate
documents. In the Federal Register of September 29, 2020 (85 FR 61009),
FDA published a notice announcing the availability of a draft guidance
for industry entitled ``M7 Assessment and Control of DNA reactive
(Mutagenic) Impurities in Pharmaceuticals To Limit Potential
Carcinogenic Risk--Questions and Answers.'' The notices gave interested
persons an opportunity to submit comments by May 9, 2022, and December
28, 2020, respectively.
    After consideration of the comments received and revisions to the
guidances, final drafts of the guidance and supplemental documents were
submitted to the ICH Assembly and endorsed by the regulatory Agencies
on May 24, 2022, and April 3, 2023.
    These guidances finalize the above draft guidances issued on April
7, 2022, and September 29, 2020, with no significant changes. The
M7(R2) Guidance is intended to be read in conjunction with two
accompaniment documents, the M7(R2) Addendum and the M7(R2) Questions
and Answers. The core M7(R2) Guidance includes information on mutagenic
impurities and changes to HIV treatment duration. The M7(R2) Addendum
contains monographs for mutagenic chemicals that are common in
pharmaceutical manufacturing or are useful to illustrate the principles
for deriving compound-specific intakes described in the core guidance.
The M7(R2) Questions and Answers facilitate consistent implementation
by clarifying issues and concerns identified since the first version of
the final guidance for industry, ``M7 Assessment and Control of DNA
Reactive (Mutagenic) Impurities in Pharmaceuticals to Limit Potential
Carcinogenic Risk,'' published in 2014.
    This guidance is being issued consistent with FDA's good guidance
practices regulation (21 CFR 10.115). The guidance represents the
current thinking of FDA on ``M7(R2) Assessment and Control of DNA
Reactive (Mutagenic) Impurities in Pharmaceuticals to Limit Potential
Carcinogenic Risk.'' It does not establish any rights for any person
and is not binding on FDA or the public. You can use an alternative
approach if it satisfies the requirements of the applicable statutes
and regulations.

II. Paperwork Reduction Act of 1995

    While these guidances contains no collection of information, they
do refer to previously approved FDA collections of information.
Therefore, clearance by the Office of Management and Budget (OMB) under
the Paperwork Reduction Act of 1995 (PRA) (44 U.S.C. 3501-3521) is not
required for these guidances. The previously approved collections of
information are subject to review by OMB under the PRA. The collections
of information in 21 CFR part 601 have been approved under OMB control
number 0910-0338. The collections of information pertaining to 21 CFR
parts 312 and 314 have been approved under OMB control numbers 0910-
0014 and 0910-0001, respectively. The collections of information in 21
CFR parts 210 and 211 pertaining to current good manufacturing practice
requirements have been approved under OMB control number 0910-0139.

III. Electronic Access

    Persons with access to the internet may obtain the guidance at
https://www.regulations.gov, https://www.fda.gov/drugs/guidance-compliance-regulatory-information/guidances-drugs, https://www.fda.gov/vaccines-blood-biologics/guidance-compliance-regulatory-information-biologics/biologics-guidances, or https://www.fda.gov/regulatory-information/search-fda-guidance-documents.

    Dated: July 19, 2023.
Lauren K. Roth,
Associate Commissioner for Policy.
[FR Doc. 2023-15645 Filed 7-24-23; 8:45 am]
BILLING CODE 4164-01-P


CAIR? STATE FACILITY_ NAME ORIS UNITID U n i q u e Online Year non CAIR ND Leland Olds 2817 2 Le 1975 non CAIR AR White Bluff 6009 2 W 1981 non CAIR NV Mohave 2341 2 M 1971 non CAIR NV Mohave 2341 1 M 1971 non CAIR ND Milton R Young 2823 B1 M 1970 non CAIR AR White Bluff 6009 1 W 1980 non CAIR NJ Hudson 2403 2 H 1968 non CAIR KS Jeffrey Energy Center 6068 1 Je 1978 non CAIR KS La Cygne 1241 2 La 1977 non CAIR NH Merrimack 2364 2 M 1968 non CAIR KS Jeffrey Energy Center 6068 2 Je 1980 non CAIR NE Gerald Gentleman Station 6077 2 G 1982 non CAIR OK Northeastern 2963 3314 N 1980 non CAIR ND Coal Creek 6030 1 C 1979 non CAIR NE Nebraska City 6096 1 N 1979 non CAIR NE Gerald Gentleman Station 6077 1 G 1979 non CAIR ND Leland Olds 2817 1 Le 1966 non CAIR MA Brayton Point 1619 3 Br 1969 non CAIR UT Huntington 8069 2 H 1974 non CAIR SD Big Stone 6098 1 Bi 1975 non CAIR OK Northeastern 2963 3313 N 1979 non CAIR CO Pawnee 6248 1 Pa 1981 non CAIR OR Boardman 6106 1SG Bo 1980 non CAIR NJ B L England 2378 1 B 1962 non CAIR AR Independence 6641 1 In 1983 non CAIR ND Coal Creek 6030 2 C 1981 non CAIR OK Sooner 6095 1 So 1979 non CAIR AR Flint Creek 6138 1 Fl 1978 non CAIR ND Milton R Young 2823 B2 M 1977 non CAIR OK Muskogee 2952 4 M 1977 non CAIR NM Four Corners 2442 5 Fo 1970 non CAIR AZ Cholla 113 3 C 1980 non CAIR WY Naughton 4162 2 N 1968 non CAIR CO Comanche ( 470) 470 2 C 1975 non CAIR OK Sooner 6095 2 So 1980 non CAIR WY Dave Johnston 4158 BW43 D 1964 non CAIR OK Muskogee 2952 5 M 1978 non CAIR DE Indian River 594 4 In 1980 non CAIR DE Indian River 594 3 In 1970 non CAIR KS Nearman Creek 6064 N1 N 1981 non CAIR ND Stanton 2824 1 St 1967 non CAIR WY Wyodak 6101 BW91 W 1978 non CAIR AZ Cholla 113 4 C 1981 non CAIR AZ Coronado Generating Station 6177 U2B C 1980 non CAIR NV North Valmy 8224 1 N 1981 non CAIR WY Jim Bridger 8066 BW71 Ji 1974 non CAIR MA Brayton Point 1619 1 Br 1963 non CAIR AZ Coronado Generating Station 6177 U1B C 1979 non CAIR WY Naughton 4162 1 N 1963 non CAIR WY Jim Bridger 8066 BW72 Ji 1975 non CAIR KS La Cygne 1241 1 La 1973 non CAIR MA Brayton Point 1619 2 Br 1964 non CAIR NM Four Corners 2442 4 Fo 1969 non CAIR WY Jim Bridger 8066 BW73 Ji 1976 non CAIR NM San Juan 2451 4 Sa 1982 non CAIR WY Naughton 4162 3 N 1971 non CAIR DE Edge Moor 593 4 Ed 1966 non CAIR NE North Omaha 2291 5 N 1968 non CAIR CO Comanche ( 470) 470 1 C 1973 non CAIR MT Colstrip 6076 1 C 1975 non CAIR CO Ray D Nixon 8219 1 R 1980 non CAIR MT Colstrip 6076 2 C 1976 non CAIR NM San Juan 2451 3 Sa 1979 non CAIR WY Laramie River 6204 3 La 1982 non CAIR WA Centralia 3845 BW21 C 1972 non CAIR WY Dave Johnston 4158 BW44 D 1972 non CAIR WY Laramie River 6204 1 La 1980 non CAIR WY Laramie River 6204 2 La 1981 non CAIR CO Martin Drake 492 7 M 1974 non CAIR MT J E Corette 2187 2 J 1968 non CAIR NE North Omaha 2291 4 N 1963 non CAIR AZ Irvington 126 4 Irv 1967 non CAIR WY Jim Bridger 8066 BW74 Ji 1979 non CAIR KS Tecumseh Energy Center 1252 10 Te 1962 non CAIR NM San Juan 2451 2 Sa 1973 non CAIR CT Bridgeport Harbor Station 568 BHB3 Br 1968 non CAIR ND R M Heskett 2790 B2 R 1963 non CAIR KS Quindaro 1295 2 Q 1971 non CAIR WA Centralia 3845 BW22 C 1973 non CAIR NM San Juan 2451 1 Sa 1976 non CAIR CO Martin Drake 492 6 M 1968 non CAIR UT Hunter ( Emery) 6165 2 H 1980 non CAIR UT Huntington 8069 1 H 1977 non CAIR UT Hunter ( Emery) 6165 1 H 1978 non CAIR NE Sheldon 2277 1 Sh 1968 non CAIR KS Quindaro 1295 1 Q 1965 non CAIR NM Four Corners 2442 3 Fo 1964 non CAIR KS Lawrence Energy Center 1250 5 La 1971 non CAIR CO Craig 6021 C2 C 1979 non CAIR CO Cherokee 469 4 C 1968 non CAIR AZ Navajo Generating Station 4941 3 N 1976 non CAIR AZ Apache Station 160 2 Ap 1979 non CAIR CO Martin Drake 492 5 M 1962 non CAIR NM Four Corners 2442 1 Fo 1963 non CAIR AZ Apache Station 160 3 Ap 1979 non CAIR CO Hayden 525 H2 H 1976 non CAIR AZ Navajo Generating Station 4941 1 N 1974 non CAIR NM Four Corners 2442 2 Fo 1963 non CAIR CO Hayden 525 H1 H 1965 non CAIR NE Lon D Wright Power Plant 2240 8 Lo 1976 non CAIR NJ B L England 2378 2 B 1964 non CAIR AZ Navajo Generating Station 4941 2 N 1975 non CAIR AZ Cholla 113 2 C 1978 non CAIR CO Valmont 477 5 Va 1964 non CAIR CO Craig 6021 C1 C 1980 non CAIR CO Cherokee 469 3 C 1962 non CAIR NV Reid Gardner 2324 2 R 1968 non CAIR NV Reid Gardner 2324 3 R 1976 non CAIR NV Reid Gardner 2324 1 R 1965 Nameplate Capacity ( of generator connected to boiler) 2004 NOX TONS 2004 SO2 TONS 2004 SO2 controls $/ Ton $/ Ton with allowance savings 440.00 10,379 32,990 Projected # N/ A # N/ A 850.00 9,011 22,979 0 1,597 1,297 818.10 10,046 21,967 0 2,701 2,401 818.10 10,822 21,613 0 2,703 2,403 257.00 9,785 21,586 Projected # N/ A # N/ A 850.00 9,196 21,519 0 1,605 1,305 659.70 8,061 21,467 0 1,693 1,393 720.00 9,413 20,965 WLS # N/ A # N/ A 685.17 10,287 20,694 O # N/ A # N/ A 345.60 3,069 20,582 Projected # N/ A # N/ A 720.00 8,301 20,561 WLS # N/ A # N/ A 681.30 9,960 16,582 0 1,374 1,074 472.50 7,048 15,889 0 1,180 880 506.01 5,552 15,742 WL # N/ A # N/ A 615.87 9,348 15,593 0 1,333 1,033 681.30 11,747 15,453 0 1,346 1,046 216.00 2,510 15,448 0 1,247 947 642.60 6,019 15,218 Projected # N/ A # N/ A 446.40 5,645 14,381 0 961 661 456.00 17,032 14,293 0 1,511 1,211 472.50 6,007 13,942 0 877 577 500.00 4,515 12,550 0 1,089 789 560.50 7,834 12,390 0 1,655 1,355 136.00 2,199 12,092 0 1,281 981 850.00 7,560 11,761 0 1,603 1,303 506.01 5,391 11,469 WL # N/ A # N/ A 568.80 7,632 10,189 0 1,751 1,451 558.00 4,945 10,099 0 1,599 1,299 477.00 13,815 9,795 DA # N/ A # N/ A 572.40 5,773 9,704 0 1,697 1,397 818.10 13,947 9,607 WL # N/ A # N/ A 288.90 3,319 8,928 0 1,441 1,141 217.60 4,813 8,832 0 1,289 989 350.00 4,241 8,582 0 1,809 1,509 568.80 5,754 8,573 0 1,790 1,490 229.50 4,931 8,433 0 1,475 1,175 572.40 5,835 8,386 0 1,690 1,390 442.40 3,037 8,155 0 899 599 176.80 1,498 8,060 0 1,492 1,192 261.00 4,316 8,024 0 1,258 958 172.00 2,121 7,869 0 1,299 999 362.07 4,952 7,862 DL # N/ A # N/ A 414.00 4,357 7,650 WL # N/ A # N/ A 410.94 7,270 7,214 WLS # N/ A # N/ A 254.26 3,538 7,196 0 2,213 1,913 560.60 9,635 6,875 SB # N/ A # N/ A 241.02 1,753 6,833 Projected # N/ A # N/ A 410.94 6,109 6,731 WLS # N/ A # N/ A 163.20 3,861 6,618 0 1,578 1,278 560.60 9,668 6,616 SB # N/ A # N/ A 893.40 28,891 6,495 WLS # N/ A # N/ A 241.00 1,611 6,448 Projected # N/ A # N/ A 818.10 9,997 6,197 WL # N/ A # N/ A 560.60 9,970 6,039 SB # N/ A # N/ A 534.00 8,445 5,940 WLS # N/ A # N/ A 326.40 5,603 5,723 SB # N/ A # N/ A 176.80 1,399 5,665 0 1,038 738 217.60 2,158 5,476 0 2,076 1,776 350.00 3,420 5,368 0 1,853 1,553 358.40 5,321 5,057 WL # N/ A # N/ A 207.00 2,514 4,964 0 2,518 2,218 358.40 5,848 4,933 WL # N/ A # N/ A 534.00 7,330 4,811 WLS # N/ A # N/ A 570.00 7,424 4,456 WL # N/ A # N/ A 729.99 8,305 4,429 WLS # N/ A # N/ A 360.00 5,417 4,310 O # N/ A # N/ A 570.00 6,457 4,178 WLS # N/ A # N/ A 570.00 5,617 3,833 WLS # N/ A # N/ A 132.00 1,835 3,773 0 2,063 1,763 191.00 2,067 3,584 0 2,950 2,650 136.00 1,276 3,314 0 2,650 2,350 173.30 1,765 3,296 0 1,981 1,681 560.60 7,844 3,264 SB # N/ A # N/ A 176.00 1,612 3,174 0 2,131 1,831 350.00 5,912 2,980 WLS # N/ A # N/ A 399.50 2,160 2,790 Projected # N/ A # N/ A 75.00 945 2,754 0 2,480 2,180 157.50 878 2,475 0 2,095 1,795 729.99 7,135 2,455 WLS # N/ A # N/ A 361.00 5,194 2,448 WLS # N/ A # N/ A 75.00 1,252 2,445 0 2,587 2,287 446.40 6,238 2,402 WL # N/ A # N/ A 446.40 5,025 2,346 WL # N/ A # N/ A 446.40 5,882 2,338 WL # N/ A # N/ A 108.80 4,080 2,311 0 3,277 2,977 81.60 2,209 2,310 0 3,310 3,010 253.44 6,308 2,223 WL # N/ A # N/ A 458.00 3,255 2,003 WLS # N/ A # N/ A 446.40 5,551 1,787 WLS # N/ A # N/ A 350.00 4,268 1,679 SB # N/ A # N/ A 803.16 10,679 1,615 WLS # N/ A # N/ A 194.70 4,266 1,525 WL # N/ A # N/ A 50.00 797 1,460 0 2,580 2,280 190.08 6,044 1,399 WL # N/ A # N/ A 194.70 3,305 1,395 WL # N/ A # N/ A 275.40 3,653 1,391 DL # N/ A # N/ A 803.16 12,606 1,346 WLS # N/ A # N/ A 190.08 4,447 1,345 WL # N/ A # N/ A 190.00 4,057 1,225 DL # N/ A # N/ A 91.50 499 1,181 0 4,243 3,943 163.20 1,881 1,068 WLS # N/ A # N/ A 803.16 10,701 958 WLS # N/ A # N/ A 288.90 3,288 951 WL # N/ A # N/ A 166.25 2,431 826 DL # N/ A # N/ A 446.40 5,478 768 WLS # N/ A # N/ A 150.00 1,838 664 DL 4,461 4,161 114.00 2,286 269 SB # N/ A # N/ A 114.00 1,672 235 SB # N/ A # N/ A 114.00 1,771 215 SB # N/ A # N/ A # N/ A # N/ A # N/ A # N/ A # N/ A # N/ A # N/ A # N/ A # N/ A # N/ A # N/ A # N/ A # N/ A # N/ A # N/ A # N/ A # N/ A # N/ A # N/ A # N/ A # N/ A # N/ A # N/ A # N/ A # N/ A # N/ A # N/ A # N/ A # N/ A # N/ A # N/ A # N/ A # N/ A # N/ A # N/ A # N/ A # N/ A # N/ A # N/ A # N/ A # N/ A # N/ A # N/ A # N/ A # N/ A # N/ A # N/ A # N/ A # N/ A # N/ A # N/ A # N/ A # N/ A # N/ A # N/ A # N/ A # N/ A # N/ A # N/ A # N/ A 4160.547363 3943.328086 3010.101383 2976.858513 2650.429857 2402.709712 2401.322191 2350.215614 2286.887321 2279.534494 2218.234673 2179.600285 1913.299158 1830.620991 1795.477331 1776.247722 1763.032811 1680.53876 1553.498741 1508.547473 1490.112276 1450.803695 1396.722974 1392.896186 1390.13429 1354.634707 1305.150995 1303.059645 1298.906108 1296.52808 1277.795483 1210.953059 1191.579505 1175.430292 1141.104032 1074.298034 1046.417004 1033.437727 999.3754568 988.6263272 980.9057043 957.6268257 946.5355715 879.6926721 788.9493005 738.0016156 661.2641262 598.9371595 576.6549224


Bruce Lanphear<EMAIL_ADDRESS> 01/10/2007 05:02 PM

To

Richard Hornung<EMAIL_ADDRESS>David Svendsgaard/RTP/USEPA/US@EPA

cc

Subject

Re: Fw: Question about the Lanphear et al., 2005

David:

Please find a revised Table 4 attached.  Please share this with Zach

and your other colleagues at US EPA.

Bruce


TER-CX1 Insecticide and Ovicide Concentrate

Controls, Manages and Prevents Bed Bug Infestations,

 Kills Bed Bug Adults, Nymphs and Their Eggs

Active Ingredient:

           Cold Pressed Neem Oil	22.0%

Other
Ingredients.............................................................
........ 78.0%

Total
                   	100.0%

KEEP OUT OF REACH OF CHILDREN

CAUTION

READ ALL DIRECTIONS BEFORE USING THIS PRODUCT

If you do not understand the label, find someone to explain it to you in
detail.

(Si usted no entiende la etiqueta, busque a alguien para que se la
explique a usted en detalle.)

EPA Reg. No. 88760–E

EPA Est. No. XXXXX-A	NET CONTENTS:  3, 16, 32 or 64 oz.,

1 or 5 Gallons

Manufactured by:

Terramera, Inc.

131-887 Great Northern Way

Vancouver, BC, Canada V5T 4T5

PRECAUTIONARY STATEMENTS

HAZARDS TO HUMANS AND DOMESTIC ANIMALS

Caution:  Harmful if swallowed. Wash thoroughly with soap and water
after handling and before eating, drinking, chewing gum, using tobacco
or using the toilet.

Route of Entry	First Aid

If swallowed 	Call a poison control center or doctor immediately for
treatment advice.

Have person sip a glass of water if able to swallow.

Do not induce vomiting unless told to by a poison control center or
doctor.

Do not give anything to an unconscious person.

Have the product container or label with you when calling a poison
control center, doctor, or going for treatment. For emergency
information concerning this product, call the National Pesticides
Information Center (NPIC) at 1-800-858-7378 seven days a week, 6:30 am
to 4:30 pm Pacific Time (NPIC Web site: www.npic.orst.edu)

DIRECTIONS FOR USE

It is a violation of Federal Law to use this product in a manner
inconsistent with its labeling.

Read entire label.  Use strictly in accordance with precautionary
statements and directions, and with applicable state and Federal
regulations.

General Information

TER-CX1 Insecticide and Ovicide is a concentrated liquid insecticide and
ovicide for indoor use containing 22% pure cold pressed neem oil, and
requires dilution prior to use.

TER-CX1 Insecticide and Ovicide provides effective knockdown, residual
and preventative control of bed bugs, including pyrethroid-resistant bed
bugs, and their eggs. TER-CX1 Insecticide and Ovicide kills bed bugs and
eggs using a unique mode of action, and helps manage the spread of
pesticide resistance.

Use TER-CX1 Insecticide and Ovicide to control bed bugs and cellar
spiders.

For Bed Bug Control:

TER-CX1 Insecticide and Ovicide is an emulsifiable concentrate. Dilute
product with water prior to use according to the Mixing Instructions.  A
low-pressure directed or broadcast sprayer, or similar equipment, may be
used for uniform and even application. Spray until moist. Allow to dry
completely. For optimal performance, close doors and windows and turn
off air circulation (e.g. heaters and air conditioners) and keep site of
application undisturbed for at least 4 hours after treatment. After 4
hours, return to normal ventilation and allow reentry into treated area.

For crack and crevice applications, use a straw tip or pin tip nozzle.

Use TER-CX1 Insecticide and Ovicide on a variety of indoor surfaces,
fabrics and materials, painted and unpainted wood, under beds, box
springs, bed frames, headboards, mattresses, linens, under and behind
night stands, closets, dressers, curtains, blinds, under and behind wall
hangings, carpets, rugs, upholstery, wall and window treatments,
suitcases, seams, points where carpets and wall meet, moldings, and
anywhere bed bugs may harbor or their eggs may be found. Spraying all
surfaces, especially tufts, folds, seams, edges, cracks and crevices,
will help minimize further infestation.

TER-CX1 Insecticide and Ovicide may cause damage or discolor certain
surfaces and materials, including papers and soft plastics such as
plexiglass, plastic varnishes, some flooring and finishes, frames,
photographs, artwork, wallpaper and consumer electronics. Make small
inconspicuous spot treatments to test all surfaces and fabrics for
colorfastness, discoloration or damage before use.

Use TER-CX1 Insecticide and Ovicide in indoor areas including
residential homes, multi-dwelling units, apartments, dormitories,
hospitals, nursing homes, prisons, temporary shelters, aircraft, buses,
marine vessels, airports, offices, theaters, hotels, motels,
restaurants, lounges, arenas, retail stores, conference centers and
other indoor spaces.

For Direct Treatment:

Apply TER-CX1 Insecticide and Ovicide to kill bed bugs or eggs by
spraying directly.

For Indirect Residual Treatment:

Apply TER-CX1 Insecticide and Ovicide to surfaces and fabrics to kill or
prevent bed bug infestations for up to 2 weeks and eggs for up to 3
weeks.

Mixing Instructions:

Mix 1 part TER-CX1 Insecticide and Ovicide with 3 parts water.

To make one gallon of TER-CX1 Insecticide and Ovicide:

Fill tank with ½ gallon of water

For better results use warm water (60-85oF)

Add one quart (32 oz) of TER-CX1 Insecticide and Ovicide

Agitate to mix well

Fill tank to one gallon by adding one quart of water

Close sprayer tank and agitate well before use

Use diluted TER-CX1 Insecticide and Ovicide within the same day or
within 12 hours of dilution.

Application Rates and Treatment Schedule:

Spray until treated surfaces are moist. Use approximately one (1) gallon
diluted TER-CX1 Insecticide and Ovicide per 200-800 sq.ft. depending on
surface treated.

Allow 4 hours for product to completely dry before reentry.

For bed bug adults, nymphs and eggs, re-apply every 1 to 2 weeks or as
needed.

For bed bug eggs only, re-apply every 2 to 3 weeks or as needed.

{Optional marketing claims, may be used on any panel}

GENERAL CLAIMS:

[Controls] [Manages] [and] [Prevents] bed bug infestations [for up to
three weeks] [when used as directed]

[100%] Effective [for] [bed bug control] [up to three weeks] [when used
as directed]

Long-lasting [protection from] [bed bug][s] [control] [when used as
directed]

[The only product that] kills [bedbugs], [nymphs], [and eggs] [prevents
egg-hatch] [as a residual treatment] [when used as directed]

[Stop] [stops] [bed bug] infestations [fast] [quickly] [when used as
directed]

Patent[ed][-pending] [formula]

[Kills] [Keeps on killing] [100%] [Protects] [From] bed bug [adults]
[and] [nymphs] [for up to 2 weeks] [on treated surfaces] [and] [prevents
egg hatch] [eggs] [on contact] [and] [or] [as a residual treatment]
[for] [up to 3 weeks] [with Regular Use] [when used as directed]

[Limit][s] [prevent][s] [the] [growth] [spread] [of] bed bug[s]
[infestations] [populations] [when used as directed]

Effective against [pyrethroid] [chemical] resistant [field] strains
[when used as directed]

All-in-one [protection from] [bed bug[s]] [and egg[s]] [kill] [and]
[protection] [when used as directed]

Be Bed Bug Free

Freedom From Bed Bugs

Works quickly [when used as directed]	[Great] [for] [Use] [as] [part of]
[an] Integrated Pest Management [IPM] [strategy]

[Just] spray [and] [leave to dry] [walk away]

Can be [readily] washed out [of] [fabrics]

 [No] [Non-]staining

[Starts] work[s][ing] [immediately] [quickly] [when used as directed]

[works] [kills] within hours [and keeps] [killing] [working] [for weeks]
[when used as directed]

The only registered bio-pesticide [labeled] for [indoor] use [as] [a]
[an] [indoor] [surface], [fabric] [and] [crack and crevice] [treatment]
[product] [for] [against] bed bugs

Use on [mattresses] [beds] [upholstery] [wood] [carpets] [rugs]
[suitcases] [fabrics]

[Kills] [bed bugs] [and] [Works] [Protects] [continues] [killing]
[protecting] [working] [and] [preventing egg hatch] for weeks [after
treatment] [when used as directed]

[Providing] [Provides] [Delivers] Around the clock protection from Bed
Bugs [and their eggs] [when used as directed]

[Use] The Power of Neem

[Derived] [Developed] [Formulated] From  [cold-pressed] [natural] [tree]
[seed] [Ingredients] [Oils] [the neem tree]

[All] [Ingredients] [are] Generally Recognized as Safe [GRAS] [by the
FDA]

Broad [use] [application] [bed bug protection]

[A] [Smarter] [Safer] [Faster] way to [Control] [Manage] [Protect]
[From] Bed bugs

[The] [Bed Bug] [and][Egg] Killer

[a] [plant based] [botanical] insecticide

STORAGE AND DISPOSAL

DO NOT contaminate water, food, or feed by pesticide storage or
disposal. Open dumping is prohibited. Do not reuse container.

PESTICIDE STORAGE: Do not store this product above 104oF or below 20oF
for extended periods of time. Keep containers tightly closed when not in
use. Keep containers tightly closed and in original containers when not
in use.  Do not store exposed to ultraviolet light (sunlight) or
moisture.

PESTICIDAL DISPOSAL: Wastes resulting from the use of this product must
be disposed of on site or at an approved waste disposal facility.

CONTAINER HANDLING:  Non-refillable container.  Do not reuse or refill
this container. Triple rinse container (or equivalent) promptly after
emptying. Then offer for recycling if available or puncture and dispose
of in a sanitary landfill, or by incineration, or, if allowed by state
and local authorities, by burning.  If burned, stay out of smoke.

Triple rinse containers small enough to shake (capacity ≤ 5 gallons)
as follows:  Empty the remaining contents into application equipment or
a mix tank and drain for 10 seconds after the flow begins to drip. Fill
the container 1⁄4 full with water and recap. Shake for 10 seconds.
Pour rinsate into application equipment or a mix tank or store rinsate
for later use or disposal. Drain for 10 seconds after the flow begins to
drip. Repeat this procedure two more times.

NOTICE ON CONDITIONS OF SALE

Conditions of Sale and Warranty

IMPORTANT: READ BEFORE USE

Read the entire Directions for Use, Conditions, Disclaimer of Warranties
and Limitations of Liability before using this product. If terms are not
acceptable, return the unopened product container at once.

To the extent consistent with applicable law, TERRAMERA, INC., TERRAMERA
LLC and any current or future parents companies, subsidiaries or
affiliates (collectively referred to herein as “Terramera”) and the
Seller offer this product, and the Buyer and User accept it, subject to
the following Conditions of Sale and Warranty which may be varied only
be agreement in writing signed by a duly authorized representative of
Terramera. By using or buying this product, the User or Buyer accepts
the following Conditions, Disclaimer of Warranties and Limitations of
Liability.

CONDITIONS: The Directions For Use of this product reflects the opinion
of experts based on experimental use and tests. The directions are
believed to be adequate and must be followed carefully. Attempts have
been made to eliminate or draw attention to the risks associated with
the use of this product; however, it is impossible to eliminate all
risks inherently associated with the use, handling and transport of this
product. Damage to products, materials, treated surfaces or fabrics,
ineffectiveness or other unintended consequences may result because of
factors such as environmental conditions, the presence of other
materials, the manner of use or application, the use of the product in a
manner inconsistent with its labeling, or other unknown reasons, all of
which are beyond the control of Terramera. All such risks shall be
assumed by the User or Buyer and User and Buyer agree to hold Terramera
and Seller harmless for any claims relating to such factors. Terramera
does not agree to be an insurer of these risks beyond what is expressly
warranted by this label.

Terramera warrants that this product conforms to the chemical
description on the label and is reasonably fit for the purposes referred
to in the Directions For Use when used in accordance with the directions
under normal conditions of use, subject to the inherent risks referred
to above.

DISCLAIMER OF WARRANTIES: To the extent consistent with applicable law,
Terramera or the Seller make no other warranties, guarantees or
representations of any kind, either express or implied, of
merchantability or of fitness for a particular purpose or otherwise,
that extend beyond the statements made on this label. No agent of
Terramera or the Seller is authorized to make any warranties beyond
those contained herein or to modify the warranties contained herein.

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.act, warranty, tort, negligence, strict liability or otherwise, shall
not exceed the purchase price paid for the product, or at Terramera’s
or the Seller’s election, the replacement of product. To the extent
consistent with applicable law, Terramera and the Seller disclaim any
liability for special, consequential, incidental, or indirect damages
resulting from the use, transport, or handling of this product.

TER-CX1 (Concentrate) Version #2.10

28 March 2012

Page   PAGE  6  of   NUMPAGES   6


[Federal Register Volume 86, Number 194 (Tuesday, October 12, 2021)]
[Rules and Regulations]
[Pages 56652-56653]
[FR Doc No: 2021-22105]

=======================================================================
-----------------------------------------------------------------------

ENVIRONMENTAL PROTECTION AGENCY

40 CFR Part 180

[EPA-HQ-OPP-2017-0335; FRL-9000-01-OCSPP]

Pseudomonas Fluorescens Strain ACK55; Exemption From the
Requirement of a Tolerance; Technical Correction

AGENCY: Environmental Protection Agency (EPA).

ACTION: Final rule; correction.

-----------------------------------------------------------------------

SUMMARY: EPA issued a final rule in the Federal Register of September
28, 2020, establishing an exemption from the requirement of a tolerance
for residues of pseudomonas fluorescens strain ACK55 in or on all food
commodities when used in accordance with label directions and good
agricultural practices. This exemption was requested by the IR-4
Project under the Federal Food, Drug, and Cosmetic Act (FFDCA). That
document identified a codified section that had already been assigned
in another final rule that was issued in the Federal Register of
September 25, 2020. This document corrects the final regulation by
identifying a new codified section.

DATES: This final rule correction is effective October 12, 2021.

ADDRESSES: The docket for this action, identified by docket
identification (ID) number EPA-HQ-OPP-2017-0335, is available at http://www.regulations.gov or at the Office of Pesticide Programs Regulatory
Public Docket (OPP Docket) in the Environmental Protection Agency
Docket Center (EPA/DC), West William Jefferson Clinton Bldg., Rm. 3334,
1301 Constitution Ave. NW, Washington, DC 20460-0001. The Public
Reading Room is open from 8:30 a.m. to 4:30 p.m., Monday through
Friday, excluding legal holidays. The telephone number for the Public
Reading Room is<PHONE_NUMBER>, and the telephone number for the OPP
Docket is<PHONE_NUMBER>.
    Due to the public health concerns related to COVID-19, the EPA
Docket Center (EPA/DC) and Reading Room is closed to visitors with
limited exceptions. The staff continues to provide remote customer
service via email, phone, and webform. For the latest status
information on EPA/DC services and docket access, visit https://www.epa.gov/dockets.

FOR FURTHER INFORMATION CONTACT: Charles Smith, Biopesticides and
Pollution Prevention Division (7511P), Office of Pesticide Programs,
Environmental Protection Agency, 1200 Pennsylvania Ave. NW, Washington,
DC 20460-0001; main telephone number:<PHONE_NUMBER>; email address:
[email protected].

SUPPLEMENTARY INFORMATION:

I. Does this action apply to me?

    A list of potentially affected entities is included in the final
rule issued in the Federal Register of September 28, 2020 (85 FR 60716)
(FRL-10013-27).

II. What does this technical correction do?

    EPA issued a final rule in the Federal Register of September 28,
2020 (85 FR 60716) (FRL-10013-27) that established an exemption from
the requirement of a tolerance for residues of pseudomonas fluorescens
strain ACK55 in or on all food commodities when used in accordance with
label directions and good agricultural practices. While establishing
this exemption from the requirement of a tolerance in response to a
petition from the IR-4 Project, EPA inadvertently identified a codified
section that had already been assigned in another final rule that was
issued in the Federal Register of September 25, 2020 (85 FR 60366)
(FRL-10013-33). Unable to use the codified number identified by EPA in
the final rule issued in the Federal Register of September 28, 2020,
the Code of Federal Regulations (CFR) was revised to include the
following text:

    Editorial Note: At 85 FR 60718, Sept. 28, 2020, a second Sec.
180.1379 was added; however, the amendment could not be incorporated
because the section already exists.

    Therefore, with this final rule, EPA is identifying 40 CFR 180.1380
as the codified section for the exemption from the requirement of a
tolerance for residues of pseudomonas fluorescens strain ACK55 in or on
all food commodities when used in accordance with label directions and
good agricultural practices that was established in the final rule
issued in the Federal Register of September 28, 2020 (85 FR 60716)
(FRL-10013-27).

III. Why is this correction issued as a final rule?

    Section 553 of the Administrative Procedure Act (APA) (5 U.S.C.
553(b)(3)(B)) provides that, when an agency for good cause finds that
notice and public procedure are impracticable, unnecessary, or contrary
to the public interest, the agency may issue a final rule without
providing notice and an opportunity for public comment. EPA has
determined that there is good cause for making this technical
correction final without prior proposal and opportunity for comment,
because EPA inadvertently duplicated an existing codified section. EPA
finds that this constitutes good cause under 5 U.S.C. 553(b)(3)(B).

IV. Do any of the statutory and executive order reviews apply to this
action?

    No. For a detailed discussion concerning the statutory and
executive order review, refer to Unit IV. in the final rule of the
September 28, 2020.

V. Congressional Review Act (CRA)

    Pursuant to the CRA (5 U.S.C. 801 et seq.), EPA will submit a
report containing this rule and other required information to the U.S.
Senate, the U.S. House of Representatives, and the Comptroller General
of the United States prior to publication of the rule in the Federal
Register. This action is not a ``major rule'' as defined by 5 U.S.C.
804(2).

List of Subjects in 40 CFR Part 180

    Environmental protection, Administrative practice and procedure,
Agricultural commodities, Pesticides and pests, Reporting and
recordkeeping requirements.

    Dated: September 24, 2021.
Edward Messina,
Director, Office of Pesticide Programs.

    Therefore, for the reasons stated in the preamble, EPA is amending
40 CFR Chapter I as follows:

PART 180--TOLERANCES AND EXEMPTIONS FOR PESTICIDE CHEMICAL RESIDUES
IN FOOD

0
1. The authority citation for part 180 continues to read as follows:

    Authority:  21 U.S.C. 321(q), 346a and 371.

0
2. In subpart D, add Sec.  180.1380 to read as follows:

Sec.  180.1380   Pseudomonas fluorescens strain ACK55; exemption from
the requirement of a tolerance.

    Residues of Pseudomonas fluorescens strain ACK55 are exempt from
the requirement of a tolerance in or on all food commodities when used
in accordance with label directions and good agricultural practices.

[FR Doc. 2021-22105 Filed 10-8-21; 8:45 am]
BILLING CODE 6560-50-P