44884 Federal Register / Vol. 83, No. 171 / Tuesday, September 4, 2018 / Notices 

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)). 

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. Send one self-addressed adhesive 

label to assist that office in processing 

your requests. See the SUPPLEMENTARY

INFORMATION section for electronic 

access to the guidance document. 

FOR FURTHER INFORMATION CONTACT: 

Xinyuan Zhang, Office of Clinical 

Pharmacology, Office of Translational 

Sciences, Center for Drug Evaluation 

and Research, Food and Drug 

Administration, 10903 New Hampshire 

Ave., Bldg. 51, Rm. 2128, Silver Spring, 

MD 20993–0002, 240–402–7971. 

SUPPLEMENTARY INFORMATION: 

I. Background 

FDA is announcing the availability of 

a final guidance for industry entitled 

‘‘Physiologically Based Pharmacokinetic 

Analyses—Format and Content.’’ A 

PBPK analysis uses models and 

simulations that combine physiology, 

population, and drug characteristics to 

mechanistically describe the 

pharmacokinetic behaviors of a drug or 

drug product. Throughout a drug’s life 

cycle, PBPK model predictions can be 

used to support decisions on whether, 

when, and how to conduct certain 

clinical pharmacology studies, and to 

support dosing recommendations in 

product labeling. Because of the lack of 

regulatory guidance, the format and 

content of PBPK analysis reports that 

are submitted to FDA vary significantly. 

The goal of this guidance is to 

standardize the content and format of 

these reports to facilitate FDA’s efficient 

assessment, consistent application, and 

timely decision making during 

regulatory review. 

This guidance outlines the 

recommended format and content for a 

sponsor or applicant to submit PBPK 

analyses to FDA to support applications 

including, but not limited to, INDs, 

NDAs, BLAs, and ANDAs. This 

guidance does not address 

methodological considerations and best 

practices for the conduct of PBPK 

modeling and simulation or the 

appropriateness of PBPK analyses for a 

particular drug or a drug product. 

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 ‘‘Physiologically 

Based Pharmacokinetic Analyses— 

Format and Content.’’ 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. 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 collection of information in 

21 CFR 314.50(d) has been approved 

under OMB control number 0910–0001. 

III. Electronic Access 

Persons with access to the internet 

may obtain the guidance at either 

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

ComplianceRegulatoryInformation/ 

Guidances/default.htm or https://

www.regulations.gov. 

Dated: August 27, 2018. 

Leslie Kux, 

Associate Commissioner for Policy. 

[FR Doc. 2018–19065 Filed 8–31–18; 8:45 am] 

BILLING CODE 4164–01–P 

DEPARTMENT OF HEALTH AND 

HUMAN SERVICES 

Food and Drug Administration 

[Docket No. FDA–2014–N–1048] 

Agency Information Collection 

Activities; Submission for Office of 

Management and Budget Review; 

Comment Request; Medical Device 

Labeling Regulations 

AGENCY: Food and Drug Administration, 

HHS. 

ACTION: Notice. 

SUMMARY: The Food and Drug 

Administration (FDA) is announcing 

that a proposed collection of 

information has been submitted to the 

Office of Management and Budget 

(OMB) for review and clearance under 

the Paperwork Reduction Act of 1995. 

DATES: Fax written comments on the 

collection of information by October 4, 

2018. 

ADDRESSES: To ensure that comments on 

the information collection are received, 

OMB recommends that written 

comments be faxed to the Office of 

Information and Regulatory Affairs, 

OMB, Attn: FDA Desk Officer, Fax: 202– 

395–7285, or emailed to oira_

submission@omb.eop.gov. All 

comments should be identified with the 

OMB control number 0910–0485. Also 

include the FDA docket number found 

in brackets in the heading of this 

document. 

FOR FURTHER INFORMATION CONTACT: 

Amber Sanford, Office of Operations, 

Food and Drug Administration, Three 

White Flint North, 10A–12M, 11601 

Landsdown St., North Bethesda, MD 

20852, 301–796–8867, PRAStaff@

fda.hhs.gov. 

SUPPLEMENTARY INFORMATION: In 

compliance with 44 U.S.C. 3507, FDA 

has submitted the following proposed 

collection of information to OMB for 

review and clearance. 

Medical Device Labeling Regulations— 

21 CFR Parts 800, 801, and 809 

OMB Control Number 0910–0485— 

Extension 

Section 502 of the Federal Food, Drug, 

and Cosmetic Act (FD&C Act) (21 U.S.C. 

352), among other things, establishes 

requirements for the label or labeling of 

a medical device so that it is not 

misbranded and subject to a regulatory 

action. Certain provisions under section 

502 of the FD&C Act require 

manufacturers, importers, and 

distributors of medical devices to 

disclose information about themselves 

or the devices on the labels or labeling 

for the devices. 

Section 502(b) of the FD&C Act 

requires that for packaged devices, the 

label must bear the name and place of 

business of the manufacturer, packer, or 

distributor; and an accurate statement of 

the quantity of the contents. Section 

502(f) of the FD&C Act requires that the 

labeling for a device must contain 

adequate directions for use. FDA may, 

however, grant an exemption if the 

Agency determines that the adequate 

directions for use labeling requirements 

are not necessary for the particular case 

as it relates to protection of the public 

health. 

FDA regulations under parts 800, 801, 

and 809 (21 CFR parts 800, 801, and 

809) require disclosure of specific 


sradovich on DSK3GMQ082PROD with NOTICES
Federal Register / Vol. 83, No. 171 / Tuesday, September 4, 2018 / Notices 44885 

information by manufacturers, 

importers, and distributors of medical 

devices about themselves or the devices, 

on the label or labeling for the devices, 

to health professionals and consumers. 

Most of the regulations under parts 800, 

801, and 809 are derived from 

requirements of section 502 of the FD&C 

Act. Section 502 provides, in part, that 

a device shall be misbranded if, among 

other things, its label or labeling fails to 

bear certain required information 

concerning the device, is false or 

misleading in any particular way, or 

fails to contain adequate directions for 

use. 

Recordkeeping Burden 

Section 801.150(a)(2) establishes 

recordkeeping requirements for 

manufacturers of devices to retain a 

copy of the agreement containing the 

specifications for the processing, 

labeling, or repacking of the device for 

2 years after the final shipment or 

delivery of the device. Section 

801.150(a)(2) also requires that the 

subject respondents make copies of this 

agreement available for inspection at 

any reasonable hour to any officer or 

employee of the Department of Health 

and Human Services (HHS) who 

requests them. 

Section 801.410(e) requires copies of 

invoices, shipping documents, and 

records of sale or distribution of all 

impact resistant lenses, including 

finished eyeglasses and sunglasses, be 

maintained for 3 years by the retailer 

and made available upon request by any 

officer or employee of FDA or by any 

other officer or employee acting on 

behalf of the Secretary of HHS. 

Section 801.410(f) requires that the 

results of impact tests and description of 

the test method and apparatus be 

retained for a period of 3 years. 

Section 801.421(d) establishes 

requirements for hearing aid dispensers 

to retain copies of all physician 

statements or any waivers of medical 

evaluation for 3 years after dispensing 

the hearing aid. 

Section 801.430(f) requires 

manufacturers of menstrual tampons to 

devise and follow an ongoing sampling 

plan for measuring the absorbency of 

menstrual tampons. In addition, 

manufacturers must use the method and 

testing parameters described in 

§ 801.430(f). 

Section 801.435(g) requires latex 

condom manufacturers to document and 

provide, upon request, an appropriate 

justification for the application of the 

testing data from one product on any 

variation of that product to support 

expiration dating in the user labeling. 

Third-Party Disclosure Burden 

Sections 800.10(a)(3) and 800.12(c) 

require that the label for contact lens 

cleaning solutions bear a prominent 

statement alerting consumers of the 

tamper-resistant feature. Further, 

§ 800.12 requires that packaged contact 

lens cleaning solutions contain a 

tamper-resistant feature to prevent 

malicious adulteration. 

Section 800.10(b)(2) requires that the 

labeling for liquid ophthalmic 

preparations packed in multiple-dose 

containers provide information on the 

duration of use and the necessary 

warning information to afford adequate 

protection from contamination during 

use. 

Section 801.1 requires that the label 

for a device in package form contain the 

name and place of business of the 

manufacturer, packer, or distributor. 

Section 801.5 requires that labeling 

for a device include information on 

intended use as defined under § 801.4 

and provide adequate directions to 

assure safe use by the lay consumers. 

Section 801.61 requires that the 

principal display panel of an over-thecounter (OTC) device in package form 

must bear a statement of the identity of 

the device. The statement of identity of 

the device must include the common 

name of the device followed by an 

accurate statement of the principal 

intended actions of the device. Section 

801.62 requires that the label for an OTC 

device in package form shall bear a 

declaration of the net quantity of 

contents. The label must express the net 

quantity in terms of weight, measure, 

numerical count, or a combination of 

numerical count and weight, measure, 

or size. 

Section 801.109 establishes labeling 

requirements for prescription devices, 

in which the label for the device must 

describe the application or use of the 

device and contain a cautionary 

statement restricting the device for sale 

by, or on the order of, an appropriate 

professional. 

Section 801.110 establishes labeling 

requirements for a prescription device 

delivered to the ultimate purchaser or 

user, by a licensed practitioner. The 

device must be accompanied by labeling 

bearing the name and address of the 

licensed practitioner, directions for use, 

and cautionary statements, if any, 

provided by the order. 

Section 801.150(e) requires a written 

agreement between firms involved in 

the assembling or packaging of a 

nonsterile device containing labeling 

that identifies the final finished device 

as sterile and then shipping such device 

in interstate commerce prior to 

sterilization. In addition, § 801.150(e) 

requires that each pallet, carton, or other 

designated unit be conspicuously 

marked to show its nonsterile nature 

when introduced into interstate 

commerce and while being held prior to 

sterilization. When both requirements 

are met, FDA will take no regulatory 

action against the device as being 

misbranded or adulterated. 

Section 801.405(b)(1) provides for 

labeling requirements for articles, 

including repair kits, re-liners, pads, 

and cushions, intended for use in 

temporary repairs and refitting of 

dentures for lay persons. Section 

801.405(b)(1) also requires that the 

labeling contain the word ‘‘emergency’’ 

preceding and modifying each 

indication-for-use statement for denture 

repair kits, and the word ‘‘temporary’’ 

preceding and modifying each 

indication-for-use statement for reliners, pads, and cushions. 

Section 801.405(c) provides for 

labeling requirements that contain 

essentially the same information 

described under § 801.405(b)(1). The 

information is intended to enable a lay 

person to understand the limitations of 

using OTC denture repair kits and 

denture re-liners, pads, and cushions. 

Section 801.420(c)(1) requires that 

manufacturers or distributors of hearing 

aids develop a user instructional 

brochure to be provided by the 

dispenser of the hearing aid to 

prospective users. The brochure must 

contain detailed information on the use 

and maintenance of the hearing aid. 

Section 801.420(c)(4) establishes 

requirements that the user instructional 

brochure or separate labeling provide 

for technical data elements useful for 

selecting, fitting, and checking the 

performance of a hearing aid. In 

addition, § 801.420(c)(4) provides for 

testing requirements to determine that 

the required data elements must be 

conducted in accordance with the 

American National Standards Institute 

(ANSI) ‘‘Specification of Hearing Aid 

Characteristics,’’ ANSI S3.22–2003 

(Revision of ANSI S3.22–1996), which 

is incorporated by reference in 

accordance with 5 U.S.C. 552(a) and 1 

CFR part 51. 

Section 801.421(b) establishes 

requirements for the hearing aid 

dispenser to provide prospective users 

with a copy of the user instructional 

brochure along with an opportunity to 

review content, either orally or by the 

predominant method of communication 

used during the sale. 

Section 801.421(c) establishes 

requirements for the hearing aid 

dispenser to provide a copy of the user 

instructional brochure to the 


sradovich on DSK3GMQ082PROD with NOTICES
44886 Federal Register / Vol. 83, No. 171 / Tuesday, September 4, 2018 / Notices 

prospective purchaser of any hearing 

aid upon request, or, if the brochure is 

unavailable, provide the name and 

address of the manufacturer or 

distributor from which it may be 

obtained. 

Section 801.430(d) establishes 

labeling requirements for menstrual 

tampons to provide information on 

signs, risk factors, and ways to reduce 

the risk of Toxic Shock Syndrome 

(TSS). 

Section 801.430(e)(2) requires 

menstrual tampon package labels to 

provide information on the ranges of 

absorbency and absorbency term based 

on testing required under § 801.430(f) 

and an explanation of selecting 

absorbencies that reduce the risk of 

contracting TSS. 

Section 801.435(b), (c), and (h) 

establishes requirements for condom 

labeling to bear an expiration date that 

is supported by testing that 

demonstrates the integrity of three 

random lots of the product. 

Section 809.10(a) and (b) establishes 

requirements that a label for an in vitro 

diagnostic (IVD) device and the 

accompanying labeling (package insert) 

must contain information identifying its 

intended use, instructions for use, lot or 

control number, and source. 

Section 809.10(d) provides that the 

labeling requirements for general 

purpose laboratory reagents may be 

exempt from the requirements of 

§ 809.10(a) and (b) if the labeling 

contains information to include, 

identifying its intended use, 

instructions for use, lot or control 

number, and source. 

Section 809.10(e) provides that the 

labeling for analyte specific reagents 

(ASRs) shall provide information to 

include, identifying the quantity, 

proportion, or concentration of each 

reagent ingredient, instructions for use, 

lot or control number, and source. 

Section 809.10(f) provides that the 

labeling for OTC test sample collection 

systems for drugs of abuse shall include, 

among other things, information on the 

intended use, specimen collection 

instructions, identification system, and 

information about use of the test results. 

Section 809.30(d) requires that 

advertising and promotional materials 

for ASRs include the identity and purity 

of the ASR and the identity of the 

analyte. 

Section 1040.20(d) (21 CFR 1040.20) 

provides that manufacturers of sunlamp 

products and ultraviolet lamps are 

subject to the labeling regulations under 

part 801. 

The burden estimates are based on 

FDA’s current registration and listing 

data and shipment information. 

In the Federal Register of February 

22, 2018 (83 FR 7728), FDA published 

a 60-day notice requesting public 

comment on the proposed collection of 

information. FDA received one 

comment regarding environmental 

concerns. We believe this issue is 

beyond the scope of this information 

request. 

FDA estimates the burden of this 

collection of information as follows: 

TABLE 1—ESTIMATED ANNUAL RECORDKEEPING BURDEN 1

Activity/21 CFR section Number of 

recordkeepers 

Number of 

records per 

recordkeeper 

Total 

annual 

records 

Average 

burden per 

recordkeeping 

Total 

hours 

Processing, labeling, or repacking agreement— 

801.150(a)(2).

6,331 887 5,615,597 .5 (30 minutes) ............ 2,807,799 

Impact resistant lenses; invoices, shipping documents, and records of sale or distribution— 

801.410(e) and (f).

1,119 47,050 52,648,950 0.0008 (.05 minutes) ... 42,119 

Hearing aid records—801.421(d) ........................... 10,000 160 1,600,000 .25 (15 minutes) .......... 400,000 

Menstrual tampons, sampling plan for measuring 

absorbency—801.430(f).

16 11 176 80 ................................ 14,080 

Latex condoms; justification for the application of 

testing data to the variation of the tested product—801.435(g).

51 3.65 186 1 .................................. 186 

Total ................................................................ ........................ ........................ ........................ ..................................... 3,264,184 

1There are no capital costs or operating and maintenance costs associated with this collection of information. 

TABLE 2—ESTIMATED ANNUAL THIRD-PARTY DISCLOSURE BURDEN 1

Activity/21 CFR section Number of 

respondents 

Number of 

disclosures 

per 

respondent 

Total 

annual 

disclosures 

Average 

burden per 

disclosure 

Total 

hours 

Contact lens cleaning solution labeling— 

800.10(a)(3) and 800.12(c).

25 8 200 1 .................................. 200 

Liquid ophthalmic preparation labeling— 

800.10(b)(2).

25 8 200 1 .................................. 200 

Manufacturer, packer, or distributor information— 

801.1.

18,137 7 126,959 1 .................................. 126,959 

Adequate directions for use—801.5 ...................... 8,526 6 51,156 22.35 ........................... 1,143,337 

Statement of identify—801.61 ................................ 8,526 6 51,156 1 .................................. 51,156 

Declaration of net quantity of contents—801.62 ... 8,526 6 51,156 1 .................................. 51,156 

Prescription device labeling—801.109 ................... 9,681 6 58,086 17.77 ........................... 1,032,188 

Retail exemption for prescription devices— 

801.110.

30,000 667 20,010,000 .25 (15 minutes) .......... 5,002,500 

Processing, labeling, or repacking; non-sterile devices—801.150(e).453 34 15,402 4 .................................. 61,608 


sradovich on DSK3GMQ082PROD with NOTICES
Federal Register / Vol. 83, No. 171 / Tuesday, September 4, 2018 / Notices 44887 

TABLE 2—ESTIMATED ANNUAL THIRD-PARTY DISCLOSURE BURDEN 1—Continued 

Activity/21 CFR section Number of 

respondents 

Number of 

disclosures 

per 

respondent 

Total 

annual 

disclosures 

Average 

burden per 

disclosure 

Total 

hours 

Labeling of articles intended for lay use in the repairing and/or refitting of dentures— 

801.405(b)(1).

35 1 35 4 .................................. 140 

Dentures; information regarding temporary and 

emergency use—801.405(c).

35 1 35 4 .................................. 140 

Labeling requirements for hearing aids— 

801.420(c)(1).

124 12 1,488 40 ................................ 59,520 

Technical data for hearing aids—801.420(c)(4) .... 124 12 1,488 80 ................................ 119,040 

Hearing aids, opportunity to review User Instructional Brochure—801.421(b).10,000 160 1,600,000 .30 (20 minutes) .......... 480,000 

Hearing aids, availability of User Instructional Brochure—801.421(c).10,000 5 50,000 .17 ...............................

(10 minutes) ................

8,500 

User labeling for menstrual tampons—801.430(d) 16 8 128 2 .................................. 256 

Menstrual tampons, ranges of absorbency— 

801.430(e)(2).

16 8 128 2 .................................. 256 

User labeling for latex condoms—801.435(b), (c), 

and (h).

51 6 306 100 .............................. 30,600 

Labeling for IVDs—809.10(a) and (b) .................... 1,700 6 10,200 80 ................................ 816,000 

Labeling for general purpose laboratory reagents—809.10(d)(1).300 2 600 40 ................................ 24,000 

Labeling for ASRs—809.10(e) ............................... 300 25 7,500 1 .................................. 7,500 

Labeling for OTC test sample collection systems 

for drugs of abuse testing—809.10(f).

20 1 20 100 .............................. 2,000 

Advertising and promotional materials for ASRs— 

809.30(d).

300 25 7,500 1 .................................. 7,500 

Labeling of sunlamp products—1040.20(d) ........... 19 1 19 10 ................................ 190 

Total ................................................................ ........................ ........................ ........................ ..................................... 9,024,946 

1There are no capital costs or operating and maintenance costs associated with this collection of information. 

The number of recordkeepers/ 

respondents and records/disclosures has 

been adjusted to reflect updated Agency 

data. These adjustments result in an 

increase of 1,598,48 hours since the last 

OMB approval. 

Dated: August 28, 2018. 

Leslie Kux, 

Associate Commissioner for Policy. 

[FR Doc. 2018–19086 Filed 8–31–18; 8:45 am] 

BILLING CODE 4164–01–P 

DEPARTMENT OF HEALTH AND 

HUMAN SERVICES 

Food and Drug Administration 

[Docket No. FDA–2018–N–3091] 

Advisory Committee; Cardiovascular 

and Renal Drugs Advisory Committee; 

Renewal 

AGENCY: Food and Drug Administration, 

HHS. 

ACTION: Notice; renewal of advisory 

committee. 

SUMMARY: The Food and Drug 

Administration (FDA) is announcing the 

renewal of the Cardiovascular and Renal 

Drugs Advisory Committee by the 

Commissioner of Food and Drugs (the 

Commissioner). The Commissioner has 

determined that it is in the public 

interest to renew the Cardiovascular and 

Renal Drugs Advisory Committee for an 

additional 2 years beyond the charter 

expiration date. The new charter will be 

in effect until August 27, 2020. 

DATES: Authority for the Cardiovascular 

and Renal Drugs Advisory Committee 

will expire on August 27, 2020, unless 

the Commissioner formally determines 

that renewal is in the public interest. 

FOR FURTHER INFORMATION CONTACT: 

Jennifer Shepherd, Center for Drug 

Evaluation and Research, Food and 

Drug Administration, 10903 New 

Hampshire Ave., Bldg. 31, Rm. 2417, 

Silver Spring, MD 20993–0002, 301– 

796–9001, email: CRDAC@fda.hhs.gov. 

SUPPLEMENTARY INFORMATION: Pursuant 

to 41 CFR 102–3.65 and approval by the 

Department of Health and Human 

Services pursuant to 45 CFR part 11 and 

by the General Services Administration, 

FDA is announcing the renewal of the 

Cardiovascular and Renal Drugs 

Advisory Committee. The committee is 

a discretionary Federal advisory 

committee established to provide advice 

to the Commissioner. 

The Cardiovascular and Renal Drugs 

Advisory Committee advises the 

Commissioner or designee in 

discharging responsibilities as they 

relate to helping to ensure safe and 

effective drugs for human use and, as 

required, any other product for which 

FDA has regulatory responsibility. 

The committee reviews and evaluates 

available data concerning the safety and 

effectiveness of marketed and 

investigational human drug products for 

use in the treatment of cardiovascular 

and renal disorders and makes 

appropriate recommendations to the 

Commissioner. 

The committee shall consist of a core 

of 11 voting members including the 

Chair. Members and the Chair are 

selected by the Commissioner or 

designee from among authorities 

knowledgeable in the fields of 

cardiology, hypertension, arrhythmia, 

angina, congestive heart failure, 

diuresis, and biostatistics. Members will 

be invited to serve for overlapping terms 

of up to 4 years. Almost all non-Federal 

members of this committee serve as 

Special Government Employees. The 

core of voting members may include one 

technically qualified member, selected 

by the Commissioner or designee, who 

is identified with consumer interests 

and is recommended by either a 

consortium of consumer-oriented 

organizations or other interested 

persons. In addition to the voting 

members, the committee may include 


sradovich on DSK3GMQ082PROD with NOTICES