Federal Register / Vol. 86, No. 125 / Friday, July 2, 2021 / Notices 35305 

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– 

2020–D–2323 for ‘‘Assessment of 

Adhesion for Topical and Transdermal 

Systems Submitted in New Drug 

Applications.’’ 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, 240–402–7500. 

• Confidential Submissions—To 

submit a comment with confidential 

information that you do not wish to be 

made publicly available, submit your 

comments only as a written/paper 

submission. You should submit two 

copies total. One copy will include the 

information you claim to be confidential 

with a heading or cover note that states 

‘‘THIS DOCUMENT CONTAINS 

CONFIDENTIAL INFORMATION.’’ The 

Agency will review this copy, including 

the claimed confidential information, in 

its consideration of comments. The 

second copy, which will have the 

claimed confidential information 

redacted/blacked out, will be available 

for public viewing and posted on 

https://www.regulations.gov. Submit 

both copies to the Dockets Management 

Staff. If you do not wish your name and 

contact information to be made publicly 

available, you can provide this 

information on the cover sheet and not 

in the body of your comments and you 

must identify this information as 

‘‘confidential.’’ Any information marked 

as ‘‘confidential’’ will not be disclosed 

except in accordance with 21 CFR 10.20 

and other applicable disclosure law. For 

more information about FDA’s posting 

of comments to public dockets, see 80 

FR 56469, September 18, 2015, or access 

the information at: https://

www.govinfo.gov/content/pkg/FR-2015- 

09-18/pdf/2015-23389.pdf. 

Docket: For access to the docket to 

read background documents or the 

electronic and written/paper comments 

received, go to https://

www.regulations.gov and insert the 

docket number, found in brackets in the 

heading of this document, into the 

‘‘Search’’ box and follow the prompts 

and/or go to the Dockets Management 

Staff, 5630 Fishers Lane, Rm. 1061, 

Rockville, MD 20852, 240–402–7500. 

You may submit comments on any 

guidance at any time (see 21 CFR 

10.115(g)(5)). 

Submit written requests for single 

copies of the draft 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 draft guidance document. 

FOR FURTHER INFORMATION CONTACT: 

Margaret Kober, Center for Drug 

Evaluation and Research (HFD–580), 

Food and Drug Administration, 10903 

New Hampshire Ave., Bldg. 22, Rm. 

5376, Silver Spring, MD 20993–0002, 

301–796–0934. 

SUPPLEMENTARY INFORMATION: 

I. Background 

FDA is announcing the availability of 

a draft guidance for industry entitled 

‘‘Assessment of Adhesion for Topical 

and Transdermal Systems Submitted in 

New Drug Applications.’’ This draft 

guidance provides recommendations on 

the clinical assessment of the adhesive 

properties of topical and transdermal 

delivery systems (collectively referred to 

as TDS) intended for submission in an 

NDA or supplemental NDA. The 

amount of drug delivered into and 

through the patient’s skin from a TDS is 

dependent, in part, on the ability of the 

TDS to remain in direct contact with the 

skin (adhesive properties). Adhesive 

properties are clinically important as a 

loss of TDS adhesion during wear can 

reduce the amount of drug delivered to 

the patient, potentially compromising 

effectiveness. Additionally, partial or 

full detachment of a TDS from a 

patient’s skin may result in 

unintentional exposure of the drug to 

others, potentially compromising safety. 

This draft guidance includes key 

considerations for the design of the TDS 

adhesion clinical study, including the 

selection of endpoints and FDA’s 

current thinking on acceptable adhesion 

performance in the in vivo setting. 

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 ‘‘Assessment of Adhesion for Topical 

and Transdermal Systems Submitted in 

New Drug Applications’’ and will 

supersede in vivo recommendations in 

section V., Special Topics in the draft 

guidance for industry ‘‘Transdermal and 

Topical Delivery Systems—Product 

Development and Quality 

Considerations’’ issued on November 

21, 2019 (84 FR 64319). It does not 

establish any rights for any person and 

is not binding on FDA or the public. 

You can use an alternative approach if 

it satisfies the requirements of the 

applicable statutes and regulations. 

II. Paperwork Reduction Act of 1995 

While this guidance contains no 

collection of information, it does refer to 

previously approved FDA collections of 

information. Therefore, clearance by the 

Office of Management and Budget 

(OMB) under the Paperwork Reduction 

Act of 1995 (PRA) (44 U.S.C. 3501– 

3521) is not required for this guidance. 

The previously approved collections of 

information are subject to review by 

OMB under the PRA. The collections of 

information in 21 CFR part 314 have 

been approved under OMB control 

number 0910–0001, and the collections 

of information for the electronic 

submission of drug establishment 

registration and drug listing information 

have been approved under OMB control 

number 0910–0045. 

III. Electronic Access 

Persons with access to the internet 

may obtain the draft guidance at either 

https://www.fda.gov/drugs/guidancecompliance-regulatory-information/ 

guidances-drugs or https://

www.regulations.gov. 

Dated: June 28, 2021. 

Lauren K. Roth, 

Acting Principal Associate Commissioner for 

Policy. 

[FR Doc. 2021–14202 Filed 7–1–21; 8:45 am] 

BILLING CODE 4164–01–P 

DEPARTMENT OF HEALTH AND 

HUMAN SERVICES 

Food and Drug Administration 

[Docket No. FDA–2020–D–0938] 

Evaluating Cancer Drugs in Patients 

With Central Nervous System 

Metastases; Guidance for Industry; 

Availability 

AGENCY: Food and Drug Administration, 

HHS. 


lotter on DSK11XQN23PROD with NOTICES1
35306 Federal Register / Vol. 86, No. 125 / Friday, July 2, 2021 / Notices 

ACTION: Notice of availability. 

SUMMARY: The Food and Drug 

Administration (FDA or Agency) is 

announcing the availability of a final 

guidance entitled ‘‘Evaluating Cancer 

Drugs in Patients with Central Nervous 

System Metastases; Guidance for 

Industry.’’ The guidance document 

provides recommendations regarding 

the design of clinical trials of drugs and 

biological products regulated by the 

Center for Drug Evaluation and Research 

(CDER) and the Center for Biologics 

Evaluation and Research (CBER) that are 

intended to support product labeling 

describing the antitumor activity in 

patients with central nervous system 

(CNS) metastases from solid tumors 

originating outside the CNS. The 

guidance includes study design 

recommendations regarding the patient 

population, available therapy, prior 

therapies, assessment of CNS disease, 

study endpoints, and leptomeningeal 

disease. The guidance announced in 

this notice finalizes the draft guidance 

of the same title dated August 2020. 

DATES: The announcement of the 

guidance is published in the Federal 

Register on July 2, 2021. 

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– 

2020–D–0938 for ‘‘Evaluating Cancer 

Drugs in Patients with Central Nervous 

System Metastases.’’ 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, 240–402–7500. 

• Confidential Submissions—To 

submit a comment with confidential 

information that you do not wish to be 

made publicly available, submit your 

comments only as a written/paper 

submission. You should submit two 

copies total. One copy will include the 

information you claim to be confidential 

with a heading or cover note that states 

‘‘THIS DOCUMENT CONTAINS 

CONFIDENTIAL INFORMATION.’’ The 

Agency will review this copy, including 

the claimed confidential information, in 

its consideration of comments. The 

second copy, which will have the 

claimed confidential information 

redacted/blacked out, will be available 

for public viewing and posted on 

https://www.regulations.gov. Submit 

both copies to the Dockets Management 

Staff. If you do not wish your name and 

contact information to be made publicly 

available, you can provide this 

information on the cover sheet and not 

in the body of your comments and you 

must identify this information as 

‘‘confidential.’’ Any information marked 

as ‘‘confidential’’ will not be disclosed 

except in accordance with 21 CFR 10.20 

and other applicable disclosure law. For 

more information about FDA’s posting 

of comments to public dockets, see 80 

FR 56469, September 18, 2015, or access 

the information at: https://

www.govinfo.gov/content/pkg/FR-2015- 

09-18/pdf/2015-23389.pdf. 

Docket: For access to the docket to 

read background documents or the 

electronic and written/paper comments 

received, go to https://

www.regulations.gov and insert the 

docket number, found in brackets in the 

heading of this document, into the 

‘‘Search’’ box and follow the prompts 

and/or go to the Dockets Management 

Staff, 5630 Fishers Lane, Rm. 1061, 

Rockville, MD 20852, 240–402–7500. 

You may submit comments on any 

guidance at any time (see 21 CFR 

10.115(g)(5)). 

Submit written requests for single 

copies of the guidance to 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 the 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: 

Shanthi Marur, Center for Drug 

Evaluation and Research, Food and 

Drug Administration, 10903 New 

Hampshire Ave., Bldg. 22, Rm. 2369, 

Silver Spring, MD 20993–0002, 240– 

402–6373; 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 announcing the availability of 

a document entitled ‘‘Evaluating Cancer 

Drugs in Patients with Central Nervous 

System Metastases.’’ This guidance 

provides recommendations for sponsors 

designing clinical trials of drugs and 

biological products regulated by CDER 

and CBER that are intended to support 

product labeling describing the 

antitumor activity in patients with CNS 

metastases from solid tumors originating 

outside the CNS. Specifically, the 

guidance includes recommendations 

regarding the patient population, 

available therapy, prior therapies, 

assessment of CNS disease, study 

endpoints, and leptomeningeal disease. 

The guidance describes that CNS 

metastases should be evaluated in the 

context of the entire disease burden and 

discusses how treatment effects may be 

described in drug labeling. The 

recommendations pertain to clinical 

trials for systemic anticancer drugs 

where patients with CNS metastases are 

included in the study population. These 

recommendations are also applicable to 


lotter on DSK11XQN23PROD with NOTICES1
Federal Register / Vol. 86, No. 125 / Friday, July 2, 2021 / Notices 35307 

trials conducted exclusively in patients 

with CNS metastases. 

CNS metastases are associated with 

significant morbidity and mortality and 

development of therapeutic products for 

patients with CNS metastases is needed. 

FDA has participated in efforts to 

facilitate drug development for patients 

with CNS metastases, including a March 

2019 ‘‘Workshop on Product 

Development for CNS Metastases.’’ 

Stakeholders at this meeting stated there 

is a need for further FDA guidance on 

specific topics, including identifying 

optimal study endpoints. Study design 

challenges for CNS metastases include 

uncertainty regarding optimal 

endpoints, lack of standardized 

response assessments, understanding 

how CNS metastases are evaluated in 

the context of the entire burden of 

metastatic disease to characterize a 

drug’s potential benefit (e.g., timing of 

CNS radiographic assessments relative 

to other sites of metastases), and 

interpreting radiographic response in 

the setting of recent radiation therapy or 

surgery. This guidance is intended to 

provide recommendations on these 

study design challenges. 

In the Federal Register of August 27, 

2020 (85 FR 53007), FDA announced the 

availability of the draft guidance 

‘‘Evaluating Cancer Drugs in Patients 

with Central Nervous System 

Metastases’’ dated August 2020. FDA 

received several comments on the draft 

guidance and those comments were 

considered as the guidance was 

finalized. A summary of changes 

includes: Clarification on the number of 

stratification factors the protocol should 

specify in order to minimize bias, 

confirmation of the version of Response 

Evaluation Criteria in Solid Tumours 

(RECIST) that should be referred to 

when evaluating CNS disease, 

clarification that both CNS and 

systematic duration of response should 

be captured and the addition of a 6- 

month timepoint, and the addition of 

progression-free survival in patients 

with brain metastasis as another 

measurement to be reported when CNS 

is a common metastatic site. In addition, 

editorial changes were made to improve 

clarity. The guidance announced in this 

notice finalizes the draft guidance dated 

August 27, 2020. 

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 ‘‘Evaluating Cancer 

Drugs in Patients with Central Nervous 

System Metastases.’’ It does not 

establish any rights for any person and 

is not binding on FDA or the public. 

You can use an alternative approach if 

it satisfies the requirements of the 

applicable statutes and regulations. 

II. Paperwork Reduction Act of 1995 

While this guidance contains no 

collection of information, it does refer to 

previously approved FDA collections of 

information. Therefore, clearance by the 

Office of Management and Budget 

(OMB) under the Paperwork Reduction 

Act of 1995 (PRA) (44 U.S.C. 3501– 

3521) is not required for this guidance. 

The previously approved collections of 

information are subject to review by 

OMB under the PRA. The collections of 

information in 21 CFR part 312 have 

been approved under OMB control 

number 0910–0014; the collections of 

information in 21 CFR part 314 have 

been approved under OMB control 

number 0910–0001; the collections of 

information in 21 CFR part 601 have 

been approved under 0910–0338; and 

the collections of information in 21 CFR 

201.56 and 201.57 have been approved 

under OMB control number 0910–0572. 

III. Electronic Access 

Persons with access to the internet 

may obtain the guidance at either 

https://www.fda.gov/vaccines-bloodbiologics/guidance-complianceregulatory-information-biologics/ 

biologics-guidances or https://

www.regulations.gov. 

Dated: June 28, 2021. 

Lauren K. Roth, 

Acting Principal Associate Commissioner for 

Policy. 

[FR Doc. 2021–14194 Filed 7–1–21; 8:45 am] 

BILLING CODE 4164–01–P 

DEPARTMENT OF HEALTH AND 

HUMAN SERVICES 

Food and Drug Administration 

[Docket No. FDA–2020–N–0026] 

Issuance of Priority Review Voucher; 

Rare Pediatric Disease Product 

AGENCY: Food and Drug Administration, 

HHS. 

ACTION: Notice. 

SUMMARY: The Food and Drug 

Administration (FDA) is announcing the 

issuance of a priority review voucher to 

the sponsor of a rare pediatric disease 

product application. The Federal Food, 

Drug, and Cosmetic Act (FD&C Act) 

authorizes FDA to award priority review 

vouchers to sponsors of approved rare 

pediatric disease product applications 

that meet certain criteria. FDA is 

required to publish notice of the award 

of the priority review voucher. FDA has 

determined that RYPLAZIM 

(plasminogen, human-tvmh), 

manufactured by Prometic 

Bioproduction, Inc., meets the criteria 

for a priority review voucher. 

FOR FURTHER INFORMATION CONTACT: 

Myrna Hanna, 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: FDA is 

announcing the issuance of a priority 

review voucher to the sponsor of an 

approved rare pediatric disease product 

application. Under section 529 of the 

FD&C Act (21 U.S.C. 360ff), FDA will 

award priority review vouchers to 

sponsors of approved rare pediatric 

disease product applications that meet 

certain criteria. FDA has determined 

that RYPLAZIM (plasminogen, humantvmh), manufactured by Prometic 

Bioproduction, Inc., meets the criteria 

for a priority review voucher. 

RYPLAZIM (plasminogen, human-tvmh) 

is indicated for the treatment of patients 

with plasminogen deficiency type 1 

(hypoplasminogenemia). 

For further information about the Rare 

Pediatric Disease Priority Review 

Voucher Program and for a link to the 

full text of section 529 of the FD&C Act, 

go to https://www.fda.gov/industry/ 

developing-products-rare-diseasesconditions/rare-pediatric-disease-rpddesignation-and-voucher-programs. For 

further information about RYPLAZIM 

(plasminogen, human-tvmh), go to the 

Center for Biologics Evaluation and 

Research Cellular and Gene Therapy 

Products website at https://

www.fda.gov/vaccines-blood-biologics/ 

cellular-gene-therapy-products/ 

approved-cellular-and-gene-therapyproducts. 

Dated: June 25, 2021. 

Lauren K. Roth, 

Acting Principal Associate Commissioner for 

Policy. 

[FR Doc. 2021–14191 Filed 7–1–21; 8:45 am] 

BILLING CODE 4164–01–P 

DEPARTMENT OF HEALTH AND 

HUMAN SERVICES 

National Institutes of Health 

National Institute of Allergy and 

Infectious Diseases; Notice of Closed 

Meeting 

Pursuant to section 10(d) of the 

Federal Advisory Committee Act, as 

amended, notice is hereby given of the 

following meeting. 

The meeting will be closed to the 

public in accordance with the 


lotter on DSK11XQN23PROD with NOTICES1