33310 Federal Register / Vol. 86, No. 119 / Thursday, June 24, 2021 / Notices 

‘‘COVID–19: Master Protocols 

Evaluating Drugs and Biological 

Products for Treatment or Prevention.’’ 

This guidance describes FDA’s current 

recommendations regarding master 

protocols for trials evaluating drugs and 

biological products for the treatment or 

prevention of COVID–19. Well-designed 

and -conducted master protocols can 

accelerate drug development by 

maximizing the amount of information 

obtained from the research effort. These 

efficiencies are of particular importance 

in the setting of a public health 

emergency such as the current COVID– 

19 pandemic, where the burden of 

disease is high and there is a critical 

need for the development of therapies. 

This guidance focuses on the trial 

design and conduct as well as statistical 

considerations for master protocols 

intended to generate substantial 

evidence of effectiveness and adequate 

characterization of safety for COVID–19. 

Additionally, this guidance provides 

administrative and procedural 

recommendations to sponsors of master 

protocols for COVID–19. 

In light of the public health 

emergency related to COVID–19 

declared by the Secretary of the 

Department of Health and Human 

Services (HHS), FDA has determined 

that prior public participation for this 

guidance is not feasible or appropriate 

and is issuing this guidance without 

prior public comment (see section 

701(h)(1)(C)(i) of the FD&C Act (21 

U.S.C. 371(h)(1)(C)(i)) and 21 CFR 

10.115(g)(2)). This guidance document 

is being implemented immediately, but 

it remains subject to comment in 

accordance with the Agency’s good 

guidance practice statute and regulation. 

This guidance is intended to remain 

in effect for the duration of the public 

health emergency related to COVID–19 

declared by HHS, including any 

renewals made by the Secretary in 

accordance with section 319(a)(2) of the 

Public Health Service Act (42 U.S.C. 

247d(a)(2)). However, the 

recommendations and processes 

described in the guidance are expected 

to assist the Agency more broadly in its 

continued efforts to assist sponsors in 

the clinical development of drugs for 

the treatment or prevention of COVID– 

19 beyond the termination of the 

COVID–19 public health emergency and 

reflect the Agency’s current thinking on 

this issue. Therefore, within 60 days 

following the termination of the public 

health emergency, FDA intends to revise 

and replace this guidance with any 

appropriate changes based on comments 

received on this guidance and the 

Agency’s experience with 

implementation. 

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 ‘‘COVID–19: Master 

Protocols Evaluating Drugs and 

Biological Products for Treatment or 

Prevention.’’ 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, 

Investigational New Drug Application, 

have been approved under OMB control 

number 0910–0014 and the collections 

of information required for institutional 

review boards and informed consent are 

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, https://www.fda.gov/ 

regulatory-information/search-fdaguidance-documents, https://

www.fda.gov/emergency-preparednessand-response/coronavirus-disease-2019- 

covid-19/covid-19-related-guidancedocuments-industry-fda-staff-and-otherstakeholders, or https:// 

www.regulations.gov. 

Dated: June 16, 2021. 

Lauren K. Roth, 

Acting Principal Associate Commissioner for 

Policy. 

[FR Doc. 2021–13394 Filed 6–23–21; 8:45 am] 

BILLING CODE 4164–01–P 

DEPARTMENT OF HEALTH AND 

HUMAN SERVICES 

Food and Drug Administration 

[Docket No. FDA–1995–D–0288 (Formerly 

Docket No. 95D–0052)] 

Chemistry, Manufacturing, and 

Controls Changes to an Approved 

Application: Certain Biological 

Products; 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 document entitled 

‘‘Chemistry, Manufacturing, and 

Controls Changes to an Approved 

Application: Certain Biological 

Products.’’ The guidance is intended to 

assist applicants and manufacturers of 

certain licensed biological products in 

determining which reporting category is 

appropriate for a change in chemistry, 

manufacturing, and controls (CMC) 

information to an approved biologics 

license application (BLA). The guidance 

describes general and administrative 

information on evaluating and reporting 

changes and recommendations for 

reporting categories based on a tieredreporting system for specific changes. 

The guidance announced in this notice 

finalizes the draft guidance, ‘‘Chemistry, 

Manufacturing, and Controls Changes to 

an Approved Application: Certain 

Biological Products,’’ dated December 

2017 and supersedes the document 

entitled ‘‘Guidance for Industry: 

Changes to an Approved Application: 

Biological Products,’’ dated July 1997 

(July 1997 guidance). 

DATES: The announcement of the 

guidance is published in the Federal 

Register on June 24, 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 


khammond on DSKJM1Z7X2PROD with NOTICES
Federal Register / Vol. 86, No. 119 / Thursday, June 24, 2021 / Notices 33311 

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– 

1995–D–0288 (Formerly Docket No. 

95D–0052) for ‘‘Chemistry, 

Manufacturing, and Controls Changes to 

an Approved Application: Certain 

Biological Products.’’ 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; or 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 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: 

Victoria Wagman, 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 final guidance document entitled 

‘‘Chemistry, Manufacturing, and 

Controls Changes to an Approved 

Application: Certain Biological 

Products.’’ The guidance document is 

intended to assist applicants and 

manufacturers of licensed biological 

products in determining which 

reporting category is appropriate for a 

change in CMC to an approved BLA as 

specified in § 601.12 (21 CFR 601.12). 

The guidance document provides 

applicants and manufacturers general 

and administrative information on 

evaluating and reporting changes and 

recommendations for reporting 

categories based on a tiered-reporting 

system for specific changes under 

§ 601.12. 

FDA issued the July 1997 guidance 

(62 FR 39904; July 24, 1997) to assist 

applicants in determining which 

reporting mechanism is appropriate for 

reporting a change to an approved 

application to reduce the burden on 

manufacturers when reporting changes 

and to facilitate the approval process of 

the change being made. FDA is updating 

the July 1997 guidance to accommodate 

advances in manufacturing and testing 

technology and to clarify FDA’s current 

thinking on assessing reportable 

changes. The updated guidance applies 

to certain biological products licensed 

under section 351(a) of the Public 

Health Service Act (PHS Act) (42 U.S.C. 

262(a)). The guidance applies to all 

manufacturing locations, including 

contract locations. The following 

biological products are not within the 

scope of this guidance: (1) Whole blood, 

blood components (including source 

plasma), and source leukocytes; (2) 

specified biotechnology products 

described in § 601.2(a); and (3) 

biosimilar and interchangeable products 

subject to licensure under section 351(k) 

of the PHS Act. The guidance also does 

not apply to human cells, tissues, and 

cellular and tissue-based products 

regulated solely under section 361 of the 

PHS Act (42 U.S.C. 264) and the 

regulations in 21 CFR part 1271. 

In the Federal Register of December 

22, 2017 (82 FR 60750), FDA announced 

the availability of the draft guidance of 

the same title dated December 2017. 

FDA received several comments on the 

draft guidance and those comments 

were considered as the guidance was 

finalized. The guidance was updated to 

reflect the ICH Harmonised Guideline: 

Technical and Regulatory 

Considerations for Pharmaceutical 

Product Lifecycle Management: Q12, 

which was issued after publication of 

the draft guidance on November 11, 

2019. In addition, editorial changes 

were made to improve clarity. The 

guidance announced in this notice 

finalizes the draft guidance dated 

December 2017. The guidance also 

supersedes the July 1997 guidance. 

This guidance is being issued 

consistent with FDA’s good guidance 

practices regulation (21 CFR 10.115). 

The guidance represents the current 


khammond on DSKJM1Z7X2PROD with NOTICES
33312 Federal Register / Vol. 86, No. 119 / Thursday, June 24, 2021 / Notices 

thinking of FDA on ‘‘Chemistry, 

Manufacturing, and Controls Changes to 

an Approved Application: Certain 

Biological Products.’’ 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 210 and 21 

CFR part 211 have been approved under 

OMB control number 0910–0139; the 

collections of information in 21 CFR 

601.12 have been approved under OMB 

control numbers 0910–0338, and the 

collections of information in 21 CFR 

part 820 have been approved under 

OMB control number 0910–0073. 

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, https://

www.fda.gov/regulatory-information/ 

search-fda-guidance-documents, or 

https://www.regulations.gov. 

Dated: June 15, 2021. 

Lauren K. Roth, 

Acting Principal Associate Commissioner for 

Policy. 

[FR Doc. 2021–13392 Filed 6–23–21; 8:45 am] 

BILLING CODE 4164–01–P 

DEPARTMENT OF HEALTH AND 

HUMAN SERVICES 

Food and Drug Administration 

[Docket No. FDA–2021–N–0512] 

Considerations for Progressive 

Multifocal Leukoencephalopathy 

Clinical Trial Designs; Public 

Workshop; Request for Comments 

AGENCY: Food and Drug Administration, 

HHS. 

ACTION: Notice of public workshop; 

request for comments. 

SUMMARY: The Food and Drug 

Administration (FDA or Agency) is 

announcing the following public 

workshop entitled ‘‘Considerations for 

Progressive Multifocal 

Leukoencephalopathy Clinical Trial 

Designs.’’ The purpose of the public 

workshop is to discuss the challenges 

and clinical trial design considerations 

for developing therapeutic products for 

the treatment of progressive multifocal 

leukoencephalopathy (PML). 

DATES: The public workshop will be 

held virtually on September 21, 2021, 

from 10 a.m. to 4:15 p.m., Eastern Time. 

Submit either electronic or written 

comments on this public workshop by 

November 1, 2021. See the 

SUPPLEMENTARY INFORMATION section for 

registration date and information. 

ADDRESSES: The public workshop will 

be held in virtual format only. 

You may submit comments as 

follows. Please note that late, untimely 

filed comments will not be considered. 

Electronic comments must be submitted 

on or before November 1, 2021. The 

https://www.regulations.gov electronic 

filing system will accept comments 

until 11:59 p.m. Eastern Time at the end 

of November 1, 2021. Comments 

received by mail/hand delivery/courier 

(for written/paper submissions) will be 

considered timely if they are 

postmarked or the delivery service 

acceptance receipt is on or before that 

date. 

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– 

2021–N–0512 for ‘‘Considerations for 

Progressive Multifocal 

Leukoencephalopathy Clinical Trial 

Designs.’’ Received comments, those 

filed in a timely manner (see 

ADDRESSES), 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 


khammond on DSKJM1Z7X2PROD with NOTICES