83 FR 11210 - M7(R1): Assessment and Control of Deoxyribonucleic Acid Reactive (Mutagenic) Impurities in Pharmaceuticals To Limit Potential Carcinogenic Risk; Guidance for Industry; Availability
DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration Federal Register Volume 83, Issue 50 (March 14, 2018)
Food and Drug Administration
Federal Register Volume 83, Issue 50 (March 14, 2018)
| Page Range | 11210-11212 | |
| FR Document | 2018-05118 |
[Federal Register Volume 83, Number 50 (Wednesday, March 14, 2018)] [Notices] [Pages 11210-11212] From the Federal Register Online [www.thefederalregister.org] [FR Doc No: 2018-05118] ----------------------------------------------------------------------- DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2018-D-0740] M7(R1): Assessment and Control of Deoxyribonucleic Acid Reactive (Mutagenic) Impurities in Pharmaceuticals To Limit Potential Carcinogenic Risk; Guidance for Industry; Availability AGENCY: Food and Drug Administration, HHS. ACTION: Notice of availability. ----------------------------------------------------------------------- SUMMARY: The Food and Drug Administration (FDA or Agency) is announcing the availability of a guidance entitled ``M7(R1): Assessment and Control of Deoxyribonucleic Acid (DNA) Reactive (Mutagenic) Impurities in Pharmaceuticals to Limit Potential Carcinogenic Risk.'' This guidance updates and replaces the May 2015 guidance for industry ``M7 Assessment and Control of DNA Reactive (Mutagenic) Impurities in Pharmaceuticals to Limit Potential Carcinogenic Risk.'' This guidance finalizes the draft guidance ``M7(R1) Addendum to ICH M7: Assessment and Control of DNA Reactive (Mutagenic) Impurities in Pharmaceuticals to Limit Potential Carcinogenic Risk,'' issued September 28, 2015 (80 FR 58261). The guidance was prepared under the auspices of the International Council for Harmonisation (ICH), formerly the International Conference on Harmonisation. This M7(R1) document provides guidance on acceptable intakes (AIs), or permissible daily exposures (PDEs), derived for some chemicals that are considered to be mutagens and carcinogens and, are also commonly used in the synthesis of pharmaceuticals or are, useful examples to illustrate the principles for deriving compound-specific intakes described in ICH M7. This document is intended to provide guidance for new drug substances and new drug products during their clinical development and subsequent applications for marketing. DATES: The announcement of the guidance is published in the Federal Register on March 14, 2018. 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 [[Page 11211]] 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-2018-D-0740 for ``M7(R1) Assessment and Control of DNA Reactive (Mutagenic) Impurities in Pharmaceuticals To Limit Potential Carcinogenic Risk.'' 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 office between 9 a.m. and 4 p.m., Monday through Friday. 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.thefederalregister.org/fdsys/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. 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 240-402-8010. 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, 10903 New Hampshire Ave., Bldg. 22, Rm. 4118, Silver Spring, MD 20993-0002, 301-796-1036; or Anne Pilaro, Center for Biologics Evaluation and Research (HFM-17), Food and Drug Administration, 10903 New Hampshire Ave., Bldg. 71, Rm. 4025, Silver Spring, MD 20993-0002, 240-402-8341. Regarding the ICH: Amanda Roache, Center for Drug Evaluation and Research, Food and Drug Administration, 10903 New Hampshire Ave., Bldg. 51, Rm. 1176, Silver Spring, MD 20993-0002, 301-796-4548. SUPPLEMENTARY INFORMATION: I. Background In recent years, regulatory authorities and industry associations from around the world have participated in many important initiatives to promote international harmonization of regulatory requirements under the ICH. FDA has participated in several ICH meetings designed to enhance harmonization and FDA is committed to seeking scientifically based harmonized technical procedures for pharmaceutical development. One of the goals of harmonization is to identify and then reduce differences in technical requirements for drug development among regulatory agencies. ICH was established to provide an opportunity for harmonization initiatives to be developed with input from both regulatory and industry representatives. FDA also seeks input from consumer representatives and others. ICH is concerned with harmonization of technical requirements for the registration of pharmaceutical products for human use among regulators around the world. The six founding members of the ICH are the European Commission; the European Federation of Pharmaceutical Industries Associations; the FDA; the Japanese Ministry of Health, Labour, and Welfare; the Japanese Pharmaceutical Manufacturers Association; and the Pharmaceutical Research and Manufacturers of America. The Standing Members of the ICH Association include Health Canada and Swissmedic. Any party eligible as a Member in accordance with the ICH Articles of Association can apply for membership in writing to the ICH Secretariat. The ICH Secretariat, which coordinates the preparation of documentation, operates as an international nonprofit organization and is funded by the Members of the ICH Association. The ICH Assembly is the overarching body of the Association and includes representatives from each of the ICH members and observers. The Assembly is responsible for the endorsement of draft guidelines and adoption of final guidelines. FDA publishes ICH guidelines as FDA guidance. In the Federal Register of September 28, 2015 (80 FR 58261), FDA published a notice announcing the availability of a draft guidance entitled ``M7(R1) [[Page 11212]] Addendum to ICH M7; Assessment and Control of DNA Reactive (Mutagenic) Impurities in Pharmaceuticals to Limit Potential Carcinogenic Risk,'' available at https://www.thefederalregister.org/fdsys/pkg/FR-2015-09-18/pdf/2015-23389.pdf. The notice gave interested persons an opportunity to submit comments by November 27, 2015. After consideration of the comments received and revisions to the guideline, a final draft of the guideline was submitted to the ICH Assembly and endorsed by the regulatory Agencies in June 2017. This final guidance provides guidance on acceptable intake limits derived for some chemicals that are considered to be mutagenic carcinogens and are also commonly used in the synthesis of pharmaceuticals or are useful examples to illustrate the principles for deriving compound-specific intakes described in the ICH M7 guidance. This guidance is intended to provide guidance for new drug substances and new drug products during their clinical development and subsequent applications for marketing. The default method from ICH M7 of linear extrapolation from the cancer potency estimate, TD 50 is used as the primary method to derive the acceptable intakes for carcinogens with likely mutagenic mode of action. After consideration of the comments received, hydroxylamine monograph was deleted from the final guidance. Relevant editorial changes were also made to improve clarity and to incorporate the ICH M7(R1) Addendum guidance. 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: 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. This guidance is not subject to Executive Order 12866. II. Electronic Access Persons with access to the internet may obtain the guidance at https://www.regulations.gov, https://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/default.htm, or https://www.fda.gov/BiologicsBloodVaccines/GuidanceComplianceRegulatoryInformation/Guidances/default.htm. Dated: March 8, 2018. Leslie Kux, Associate Commissioner for Policy. [FR Doc. 2018-05118 Filed 3-13-18; 8:45 am] BILLING CODE 4164-01-P
![11210 Federal Register / Vol. 83, No. 50 / Wednesday, March 14, 2018 / Notices
2. Besides prescription medical will be asked to send PatientFocused@ DEPARTMENT OF HEALTH AND
treatments, are there other treatments or fda.hhs.gov a brief summary of HUMAN SERVICES
therapies that you currently use to responses to the topic questions by
address your OUD? If so, please April 2, 2018. Panelists will be notified Food and Drug Administration
describe. How well do these treatments of their selection approximately 7 days [Docket No. FDA–2018–D–0740]
or therapies help address the effects of before the public meeting. We will try
OUD that are most bothersome to you? to accommodate all patients and patient M7(R1): Assessment and Control of
3. Of all treatments, therapies, or stakeholders who wish to speak, either Deoxyribonucleic Acid Reactive
other steps that you have taken to through the panel discussion or (Mutagenic) Impurities in
address your OUD, what have you Pharmaceuticals To Limit Potential
audience participation; however, the
found to be most effective in helping Carcinogenic Risk; Guidance for
duration of comments may be limited by
you manage your OUD? Industry; Availability
4. What are the biggest factors that time constraints.
you take into account when making Open Public Comment: There will be AGENCY: Food and Drug Administration,
decisions about seeking out or using time allotted during the meeting for HHS.
treatments for OUD? open public comment. Sign-up for this ACTION: Notice of availability.
5. What specific things would you session will be on a first-come, first-
look for in an ideal treatment for OUD? SUMMARY: The Food and Drug
serve basis on the day of the workshop. Administration (FDA or Agency) is
6. If you had the opportunity to Individuals and organizations with
consider participating in a clinical trial announcing the availability of a
common interests are urged to guidance entitled ‘‘M7(R1): Assessment
studying experimental treatments for consolidate or coordinate and request
OUD, what factors would you consider and Control of Deoxyribonucleic Acid
time for a joint presentation. No (DNA) Reactive (Mutagenic) Impurities
when deciding whether or not to
commercial or promotional material in Pharmaceuticals to Limit Potential
participate?
will be permitted to be presented or Carcinogenic Risk.’’ This guidance
III. Participating in the Public Meeting distributed at the public workshop. updates and replaces the May 2015
Registration: To register for the public Streaming Webcast of the Public guidance for industry ‘‘M7 Assessment
meeting, visit https:// Meeting: This public meeting will also and Control of DNA Reactive
www.eventbrite.com/e/public-meeting- be webcast. Please register for the (Mutagenic) Impurities in
for-patient-focused-drug-development- webcast by visiting https:// Pharmaceuticals to Limit Potential
on-opioid-use-disorder-oud-registration- www.eventbrite.com/e/public-meeting- Carcinogenic Risk.’’ This guidance
42531194949. Please register by April for-patient-focused-drug-development- finalizes the draft guidance ‘‘M7(R1)
11, 2018. Please provide complete Addendum to ICH M7: Assessment and
on-opioid-use-disorder-oud-registration-
contact information for each attendee, Control of DNA Reactive (Mutagenic)
42531194949.
including name, title, affiliation, Impurities in Pharmaceuticals to Limit
address, email, and telephone. Persons If you have never attended a Connect Potential Carcinogenic Risk,’’ issued
without access to the internet can call Pro event before, test your connection at September 28, 2015 (80 FR 58261).
240–402–6525 to register. If you are https://collaboration.fda.gov/common/ The guidance was prepared under the
unable to attend the meeting in person, help/en/support/meeting_test.htm. To auspices of the International Council for
you can register to view a live webcast get a quick overview of the Connect Pro Harmonisation (ICH), formerly the
of the meeting. You will be asked to program, visit https://www.adobe.com/ International Conference on
indicate in your registration if you plan go/connectpro_overview. FDA has Harmonisation. This M7(R1) document
to attend in person or via the webcast. verified the website addresses in this provides guidance on acceptable intakes
Registration is free and based on document, as of the date this document (AIs), or permissible daily exposures
space availability, with priority given to publishes in the Federal Register, but (PDEs), derived for some chemicals that
early registrants. Persons interested in websites are subject to change over time. are considered to be mutagens and
attending this public meeting must carcinogens and, are also commonly
Transcripts: Please be advised that as used in the synthesis of pharmaceuticals
register by April 11, 2018. Early
soon as a transcript of the public or are, useful examples to illustrate the
registration is recommended because
seating is limited; therefore, FDA may meeting is available, it will be accessible principles for deriving compound-
limit the number of participants from at https://www.regulations.gov. It may specific intakes described in ICH M7.
each organization. Registrants will be viewed at the Dockets Management This document is intended to provide
receive confirmation when they have Staff (see ADDRESSES). A link to the guidance for new drug substances and
been accepted. If time and space permit, transcript will also be available on the new drug products during their clinical
onsite registration on the day of the internet at https://www.fda.gov/For development and subsequent
public meeting will be provided Industry/UserFees/PrescriptionDrug applications for marketing.
beginning at 9 a.m. UserFee/ucm591290.htm. DATES: The announcement of the
If you need special accommodations Dated: March 8, 2018. guidance is published in the Federal
because of a disability, please contact Register on March 14, 2018.
Leslie Kux,
Meghana Chalasani (see FOR FURTHER ADDRESSES: You may submit either
INFORMATION CONTACT) no later than Associate Commissioner for Policy.
electronic or written comments on
April 11, 2018. [FR Doc. 2018–05119 Filed 3–13–18; 8:45 am]
Agency guidances at any time as
daltland on DSKBBV9HB2PROD with NOTICES
Panelist Selection: Patients or patient BILLING CODE 4164–01–P follows:
representatives who are interested in
presenting comments as part of the Electronic Submissions
initial panel discussions will be asked Submit electronic comments in the
to indicate in their registration which following way:
topic(s) they wish to address. These • Federal eRulemaking Portal:
patients or patient representatives also https://www.regulations.gov. Follow the
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![11212 Federal Register / Vol. 83, No. 50 / Wednesday, March 14, 2018 / Notices
Addendum to ICH M7; Assessment and Dated: March 8, 2018. Resources and Services Administration,
Control of DNA Reactive (Mutagenic) Leslie Kux, at the contact information listed above.
Impurities in Pharmaceuticals to Limit Associate Commissioner for Policy. SUPPLEMENTARY INFORMATION: The GPE
Potential Carcinogenic Risk,’’ available [FR Doc. 2018–05118 Filed 3–13–18; 8:45 am] Program was established in 2002 to
at https://www.gpo.gov/fdsys/pkg/FR- BILLING CODE 4164–01–P assist American Psychological
2015-09-18/pdf/2015-23389.pdf. The Association (APA) accredited doctoral
notice gave interested persons an programs and internships in meeting the
opportunity to submit comments by DEPARTMENT OF HEALTH AND costs to plan, develop, operate, or
November 27, 2015. HUMAN SERVICES maintain graduate psychology education
After consideration of the comments programs to train health service
Health Resources and Services psychologists to work with vulnerable
received and revisions to the guideline, Administration populations. The purpose of the current
a final draft of the guideline was
program (Funding Opportunity
submitted to the ICH Assembly and Proposed Changes to the Graduate Announcement HRSA–16–059) is to
endorsed by the regulatory Agencies in Psychology Education Program prepare doctoral-level psychologists to
June 2017. provide behavioral health care,
AGENCY: Health Resources and Services
This final guidance provides guidance including mental health and substance
Administration (HRSA), Department of
on acceptable intake limits derived for use disorder prevention and treatment
Health and Human Services.
some chemicals that are considered to services, in settings that provide
be mutagenic carcinogens and are also ACTION: Request for Public Comment on integrated primary and behavioral
commonly used in the synthesis of the Graduate Psychology Education health services to underserved and/or
pharmaceuticals or are useful examples Program. rural populations. The program is
to illustrate the principles for deriving designed to foster an integrated and
SUMMARY: The Graduate Psychology
compound-specific intakes described in interprofessional approach to address
Education (GPE) Program is authorized
the ICH M7 guidance. This guidance is access to behavioral health care for
by section 756 of the Public Health underserved and/or rural populations.
intended to provide guidance for new Service Act and administered by HRSA.
drug substances and new drug products Given the value of feedback from
The program provides financial support stakeholders, HRSA is seeking
during their clinical development and to organizations and institutions that
subsequent applications for marketing. comments from interested parties
train doctoral-level psychologists. This including current and former grant
The default method from ICH M7 of notice seeks public comment to inform
linear extrapolation from the cancer recipients, former applicants to the
and guide policy and planning program, doctoral psychology schools
potency estimate, TD50 is used as the associated with the GPE Program. and programs, and health care delivery
primary method to derive the acceptable
DATES: Individuals and organizations sites that provide behavioral health
intakes for carcinogens with likely
interested in providing information experiential training to students. The
mutagenic mode of action. After must submit written comments no later purpose is to identify doctoral-level
consideration of the comments received, than April 13, 2018. To receive health service psychologist training
hydroxylamine monograph was deleted consideration, comments must be needs, salient issues and challenges in
from the final guidance. Relevant received no later than 11:59 p.m. the delivery of behavioral health
editorial changes were also made to Eastern Time on that date. services, including substance use, and
improve clarity and to incorporate the to provide individual recommendations
ADDRESSES: Interested parties should
ICH M7(R1) Addendum guidance. to maximize the reach, capacity and
submit their comments to Cynthia
This guidance is being issued Harne, Public Health Analyst and success of the GPE Program in
consistent with FDA’s good guidance Project Officer for the GPE Program, addressing Opioid Use Disorder and
practices regulation (21 CFR 10.115). Division of Nursing and Public Health, other behavioral health concerns. This
The guidance represents the current Behavioral and Public Health Branch, information may be used by HRSA will
thinking of FDA on ‘‘M7: Assessment Bureau of Health Workforce, HRSA, consider the input as it develops future
and Control of DNA Reactive 5600 Fishers Lane, Room 11N–90C, technical assistance and funding
(Mutagenic) Impurities in Rockville, Maryland 20857; phone (301) opportunities, and strategic planning to
Pharmaceuticals to Limit Potential 443–7661; fax (301) 443–0791; or email meet the training demands of the
Carcinogenic Risk.’’ It does not establish charne@hrsa.gov. Please include the behavioral health workforce.
any rights for any person and is not title of this notice, ‘‘Request for Graduate Psychology Program in FY
binding on FDA or the public. You can Comment: GPE Program’’ in the subject 2019—Proposal for Public Comment
use an alternative approach if it satisfies line of the email. Response to this
the requirements of the applicable HRSA seeks comments on how the
request is voluntary. Responders are free
statutes and regulations. This guidance GPE program (and the students it
to address any or all of the questions
is not subject to Executive Order 12866. supports) can help address the opioid
listed below. This request is for
epidemic. In your comments, please
II. Electronic Access information and planning purposes only
address one or more of the following:
and should not be construed as a 1. What do you see as the most
Persons with access to the internet solicitation or as an obligation on the prevalent behavioral health and public
may obtain the guidance at https:// part of the federal government. All health trends or concerns that should be
daltland on DSKBBV9HB2PROD with NOTICES
www.regulations.gov, https:// submitted comments will be available to addressed in developing the
www.fda.gov/Drugs/Guidance the public by request in their entirety. psychologist workforce?
ComplianceRegulatoryInformation/ FOR FURTHER INFORMATION CONTACT: 2. What do you see as the role for
Guidances/default.htm, or https:// Cynthia Harne, Public Health Analyst, doctoral-level health psychologists in
www.fda.gov/BiologicsBloodVaccines/ Division of Nursing and Public Health, addressing the opioid epidemic?
GuidanceComplianceRegulatory Behavioral and Public Health Branch, 3. What are the didactic and
Information/Guidances/default.htm. Bureau of Health Workforce, Health experiential training needs in preparing
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Document Created: 2018-03-14 01:06:16
Document Modified: 2018-03-14 01:06:16
| Category | Regulatory Information | |
| Collection | Federal Register | |
| sudoc Class | AE 2.7: GS 4.107: AE 2.106: | |
| Publisher | Office of the Federal Register, National Archives and Records Administration | |
| Section | Notices | |
| Action | Notice of availability. | |
| Dates | The announcement of the guidance is published in the Federal Register on March 14, 2018. | |
| Contact | Regarding the guidance: Aisar Atrakchi, Center for Drug Evaluation and Research, Food and Drug Administration, 10903 New Hampshire Ave., Bldg. 22, Rm. 4118, Silver Spring, MD 20993-0002, 301-796-1036; or Anne Pilaro, Center for Biologics Evaluation and Research (HFM-17), Food and Drug Administration, 10903 New Hampshire Ave., Bldg. 71, Rm. 4025, Silver Spring, MD 20993-0002, 240-402-8341. | |
| FR Citation | 83 FR 11210 |
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