Federal Register / Vol. 82, No. 205 / Wednesday, October 25, 2017 / Notices 49373 

level of risk. Clinically relevant DDIs 

between an investigational drug and 

other drugs should therefore: (1) Be 

defined during drug development as 

part of an adequate assessment of the 

drug’s overall benefit/risk profile; (2) be 

known at the time of the drug’s 

approval; and (3) be communicated in 

labeling. These two draft guidances are 

intended to assist drug developers in the 

planning and evaluation of DDI 

potential during drug development. In 

particular, the in vitro DDI guidance 

focuses on in vitro experimental 

approaches for evaluating metabolizing 

enzyme- and transporter-based drug 

interaction potential, and how to 

extrapolate in vitro data to decide on the 

need for clinical DDI studies. The 

appendix of the in vitro DDI guidance 

includes considerations in the choice of 

in vitro experimental systems, key 

issues regarding in vitro experimental 

conditions, and a more detailed 

explanation of model-based DDI 

prediction strategies. If in vitro 

assessments indicate the need to 

conduct clinical DDI studies, sponsors 

should consult the related clinical DDI 

guidance. The clinical DDI guidance 

focuses on clinical studies that evaluate 

DDIs that alter a drug’s 

pharmacokinetics by modulating the 

effects of drug metabolizing enzymes 

and/or transporters and advises 

sponsors on the timing and design of the 

clinical studies, interpretation of the 

results, and options for DDI 

management in patients. Together, the 

two draft guidances describe a 

systematic, risk-based approach to 

evaluation and communication of DDIs. 

In the Federal Register of February 

21, 2012 (77 FR 9946), FDA announced 

the availability of a revised draft 

guidance entitled ‘‘Drug Interaction 

Studies—Study Design, Data Analysis, 

Implications for Dosing, and Labeling 

Recommendations.’’ We received 

comments on the 2012 draft guidance 

and have considered these comments 

while updating the information in the 

two draft guidances. In addition, new 

developments in the field have been 

incorporated to reflect the Agency’s 

current thinking. 

The Agency decided to divide the 

2012 draft guidance into two guidances 

with one focusing on in vitro DDI 

evaluation and the other focusing on 

clinical DDI evaluation. We are 

publishing the two draft guidances to 

collect additional public comments. 

These new draft guidances focus on 

metabolism- and transporter-based drug 

interactions. Other types of interactions, 

e.g., drug-therapeutic protein 

interactions and pH-dependent drug 

interactions, are not included. Separate 

guidances will be developed to cover 

other types of DDIs. In addition, a draft 

guidance specific to Section 7 (Drug 

Interactions) labeling will be developed 

to delineate the communication of DDI 

information in labeling. 

These two draft guidances are being 

issued consistent with FDA’s good 

guidance practices regulation (21 CFR 

10.115). These draft guidances, when 

finalized, will represent the Agency’s 

current thinking on ‘‘In Vitro 

Metabolism- and Transporter-Mediated 

Drug-Drug Interaction Studies’’ and 

‘‘Clinical Drug Interaction Studies— 

Study Design, Data Analysis, and 

Clinical Implications.’’ 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. 

These guidances are not subject to 

Executive Order 12866. 

II. Paperwork Reduction Act of 1995 

These draft guidances refer to 

previously approved collections of 

information found in FDA regulations. 

These collections of information are 

subject to review by the Office of 

Management and Budget (OMB) under 

the Paperwork Reduction Act of 1995 

(44 U.S.C. 3501–3520). The collections 

of information in 21 CFR 314.50(d) have 

been approved under OMB control 

number 0910–0001. 

III. Electronic Access 

Persons with access to the internet 

may obtain the draft guidance at either 

https://www.fda.gov/Drugs/Guidance

ComplianceRegulatoryInformation/ 

Guidances/default.htm or https://

www.regulations.gov. 

Dated: October 19, 2017. 

Anna K. Abram, 

Deputy Commissioner for Policy, Planning, 

Legislation, and Analysis. 

[FR Doc. 2017–23102 Filed 10–24–17; 8:45 am] 

BILLING CODE 4164–01–P 

DEPARTMENT OF HEALTH AND 

HUMAN SERVICES 

Food and Drug Administration 

[Docket No. FDA–2017–D–5966] 

Breakthrough Devices Program; Draft 

Guidance for Industry and Food and 

Drug Administration Staff; 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 the draft 

guidance entitled ‘‘Breakthrough 

Devices Program; Draft Guidance for 

Industry and Food and Drug 

Administration Staff.’’ This guidance 

document describes policies that FDA 

intends to use to implement the new 

Breakthrough Devices Program, 

established by the 21st Century Cures 

Act (Cures Act). The Breakthrough 

Devices Program supersedes and 

combines elements from FDA’s 

Expedited Access Pathway (EAP), 

which was intended to facilitate the 

development and expedite review of 

breakthrough technologies, as well as 

the Priority Review Program, which 

implemented statutory criteria for 

granting priority review to premarket 

approval applications (PMAs) and 

applied those criteria to other types of 

premarket submissions for medical 

devices. This draft guidance clarifies 

certain principles and features of the 

new program, the designation criteria 

for Breakthrough Devices, the 

designation request review process, the 

process for withdrawing from the 

program, as well as the recommended 

information device manufacturers 

should provide in their designation 

request for entrance into the program. 

This draft guidance is not final nor is it 

in effect at this time. 

DATES: Submit either electronic or 

written comments on the draft guidance 

by December 26, 2017 to ensure that the 

Agency considers your comment on this 

draft guidance before it begins work on 

the final version of the guidance. 

ADDRESSES: You may submit comments 

on any guidance 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. 


sradovich on DSK3GMQ082PROD with NOTICES
49374 Federal Register / Vol. 82, No. 205 / Wednesday, October 25, 2017 / Notices 

• 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– 

2017–D–5966 for ‘‘Breakthrough 

Devices Program; Draft Guidance for 

Industry and Food and Drug 

Administration Staff.’’ 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.gpo.gov/ 

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. 

You may submit comments on any 

guidance at any time (see 21 CFR 

10.115(g)(5)). 

An electronic copy of the guidance 

document is available for download 

from the internet. See the 

SUPPLEMENTARY INFORMATION section for 

information on electronic access to the 

guidance. Submit written requests for a 

single hard copy of the draft guidance 

document entitled ‘‘Breakthrough 

Devices Program; Draft Guidance for 

Industry and Food and Drug 

Administration Staff’’ to the Office of 

the Center Director, Guidance and 

Policy Development, Center for Devices 

and Radiological Health, Food and Drug 

Administration, 10903 New Hampshire 

Ave., Bldg. 66, Rm. 5431, Silver Spring, 

MD 20993–0002, or the Office of 

Communication, Outreach, and 

Development, Center for Biologics 

Evaluation and Research, 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 

request. 

FOR FURTHER INFORMATION CONTACT: Erin 

Cutts, Center for Devices and 

Radiological Health, Food and Drug 

Administration, 10903 New Hampshire 

Ave., Bldg. 66, Rm. 1625, Silver Spring, 

MD 20993–0002, 301–796–6307; or 

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 

FDA is issuing this draft guidance to 

describe policies that FDA intends to 

use to implement section 515B of the 

Federal Food, Drug, and Cosmetic Act 

(FD&C Act) (21 U.S.C. 360e–3, as 

created by section 3051 of the Cures Act 

(Pub. L. 114–255) and section 901 of the 

FDA Reauthorization Act of 2017 (Pub. 

L. 115–52) (the ‘‘Breakthrough Devices 

Program’’). The Breakthrough Devices 

Program is a voluntary program for 

certain medical devices that provide for 

more effective treatment or diagnosis of 

life-threatening or irreversibly 

debilitating diseases or conditions. This 

program is intended to help patients 

have more timely access to these 

medical devices by expediting their 

development, assessment, and review, 

while preserving the statutory standards 

for premarket approval, clearance of a 

premarket notification (510(k)), and 

marketing authorization via the De Novo 

classification process, consistent with 

the Agency’s statutory mission to 

protect and promote public health. No 

later than 1 year after the date of 

enactment of the Cures Act, FDA is 

required to issue this draft guidance, 

which sets forth the process by which 

a person may seek a Breakthrough 

Device designation, provides a template 

for designation requests, identifies the 

criteria that FDA will use in evaluating 

designation requests, and identifies the 

criteria and processes FDA will use to 

assign and train a team of staff to review 

breakthrough devices after designation 

has been granted. See section 515B(f) of 

the FD&C Act. 

As part of the Breakthrough Devices 

Program, FDA intends to provide 

interactive and timely communication 

with the sponsor during development 

and throughout the review process for 

devices designated as Breakthrough 

Devices under section 515B(d)(1) of the 

FD&C Act and grant priority to the 

review of associated Q-submissions, 

investigational device exemption (IDE) 

applications, PMAs, De Novo 

classification requests, and premarket 

notifications (510(k)s). In addition, for 

Breakthrough Devices subject to PMA, 

FDA may consider the amount of data 

that may be collected in the postmarket 

setting, rather than premarket, and the 

level of acceptable uncertainty in the 

benefit-risk profile at the time of 

approval. Getting the right balance 

between premarket and postmarket data 

collection—specifically, where 

appropriate, a greater reliance on 

postmarket collection—can reduce the 

extent of premarket data submission. 

Collectively, these and the other 

principles of the program described in 

this draft guidance are intended to 

support a least-burdensome approach 

for expediting patient access to 

Breakthrough Devices. 

The Breakthrough Devices Program 

supersedes the EAP, which launched in 

2015. The Breakthrough Devices 

Program contains features of the EAP as 

well as the Innovation Pathway (first 

piloted in 2011), both of which were 

intended to facilitate the development 


sradovich on DSK3GMQ082PROD with NOTICES
Federal Register / Vol. 82, No. 205 / Wednesday, October 25, 2017 / Notices 49375 

and expedite the review of breakthrough 

technologies. 

The Breakthrough Devices Program 

also supersedes the Priority Review 

Program, which implemented statutory 

criteria for granting priority review to 

PMA submissions for medical devices, 

applied those criteria to other types of 

premarket submissions for medical 

devices, and included standard 

procedures to achieve an efficient 

priority review process. 

II. Significance of Guidance 

This draft guidance is being issued 

consistent with FDA’s good guidance 

practices regulation (21 CFR 10.115). 

The draft guidance, when finalized, will 

represent the current thinking of FDA 

on ‘‘Breakthrough Devices Program; 

Draft Guidance for Industry and Food 

and Drug Administration Staff.’’ 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. 

III. Electronic Access 

Persons interested in obtaining a copy 

of the draft guidance may do so by 

downloading an electronic copy from 

the internet. A search capability for all 

Center for Devices and Radiological 

Health guidance documents is available 

at https://www.fda.gov/MedicalDevices/ 

DeviceRegulationandGuidance/ 

GuidanceDocuments/default.htm. 

Guidance documents are also available 

at https://www.fda.gov/BiologicsBlood

Vaccines/GuidanceCompliance

RegulatoryInformation/default.htm or 

https://www.regulations.gov. Persons 

unable to download an electronic copy 

of ‘‘Breakthrough Devices Program’’ may 

send an email request to CDRHGuidance@fda.hhs.gov to receive an 

electronic copy of the document. Please 

use the document number 1833 to 

identify the guidance you are 

requesting. 

IV. Paperwork Reduction Act of 1995 

This guidance refers to previously 

approved collections of information 

found in FDA regulations. These 

collections of information are subject to 

review by the Office of Management and 

Budget (OMB) under the Paperwork 

Reduction Act of 1995 (44 U.S.C. 3501– 

3520). The collections of information in 

21 CFR part 807, subpart E have been 

approved under OMB control number 

0910–0120; the collections of 

information for De Novo classification 

requests have been approved under 

OMB control number 0910–0844; the 

collections of information in 21 CFR 

part 812 have been approved under 

OMB control number 0910–0078; the 

collections of information in 21 CFR 

part 814, subparts A through E, have 

been approved under OMB control 

number 0910–0231; the collections of 

information in 21 CFR part 814, subpart 

H, have been approved under OMB 

control number 0910–0332; the 

collections of information in 21 CFR 

part 820 have been approved under 

OMB control number 0910–0073; the 

collections of information in 21 CFR 

part 822 have been approved under 

OMB control number 0910–0449; and 

the collections of information regarding 

‘‘Requests for Feedback on Medical 

Device Submissions’’ have been 

approved under OMB control number 

0910–0756. 

Dated: October 20, 2017. 

Leslie Kux, 

Associate Commissioner for Policy. 

[FR Doc. 2017–23195 Filed 10–24–17; 8:45 am] 

BILLING CODE 4164–01–P 

DEPARTMENT OF HEALTH AND 

HUMAN SERVICES 

Food and Drug Administration 

[Docket No. FDA–2011–D–0453] 

Deciding When To Submit a 510(k) for 

a Change to an Existing Device; 

Guidance for Industry and Food and 

Drug Administration Staff; 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 the 

guidance entitled ‘‘Deciding When to 

Submit a 510(k) for a Change to an 

Existing Device.’’ FDA is issuing this 

final guidance document to clarify when 

a change in a legally marketed medical 

device would require that a 

manufacturer submit a premarket 

notification (510(k)) to FDA. This 

guidance document supersedes 

‘‘Deciding When to Submit a 510(k) for 

a Change to an Existing Device,’’ issued 

January 10, 1997. FDA is correcting an 

error in the docket number assigned to 

the ‘‘Deciding When to Submit a 510(k) 

for a Change to an Existing Device’’ 

notice of availability when it published 

in the Federal Register (81 FR 52443, 

August 8, 2016). The docket number 

currently is FDA–2016–D–2021. FDA is 

changing the docket number to FDA– 

2011–D–0453. This action is 

administrative in nature and is being 

taken to avoid any potential confusion 

in the docket. 

DATES: The announcement of the 

guidance is published in the Federal 

Register on October 25, 2017. 

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– 

2011–D–0453 for ‘‘Deciding When to 

Submit a 510(k) for a Change to an 

Existing Device.’’ 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. 


sradovich on DSK3GMQ082PROD with NOTICES