Federal Register / Vol. 86, No. 150 / Monday, August 9, 2021 / Notices 43551 

investigation by a State agency of 

complaints relating to compounded 

drug products distributed outside such 

State; or (2) if the drug product is 

compounded in a State that has not 

entered into such an MOU, the licensed 

pharmacist, pharmacy, or physician 

does not distribute, or cause to be 

distributed, compounded drug products 

out of the State in which they are 

compounded in quantities that exceed 5 

percent of the total prescription orders 

dispensed or distributed by such 

pharmacy or physician (statutory 5 

percent limit) (see section 

503A(b)(3)(B)(i) and (ii) of the FD&C 

Act). 

In the Federal Register of October 27, 

2020 (85 FR 68074), FDA announced the 

availability of the final standard MOU 

describing the responsibilities of a State 

Board of Pharmacy or other appropriate 

State agency that chooses to sign the 

final standard MOU in investigating and 

responding to complaints related to 

drug products compounded in such 

State and distributed outside such State 

and in addressing the interstate 

distribution of inordinate amounts of 

compounded human drug products. 

In the October 27, 2020, Federal 

Register notice, FDA stated that it was 

providing a 365-day period for States to 

decide whether to sign the final 

standard MOU before FDA intended to 

begin enforcing the statutory 5 percent 

limit in States that do not sign the final 

standard MOU. Based on comments 

from stakeholders, it was FDA’s 

understanding that this timeframe 

corresponds to a full legislative cycle for 

most States and would, therefore, afford 

sufficient time for States to modify their 

laws and regulations, if necessary in 

order to enter into the final standard 

MOU. 

Following publication of October 27, 

2020, Federal Register notice, FDA 

received requests to extend the period 

before FDA intends to begin enforcing 

the statutory 5 percent limit in States 

that do not sign. The requesters asserted 

that the time period of 365 days was 

insufficient to allow State governments 

to thoroughly evaluate the final 

standard MOU and modify their laws 

and regulations, if necessary in order to 

sign, because many State governments 

were focused on addressing concerns 

raised by the Coronavirus Disease 2019 

(COVID–19) pandemic. 

FDA has considered the requests and 

other relevant factors and is extending 

the period before FDA intends to begin 

enforcing the statutory 5 percent limit in 

States that do not sign the final standard 

MOU until October 27, 2022. FDA 

believes that an additional 1 year will 

allow sufficient time for States to 

consider the final standard MOU and 

modify their laws and regulations, if 

necessary. FDA’s understanding is that 

emergency pandemic response activities 

have now begun to ease, permitting 

States more time to take up other issues. 

Accordingly, we believe a 1-year 

extension addresses the need that some 

States have expressed for additional 

time, without adding significant delay 

to FDA’s implementation of the 

important public health protections 

afforded by section 503A(b)(3)(B) of the 

FD&C Act. 

States may sign the final standard 

MOU at any time, including after the 

period is scheduled to end on October 

27, 2022. 

Dated: August 4, 2021. 

Lauren K. Roth, 

Acting Principal Associate Commissioner for 

Policy. 

[FR Doc. 2021–16937 Filed 8–6–21; 8:45 am] 

BILLING CODE 4164–01–P 

DEPARTMENT OF HEALTH AND 

HUMAN SERVICES 

Food and Drug Administration 

[Docket No. FDA–2018–D–3931] 

Nonmetastatic Castration-Resistant 

Prostate Cancer: Considerations for 

Metastasis-Free Survival Endpoint in 

Clinical Trials; Guidance for Industry; 

Availability 

AGENCY: Food and Drug Administration, 

HHS. 

ACTION: Notice of availability. 

SUMMARY: The Food and Drug 

Administration (FDA or Agency) is 

announcing the availability of a final 

guidance for industry entitled 

‘‘Nonmetastatic Castration-Resistant 

Prostate Cancer: Considerations for 

Metastasis-Free Survival Endpoint in 

Clinical Trials.’’ Recent approvals of 

several drug products for patients with 

nonmetastatic castration-resistant 

prostate cancer have been supported by 

randomized clinical trials 

demonstrating improvements in 

metastasis-free survival. This guidance 

intends to inform potential future 

applicants regarding the Agency’s 

expectations for collection, analysis, 

and reporting of data pertaining to 

metastasis-free survival. This guidance 

finalizes the draft guidance of the same 

title issued on November 14, 2018. 

DATES: The announcement of the 

guidance is published in the Federal 

Register on August 9, 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– 

2018–D–3931 for ‘‘Nonmetastatic 

Castration-Resistant Prostate Cancer: 

Considerations for Metastasis-Free 

Survival Endpoint in Clinical Trials.’’ 

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 


lotter on DSK11XQN23PROD with NOTICES1
43552 Federal Register / Vol. 86, No. 150 / Monday, August 9, 2021 / Notices 

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 this guidance to the Division 

of Drug Information, Center for Drug 

Evaluation and Research, Food and 

Drug Administration, 10001 New 

Hampshire Ave., Hillandale Building, 

4th Floor, Silver Spring, MD 20993– 

0002; or the Office of Communication, 

Outreach, and Development, Center for 

Biologics Evaluation and Research, 

Food and Drug Administration, 10903 

New Hampshire Ave., Bldg. 71, Rm. 

3128, Silver Spring, MD 20993–0002. 

Send one self-addressed adhesive label 

to assist that office in processing your 

requests. See the SUPPLEMENTARY

INFORMATION section for electronic 

access to the guidance document. 

FOR FURTHER INFORMATION CONTACT: Julia 

Beaver, Center for Drug Evaluation and 

Research, Food and Drug 

Administration, 10903 New Hampshire 

Ave., Bldg. 22, Rm. 2100, Silver Spring, 

MD 20993–0002, 240–402–0489; or 

Stephen Ripley, Center for Biologics 

Evaluation and Research, Food and 

Drug Administration, 10903 New 

Hampshire Ave., Bldg. 71, Rm 7268, 

Silver Spring, MD 20993–0002, 240– 

402–7911. 

SUPPLEMENTARY INFORMATION: 

I. Background 

FDA is announcing the availability of 

a final guidance for industry entitled 

‘‘Nonmetastatic Castration-Resistant 

Prostate Cancer: Considerations for 

Metastasis-Free Survival Endpoint in 

Clinical Trials.’’ Nonmetastatic 

castration-resistant prostate cancer 

(nmCRPC) is defined by rising prostatespecific antigen (PSA) despite castrate 

levels of testosterone and no 

radiographic evidence of distant 

metastatic disease. Despite earlier 

detection of localized prostate cancer 

and advances in surgical and radiation 

techniques, many patients will continue 

to have rising PSA after local therapy 

(e.g., surgery, radiation) for recurrent 

disease and subsequent androgen 

deprivation therapy. Patients with 

nmCRPC can have a prolonged disease 

course following the detection of a 

rising PSA until documentation of 

distant metastases or death. Such a 

prolonged assessment period (in which 

patients may receive multiple therapies) 

with low death rates may make the use 

of overall survival impractical as a 

primary endpoint to support approval of 

products in this disease setting. 

These issues were discussed at an 

Oncologic Drugs Advisory Committee 

meeting in 2011, during which the 

committee acknowledged that endpoints 

that can be measured earlier in the 

course of disease, such as metastasisfree survival, defined as the time from 

randomization to distant radiographic 

disease or death, would be useful in 

assessing the treatment effect of 

products in patients with nmCRPC. 

Additionally, the Oncologic Drugs 

Advisory Committee noted that the 

transition from nmCRPC to 

radiographically detectable metastatic 

disease (e.g., bone disease or visceral 

disease) is a clinically relevant event 

that can be associated with morbidity 

and the need for additional medical 

interventions. Conversely, local 

progression events may be treated with 

local therapies, may never progress to 

distant disease, and may not lead to 

systemic morbidity. Thus, a large 

treatment effect on metastasis-free 

survival with an acceptable safety 

profile could demonstrate clinical 

benefit and support product approval. 

This guidance finalizes the draft 

guidance of the same title issued on 

November 14, 2018, (83 FR 56857). 

Changes from the draft to the final 

include clarifying edits and expanding 

upon certain recommendations in the 

draft guidance. 

This guidance is being issued 

consistent with FDA’s good guidance 

practices regulation (21 CFR 10.115). 

The guidance represents the current 

thinking of FDA on ‘‘Nonmetastatic 

Castration-Resistant Prostate Cancer: 

Considerations for Metastasis-Free 

Survival Endpoint in Clinical Trials.’’ 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 parts 50 and 56 

(Protection of Human Subjects and 

Institutional Review Boards) have been 

approved under OMB control number 

0910–0130. 

III. Electronic Access 

Persons with access to the internet 

may obtain the guidance at either 

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

guidances-drugs, https://www.fda.gov/ 

vaccines-blood-biologics/guidancecompliance-regulatory-informationbiologics, or https://

www.regulations.gov. 

Dated: August 2, 2021. 

Lauren K. Roth, 

Acting Principal Associate Commissioner for 

Policy. 

[FR Doc. 2021–16929 Filed 8–6–21; 8:45 am] 

BILLING CODE 4164–01–P 


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