83 FR 21781 - Framework for Assessment of Drug-Drug Interactions for Therapeutic Proteins; Establishment of a Public Docket; Request for Information and Comments
DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration Federal Register Volume 83, Issue 91 (May 10, 2018)
Food and Drug Administration
Federal Register Volume 83, Issue 91 (May 10, 2018)
| Page Range | 21781-21782 | |
| FR Document | 2018-09931 |
[Federal Register Volume 83, Number 91 (Thursday, May 10, 2018)] [Notices] [Pages 21781-21782] From the Federal Register Online [www.thefederalregister.org] [FR Doc No: 2018-09931] [[Page 21781]] ----------------------------------------------------------------------- DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2018-N-1415] Framework for Assessment of Drug-Drug Interactions for Therapeutic Proteins; Establishment of a Public Docket; Request for Information and Comments AGENCY: Food and Drug Administration, HHS. ACTION: Notice; establishment of a public docket; request for information and comments. ----------------------------------------------------------------------- SUMMARY: The Food and Drug Administration (FDA or Agency) is establishing a public docket to assist with its development of a policy/guidance document on the assessment of drug-drug interactions (DDIs) for therapeutic proteins (TPs). The Agency split the 2012 DDI draft guidance into two draft guidance documents published in October 2017: ``In Vitro Metabolism- and Transporter-Mediated Drug-Drug Interaction Studies'' and ``Clinical Drug Interaction Studies--Study Design, Data Analysis, and Clinical Implications.'' The two guidance documents focus on enzyme- and transporter-based DDIs and do not include a discussion on TPs, which was originally included in the 2012 guidance. The Agency is currently revisiting the framework for assessment of DDIs for TPs outlined in the draft 2012 DDI guidance to offer timely and actionable information pertaining to DDIs for TPs and is seeking public input to assist in updating or creating a new framework. DATES: Although you can comment at any time, to ensure that the Agency considers your comment in our development of recommendations, submit either electronic or written information and comments by July 9, 2018. ADDRESSES: You may submit comments 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-2018-N-1415 for ``Framework for Assessment of Drug-Drug Interactions for Therapeutic Proteins.'' 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. 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. FOR FURTHER INFORMATION CONTACT: Regarding human prescription drugs: Julie Chronis, Center for Drug Evaluation and Research, Food and Drug Administration, 10903 New Hampshire Ave., Bldg. 51, Rm. 3203, Silver Spring, MD 20993-0002, 301- 796-1200. Regarding human prescription biological products: Stephen Ripley, Center for Biologics Evaluation and Research, Food and Drug Administration, 10903 New Hampshire Ave., Bldg. 71, Rm. 7301, Silver Spring, MD 20993-0002, 240-402-7911. SUPPLEMENTARY INFORMATION: I. Background Concurrent use of more than one prescription drug is common. A Centers for Disease Control and Prevention survey reports that about 20 percent of U.S. adults take three or more prescription drugs; and among adults age 65 and older, 40 percent take five or more medications.\1\ Taking more than one drug at a time can result in DDIs which can result in toxicities or loss of efficacy. It is impractical to evaluate the impact of every possible drug combination. Therefore, the FDA [[Page 21782]] follows a systematic risk-based approach for DDI assessment. --------------------------------------------------------------------------- \1\ Centers for Disease Control and Prevention's National Health and Nutrition Examination Survey: https://www.cdc.gov/nchs/data/hus/hus16.pdf#079. --------------------------------------------------------------------------- Two draft guidance documents, when finalized, which are intended to assist drug developers in the planning and evaluation of the DDI potential of their drug during development were published in October 2017 entitled ``Clinical Drug Interaction Studies--Study Design, Data Analysis, and Clinical Implications,'' and ``In Vitro Metabolism- and Transporter-Mediated Drug-Drug Interaction Studies.'' \2\ These two draft guidances replaced the 2012 draft guidance entitled ``Drug Interaction Studies--Study Design, Data Analysis, Implications for Dosing, and Labeling Recommendations.'' The 2017 draft guidance documents focus on enzyme- and transporter-based DDIs; however, they do not discuss TPs. --------------------------------------------------------------------------- \2\ ``Clinical Drug Interaction Studies--Study Design, Data Analysis, and Clinical Implications'' can be found at https://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM292362.pdf; provide comments to this guidance using docket number FDA-2017-D-596. ``In Vitro Metabolism- and Transporter-Mediated Drug-Drug Interaction Studies'' can be found at https://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM581965.pdf; provide comments to this guidance using docket number FDA-2017-D-5961. --------------------------------------------------------------------------- The 2012 guidance recommended DDI assessment for TPs in three scenarios: (1) For cytokine or cytokine modulators, (2) for a known or suspected mechanism of DDI not related to effects on Cytochrome P450 enzymes or transporters, and (3) for when a TP is used in combination with another drug. The Agency now plans to revisit the previous framework for the assessment of DDIs for TPs that was included in the 2012 draft guidance. We are seeking public input on the revision and development of a framework to address DDIs for TPs with the goal of publishing this framework in a short policy/guidance document. II. Additional Issues for Consideration and Request for Information Interested persons are invited to provide detailed information and comments on the approach to the DDI assessment of TPs. Please read the information above regarding the submission of comments and confidential information. FDA is particularly interested in responses to the following overarching questions: 1. In what scenarios/circumstances and for which classes of TPs should DDI assessment be performed? Please provide rationale for your suggestions including available data and scientific principles to inform the considerations. 2. For circumstances when DDI assessments are necessary: a. What types of assessments can be useful (e.g., in vitro studies, dedicated clinical studies, population pharmacokinetic analyses, physiologically based pharmacokinetic analyses)? Please discuss the challenges and limitations with each type of assessment, and, as necessary, organize any discussions by the class of TP. b. What are the study design considerations (e.g., population, analytes) for the types of assessments discussed in bullet 2a. above? Please describe the rationale for any design considerations proposed. FDA will consider all information and comments submitted. Dated: May 4, 2018. Leslie Kux, Associate Commissioner for Policy. [FR Doc. 2018-09931 Filed 5-9-18; 8:45 am] BILLING CODE 4164-01-P
![Federal Register / Vol. 83, No. 91 / Thursday, May 10, 2018 / Notices 21781
DEPARTMENT OF HEALTH AND comment does not include any Staff. If you do not wish your name and
HUMAN SERVICES confidential information that you or a contact information to be made publicly
third party may not wish to be posted, available, you can provide this
Food and Drug Administration such as medical information, your or information on the cover sheet and not
anyone else’s Social Security number, or in the body of your comments and you
[Docket No. FDA–2018–N–1415]
confidential business information, such must identify this information as
Framework for Assessment of Drug- as a manufacturing process. Please note ‘‘confidential.’’ Any information marked
Drug Interactions for Therapeutic that if you include your name, contact as ‘‘confidential’’ will not be disclosed
Proteins; Establishment of a Public information, or other information that except in accordance with 21 CFR 10.20
Docket; Request for Information and identifies you in the body of your and other applicable disclosure law. For
Comments comments, that information will be more information about FDA’s posting
posted on https://www.regulations.gov. of comments to public dockets, see 80
AGENCY: Food and Drug Administration, • If you want to submit a comment
HHS. FR 56469, September 18, 2015, or access
with confidential information that you
ACTION: Notice; establishment of a the information at: https://www.gpo.gov/
do not wish to be made available to the
public docket; request for information fdsys/pkg/FR-2015-09-18/pdf/2015-
public, submit the comment as a
and comments. written/paper submission and in the 23389.pdf.
manner detailed (see ‘‘Written/Paper Docket: For access to the docket to
SUMMARY: The Food and Drug Submissions’’ and ‘‘Instructions’’). read background documents or the
Administration (FDA or Agency) is electronic and written/paper comments
establishing a public docket to assist Written/Paper Submissions
received, go to https://
with its development of a policy/ Submit written/paper submissions as www.regulations.gov and insert the
guidance document on the assessment follows:
of drug-drug interactions (DDIs) for docket number, found in brackets in the
• Mail/Hand delivery/Courier (for heading of this document, into the
therapeutic proteins (TPs). The Agency written/paper submissions): Dockets
split the 2012 DDI draft guidance into ‘‘Search’’ box and follow the prompts
Management Staff (HFA–305), Food and and/or go to the Dockets Management
two draft guidance documents Drug Administration, 5630 Fishers
published in October 2017: ‘‘In Vitro Staff, 5630 Fishers Lane, Rm. 1061,
Lane, Rm. 1061, Rockville, MD 20852.
Metabolism- and Transporter-Mediated Rockville, MD 20852.
• For written/paper comments
Drug-Drug Interaction Studies’’ and submitted to the Dockets Management FOR FURTHER INFORMATION CONTACT:
‘‘Clinical Drug Interaction Studies— Staff, FDA will post your comment, as
Study Design, Data Analysis, and Regarding human prescription drugs:
well as any attachments, except for
Clinical Implications.’’ The two Julie Chronis, Center for Drug
information submitted, marked and
guidance documents focus on enzyme- Evaluation and Research, Food and
identified, as confidential, if submitted
and transporter-based DDIs and do not Drug Administration, 10903 New
as detailed in ‘‘Instructions.’’
include a discussion on TPs, which was Instructions: All submissions received Hampshire Ave., Bldg. 51, Rm. 3203,
originally included in the 2012 must include the Docket No. FDA– Silver Spring, MD 20993–0002, 301–
guidance. The Agency is currently 2018–N–1415 for ‘‘Framework for 796–1200.
revisiting the framework for assessment Assessment of Drug-Drug Interactions Regarding human prescription
of DDIs for TPs outlined in the draft for Therapeutic Proteins.’’ Received biological products: Stephen Ripley,
2012 DDI guidance to offer timely and comments will be placed in the docket Center for Biologics Evaluation and
actionable information pertaining to and, except for those submitted as Research, Food and Drug
DDIs for TPs and is seeking public input ‘‘Confidential Submissions,’’ publicly
to assist in updating or creating a new Administration, 10903 New Hampshire
viewable at https://www.regulations.gov Ave., Bldg. 71, Rm. 7301, Silver Spring,
framework. or at the Dockets Management Staff MD 20993–0002, 240–402–7911.
DATES: Although you can comment at between 9 a.m. and 4 p.m., Monday
any time, to ensure that the Agency through Friday. SUPPLEMENTARY INFORMATION:
considers your comment in our • Confidential Submissions—To I. Background
development of recommendations, submit a comment with confidential
submit either electronic or written information that you do not wish to be Concurrent use of more than one
information and comments by July 9, made publicly available, submit your prescription drug is common. A Centers
2018. comments only as a written/paper for Disease Control and Prevention
ADDRESSES: You may submit comments submission. You should submit two survey reports that about 20 percent of
as follows: copies total. One copy will include the U.S. adults take three or more
information you claim to be confidential prescription drugs; and among adults
Electronic Submissions with a heading or cover note that states age 65 and older, 40 percent take five or
Submit electronic comments in the ‘‘THIS DOCUMENT CONTAINS
more medications.1 Taking more than
following way: CONFIDENTIAL INFORMATION.’’ The
one drug at a time can result in DDIs
• Federal eRulemaking Portal: Agency will review this copy, including
which can result in toxicities or loss of
https://www.regulations.gov. Follow the the claimed confidential information, in
efficacy. It is impractical to evaluate the
daltland on DSKBBV9HB2PROD with NOTICES
instructions for submitting comments. its consideration of comments. The
Comments submitted electronically, second copy, which will have the impact of every possible drug
including attachments, to https:// claimed confidential information combination. Therefore, the FDA
www.regulations.gov will be posted to redacted/blacked out, will be available
the docket unchanged. Because your for public viewing and posted on 1 Centers for Disease Control and Prevention’s
comment will be made public, you are https://www.regulations.gov. Submit National Health and Nutrition Examination Survey:
solely responsible for ensuring that your both copies to the Dockets Management https://www.cdc.gov/nchs/data/hus/hus16.pdf#079.
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![21782 Federal Register / Vol. 83, No. 91 / Thursday, May 10, 2018 / Notices
follows a systematic risk-based 2. For circumstances when DDI method in toxicokinetic studies and
approach for DDI assessment. assessments are necessary: acknowledges the benefits (and some
Two draft guidance documents, when a. What types of assessments can be limitations) of the use of microsampling.
finalized, which are intended to assist useful (e.g., in vitro studies, dedicated DATES: The announcement of the
drug developers in the planning and clinical studies, population guidance is published in the Federal
evaluation of the DDI potential of their pharmacokinetic analyses, Register on May 10, 2018.
drug during development were physiologically based pharmacokinetic ADDRESSES: You may submit either
published in October 2017 entitled analyses)? Please discuss the challenges electronic or written comments on
‘‘Clinical Drug Interaction Studies— and limitations with each type of Agency guidances at any time as
Study Design, Data Analysis, and assessment, and, as necessary, organize follows:
Clinical Implications,’’ and ‘‘In Vitro any discussions by the class of TP.
Metabolism- and Transporter-Mediated b. What are the study design Electronic Submissions
Drug-Drug Interaction Studies.’’ 2 These considerations (e.g., population, Submit electronic comments in the
two draft guidances replaced the 2012 analytes) for the types of assessments following way:
draft guidance entitled ‘‘Drug discussed in bullet 2a. above? Please • Federal eRulemaking Portal:
Interaction Studies—Study Design, Data describe the rationale for any design https://www.regulations.gov. Follow the
Analysis, Implications for Dosing, and considerations proposed. instructions for submitting comments.
Labeling Recommendations.’’ The 2017 FDA will consider all information and Comments submitted electronically,
draft guidance documents focus on comments submitted. including attachments, to https://
enzyme- and transporter-based DDIs; Dated: May 4, 2018. www.regulations.gov will be posted to
however, they do not discuss TPs. Leslie Kux, the docket unchanged. Because your
The 2012 guidance recommended DDI comment will be made public, you are
Associate Commissioner for Policy.
assessment for TPs in three scenarios: solely responsible for ensuring that your
(1) For cytokine or cytokine modulators, [FR Doc. 2018–09931 Filed 5–9–18; 8:45 am]
comment does not include any
(2) for a known or suspected mechanism BILLING CODE 4164–01–P
confidential information that you or a
of DDI not related to effects on third party may not wish to be posted,
Cytochrome P450 enzymes or such as medical information, your or
transporters, and (3) for when a TP is DEPARTMENT OF HEALTH AND
HUMAN SERVICES anyone else’s Social Security number, or
used in combination with another drug. confidential business information, such
The Agency now plans to revisit the Food and Drug Administration as a manufacturing process. Please note
previous framework for the assessment that if you include your name, contact
of DDIs for TPs that was included in the [Docket No. FDA–2016–D–2513]
information, or other information that
2012 draft guidance. We are seeking identifies you in the body of your
public input on the revision and S3A Guidance: Note for Guidance on
Toxicokinetics: The Assessment of comments, that information will be
development of a framework to address posted on https://www.regulations.gov.
DDIs for TPs with the goal of publishing Systemic Exposure in Toxicity Studies:
Focus on Microsampling—Questions • If you want to submit a comment
this framework in a short policy/ with confidential information that you
guidance document. and Answers; International Council for
Harmonisation; Guidance for Industry; do not wish to be made available to the
II. Additional Issues for Consideration Availability public, submit the comment as a
and Request for Information written/paper submission and in the
AGENCY: Food and Drug Administration, manner detailed (see ‘‘Written/Paper
Interested persons are invited to
HHS. Submissions’’ and ‘‘Instructions’’).
provide detailed information and
comments on the approach to the DDI ACTION: Notice of availability. Written/Paper Submissions
assessment of TPs. Please read the SUMMARY: The Food and Drug Submit written/paper submissions as
information above regarding the Administration (FDA or Agency) is follows:
submission of comments and announcing the availability of a • Mail/Hand delivery/Courier (for
confidential information. FDA is guidance entitled ‘‘S3A Guidance: Note written/paper submissions): Dockets
particularly interested in responses to for Guidance on Toxicokinetics: The Management Staff (HFA–305), Food and
the following overarching questions: Assessment of Systemic Exposure in Drug Administration, 5630 Fishers
1. In what scenarios/circumstances
Toxicity Studies: Focus on Lane, Rm. 1061, Rockville, MD 20852.
and for which classes of TPs should DDI
Microsampling—Questions and • For written/paper comments
assessment be performed? Please
Answers.’’ The guidance was prepared submitted to the Dockets Management
provide rationale for your suggestions
under the auspices of the International Staff, FDA will post your comment, as
including available data and scientific
Council for Harmonisation (ICH), well as any attachments, except for
principles to inform the considerations.
formerly the International Conference information submitted, marked and
2 ‘‘Clinical Drug Interaction Studies—Study
on Harmonisation. This question-and- identified, as confidential, if submitted
Design, Data Analysis, and Clinical Implications’’ answer (Q&A) guidance provides as detailed in ‘‘Instructions.’’
can be found at https://www.fda.gov/downloads/ additional information to facilitate Instructions: All submissions received
Drugs/GuidanceComplianceRegulatoryInformation/ interpretation of the guideline for must include the Docket No. FDA–
Guidances/UCM292362.pdf; provide comments to industry ‘‘S3A Toxicokinetics: The 2016–D–2513 for ‘‘S3A Guidance: Note
daltland on DSKBBV9HB2PROD with NOTICES
this guidance using docket number FDA–2017–D–
596. Assessment of Systemic Exposure in for Guidance on Toxicokinetics: The
‘‘In Vitro Metabolism- and Transporter-Mediated Toxicity Studies’’ (S3A guidance), Assessment of Systemic Exposure in
Drug-Drug Interaction Studies’’ can be found at especially to address the benefit and use Toxicity Studies: Focus on
https://www.fda.gov/downloads/Drugs/ of microsampling techniques in main Microsampling—Questions and
GuidanceComplianceRegulatoryInformation/
Guidances/UCM581965.pdf; provide comments to
study animals. The Q&A guidance is Answers.’’ Received comments will be
this guidance using docket number FDA–2017–D– intended to provide points to consider placed in the docket and, except for
5961. before incorporating the microsampling those submitted as ‘‘Confidential
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Document Created: 2018-11-02 09:47:14
Document Modified: 2018-11-02 09:47:14
| 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; establishment of a public docket; request for information and comments. | |
| Dates | Although you can comment at any time, to ensure that the Agency considers your comment in our development of recommendations, submit either electronic or written information and comments by July 9, 2018. | |
| Contact | Regarding human prescription drugs: Julie Chronis, Center for Drug Evaluation and Research, Food and Drug Administration, 10903 New Hampshire Ave., Bldg. 51, Rm. 3203, Silver Spring, MD 20993-0002, 301- 796-1200. | |
| FR Citation | 83 FR 21781 |
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