Federal Register / Vol. 86, No. 34 / Tuesday, February 23, 2021 / Notices 10975 

DEPARTMENT OF HEALTH AND 

HUMAN SERVICES 

Food and Drug Administration 

[Docket No. FDA–2011–N–0231] 

Agency Information Collection 

Activities; Submission for Office of 

Management and Budget Review; 

Comment Request; Adverse 

Experience Reporting for Licensed 

Biological Products; and General 

Records 

AGENCY: Food and Drug Administration, 

HHS. 

ACTION: Notice. 

SUMMARY: The Food and Drug 

Administration (FDA or we) 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: Submit written comments 

(including recommendations) on the 

collection of information by March 25, 

2021. 

ADDRESSES: To ensure that comments on 

the information collection are received, 

OMB recommends that written 

comments be submitted to https://

www.reginfo.gov/public/do/PRAMain. 

Find this particular information 

collection by selecting ‘‘Currently under 

Review—Open for Public Comments’’ or 

by using the search function. The OMB 

control number for this information 

collection is 0910–0308. Also include 

the FDA docket number found in 

brackets in the heading of this 

document. 

FOR FURTHER INFORMATION CONTACT: 

Domini Bean, Office of Operations, 

Food and Drug Administration, Three 

White Flint North, 10A–12M, 11601 

Landsdown St., North Bethesda, MD 

20852, 301–796–5733, 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. 

Adverse Experience Reporting for 

Licensed Biological Products and 

General Records—21 CFR Part 600 

OMB Control Number 0910–0308— 

Extension 

Under the Public Health Service Act 

(42 U.S.C. 262), FDA may only approve 

a biologics license application for a 

biological product that is safe, pure, and 

potent. When a biological product is 

approved and enters the market, the 

product is introduced to a larger patient 

population in settings different from 

clinical trials. New information 

generated during the postmarketing 

period offers further insight into the 

benefits and risks of the product, and 

evaluation of this information is 

important to ensure its safe use. FDA 

issued its Adverse Experience Reporting 

System (FAERS) requirements in part 

600 (21 CFR part 600) to enable FDA to 

take actions necessary for the protection 

of the public health in response to 

reports of adverse experiences related to 

licensed biological products. The 

primary purpose of FAERS is to identify 

potentially serious safety problems with 

licensed biological products. Although 

premarket testing discloses a general 

safety profile of a biological product’s 

comparatively common adverse effects, 

the larger and more diverse patient 

populations exposed to the licensed 

biological product provides the 

opportunity to collect information on 

rare, latent, and long-term effects. In 

addition, production and/or distribution 

problems have contaminated biological 

products in the past. 

FAERS reports are obtained from a 

variety of sources, including 

manufacturers, patients, physicians, 

foreign regulatory agencies, and clinical 

investigators. Identification of new and 

unexpected safety issues through the 

analysis of the data in FAERS 

contributes directly to increased public 

health protection. For example, 

evaluation of these safety issues enables 

FDA to take focused regulatory action. 

Such action may include, but is not 

limited to, important changes to the 

product’s labeling (such as adding a 

new warning), coordination with 

manufacturers to ensure adequate 

corrective action is taken, and removal 

of a biological product from the market 

when necessary. 

Section 600.80(c)(1) requires licensed 

manufacturers or any person whose 

name appears on the label of a licensed 

biological product to report each 

adverse experience that is both serious 

and unexpected, whether foreign or 

domestic, as soon as possible but in no 

case later than 15 calendar days of 

initial receipt of the information by the 

licensed manufacturer. These reports 

are known as postmarketing 15-day 

Alert reports. This section also requires 

licensed manufacturers to submit any 

followup reports within 15 calendar 

days of receipt of new information or as 

requested by FDA, and if additional 

information is not obtainable, to 

maintain records of the unsuccessful 

steps taken to seek additional 

information. In addition, this section 

requires that a person who submits an 

adverse action report to the licensed 

manufacturer, rather than to FDA, 

maintain a record of this action. 

Section 600.80(e) requires licensed 

manufacturers to submit a 15-day Alert 

report for an adverse experience 

obtained from a postmarketing clinical 

study only if the licensed manufacturer 

concludes that there is a reasonable 

possibility that the product caused the 

adverse experience. 

Section 600.80(c)(2) requires licensed 

manufacturers to report each adverse 

experience not reported in a 

postmarketing 15-day Alert report at 

quarterly intervals, for 3 years from the 

date of issuance of the biologics license, 

and then at annual intervals. The 

majority of these periodic reports are 

submitted annually, since a large 

percentage of currently licensed 

biological products have been licensed 

longer than 3 years. 

Section 600.80(k) requires licensed 

manufacturers to maintain for a period 

of 10 years records of all adverse 

experiences known to the licensed 

manufacturer, including raw data and 

any correspondence relating to the 

adverse experiences. 

Section 600.81 requires licensed 

manufacturers to submit, at an interval 

of every 6 months, information about 

the quantity of the product distributed 

under the biologics license, including 

the quantity distributed to distributors. 

These distribution reports provide FDA 

with important information about 

products distributed under biologics 

licenses, including the quantity, certain 

lot numbers, labeled date of expiration, 

the fill lot numbers for the total number 

of dosage units of each strength or 

potency distributed (e.g., 50,000 per 10- 

milliliter vials), and date of release. FDA 

may require the licensed manufacturer 

to submit distribution reports under this 

section at times other than every 6 

months. 

Under § 600.82(a), an applicant of a 

biological product or blood and blood 

component must notify FDA of a 

permanent discontinuance of 

manufacture or an interruption in 

manufacturing or disruption in supply, 

as applicable. Under §§ 600.80(h)(2) and 

600.81(b)(2), a licensed manufacturer 

may request a temporary waiver for the 

requirements under §§ 600.80(h)(1) and 

600.80(b)(1), respectively. Requests for 

waivers must be submitted in 

accordance with § 600.90. Under 

§ 600.90, a licensed manufacturer may 

submit a waiver request for any 

requirements that apply to the licensed 

manufacturer under §§ 600.80 and 

600.81. A waiver request submitted 

under § 600.90 must include supporting 

documentation. 

10976 Federal Register / Vol. 86, No. 34 / Tuesday, February 23, 2021 / Notices 

Manufacturers of biological products 

for human use must keep records of 

each step in the manufacture and 

distribution of a product, including any 

recalls. These recordkeeping 

requirements serve preventative and 

remedial purposes by establishing 

accountability and traceability in the 

manufacture and distribution of 

products. These requirements also 

enable FDA to perform meaningful 

inspections. 

Section 600.12 requires, among other 

things, that records be made 

concurrently with the performance of 

each step in the manufacture and 

distribution of products. These records 

must be retained for no less than 5 years 

after the records of manufacture have 

been completed or 6 months after the 

latest expiration date for the individual 

product, whichever represents a later 

date. In addition, under § 600.12, 

manufacturers must maintain records 

relating to the sterilization of equipment 

and supplies, animal necropsy records, 

and records in cases of divided 

manufacturing responsibility with 

respect to a product. 

Under § 600.12(b)(2), manufacturers 

are also required to maintain complete 

records pertaining to the recall from 

distribution of any product. 

Furthermore, 21 CFR 610.18(b) requires, 

in part, that the results of all periodic 

tests for verification of cultures and 

determination of freedom from 

extraneous organisms be recorded and 

retained. The recordkeeping 

requirements for 21 CFR 610.12(g), 

610.13(a)(2), 610.18(d), 680.2(f) and 

680.3(f) are approved under OMB 

control number 0910–0139. 

Respondents to this collection of 

information include manufacturers of 

biological products (including blood 

and blood components) and any person 

whose name appears on the label of a 

licensed biological product. In table 1, 

the number of respondents is based on 

the estimated number of manufacturers 

that are subject to those regulations or 

that submitted the required information 

to the Center for Biologics Evaluation 

and Research and the Center for Drugs 

Evaluation and Research, FDA, in fiscal 

year (FY) 2019. Based on information 

obtained from the FDA’s database 

system, there were 103 manufacturers of 

biological products. This number 

excludes those manufacturers who 

produce Whole Blood, components of 

Whole Blood, or in-vitro diagnostic 

licensed products, because of the 

exemption under § 600.80(m). 

The total annual responses are based 

on the number of submissions received 

by FDA in FY 2019. There were an 

estimated 169,334 15-day Alert reports, 

184,265 periodic reports, and 789 lot 

distribution reports submitted to FDA. 

The number of 15-day Alert reports for 

postmarketing studies under § 600.80(e) 

is included in the total number of 15- 

day Alert reports. FDA received 63 

requests from 40 manufacturers for 

waivers under § 600.90 (including 

§§ 600.80(h)(2) and 600.81(b)(2)), of 

which 61 were granted. The hours per 

response are based on FDA experience. 

The burden hours required to complete 

the MedWatch Form (Form FDA 3500A) 

for § 600.80(c)(1), (e), and (f) are 

reported under OMB control number 

0910–0291. 

In the Federal Register of September 

1, 2020 (85 FR 54385), we published a 

60-day notice requesting public 

comment on the proposed collection of 

information. One comment was received 

but was not responsive to the 

information collection topics solicited. 

We estimate the burden of the 

collection of information as follows: 

TABLE 1—ESTIMATED ANNUAL REPORTING BURDEN 1

21 CFR section Number of 

respondents 

Number of 

responses per 

respondent 

Total annual 

responses 

Average 

burden per 

response 

(in hours) 

Total hours 

600.80(c)(1), 600.80(d), 600.80(e); postmarketing 15-day 

Alert reports ...................................................................... 103 1,644.02 169,334 1 169,334 

600.82; notification of discontinuance or interruption in 

manufacturing ................................................................... 21 1.67 35 2 70 

600.80(c)(2) periodic adverse experience reports (FAERS) 103 1,788.98 184,265 28 5,159,420 

600.81; distribution reports .................................................. 117 6.744 789 1 789 

600.80(h)(2), 600.81(b)(2), 600.90; waiver requests ........... 40 1.575 63 1 63 

Total .............................................................................. ........................ ........................ ........................ ........................ 5,329,676 

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

In table 2, the number of respondents 

is based on the number of 

manufacturers subject to those 

regulations. Based on information 

obtained from FDA’s database system, 

there were 212 licensed manufacturers 

of biological products in FY 2019. 

However, the number of recordkeepers 

listed for § 600.12(a) through (e), 

excluding (b)(2), is estimated to be 109. 

This number excludes manufacturers of 

blood and blood components because 

their burden hours for recordkeeping 

have been reported under § 606.160 in 

OMB control number 0910–0116. The 

total annual records is based on the 

annual average of lots released in FY 

2019 (6,670), number of recalls made 

(735), and total number of adverse 

experience reports received (305,951) in 

FY 2019. The hours per record are based 

on FDA experience. 

TABLE 2—ESTIMATED ANNUAL RECORDKEEPING BURDEN 1

21 CFR section; activity Number of 

recordkeepers 

Number of 

records per 

recordkeeper 

Total annual 

records 

Average 

burden per 

recordkeeper 

(in hours) 

Total hours 

600.12; 2 maintenance of records ........................................ 109 61.19 6,670 32 213,440 

600.12(b)(2); recall records ................................................. 212 3.467 735 24 17,640 

600.80(c)(1) and 600.80(k); FAERS records ....................... 103 3,433 353,599 1 353,599 

Federal Register / Vol. 86, No. 34 / Tuesday, February 23, 2021 / Notices 10977 

TABLE 2—ESTIMATED ANNUAL RECORDKEEPING BURDEN 1—Continued 

21 CFR section; activity Number of 

recordkeepers 

Number of 

records per 

recordkeeper 

Total annual 

records 

Average 

burden per 

recordkeeper 

(in hours) 

Total hours 

Total .............................................................................. ........................ ........................ ........................ ........................ 584,679 

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

2The recordkeeping requirements in § 610.18(b) are included in the estimate for § 600.12. 

The burden for this information 

collection has changed since the last 

OMB approval. The reporting and 

recordkeeping burden has increased 

mostly due to an increase in the number 

of FAERS reports submitted to FDA and 

the associated recordkeeping with these 

reports. 

Dated: February 16, 2021. 

Lauren K. Roth, 

Acting Principal Associate Commissioner for 

Policy. 

[FR Doc. 2021–03541 Filed 2–22–21; 8:45 am] 

BILLING CODE 4164–01–P 

DEPARTMENT OF HEALTH AND 

HUMAN SERVICES 

Food and Drug Administration 

[Docket No. FDA–2020–D–2016] 

Policy for Testing of Alcohol (Ethanol) 

and Isopropyl Alcohol for Methanol, 

Including During the Public Health 

Emergency (COVID–19); 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 ‘‘Policy 

for Testing of Alcohol (Ethanol) and 

Isopropyl Alcohol for Methanol, 

Including During the Public Health 

Emergency (COVID–19).’’ This guidance 

is intended to alert pharmaceutical 

manufacturers and pharmacists in Statelicensed pharmacies or Federal facilities 

who engage in drug compounding to the 

potential public health hazard of 

alcohol (ethyl alcohol or ethanol) or 

isopropyl alcohol contaminated with or 

substituted with methanol. FDA is 

aware of reports of fatal methanol 

poisoning of consumers who ingested 

alcohol-based hand sanitizers that were 

manufactured with methanol or 

methanol-contaminated ethanol and is 

concerned that other drug products 

containing ethanol or isopropyl alcohol 

(pharmaceutical alcohol), which are 

widely used active ingredients in a 

variety of drug products, could be 

similarly vulnerable to methanol 

contamination. As the COVID–19 

pandemic has increased the demand for 

hand sanitizer products, the demand for 

pharmaceutical alcohol as the active 

ingredient of those products has also 

increased. The guidance outlines a 

policy intended to help pharmaceutical 

manufacturers and pharmacists in Statelicensed pharmacies or Federal facilities 

who engage in drug compounding avoid 

the use of pharmaceutical alcohol that is 

contaminated with or substituted with 

methanol in drug products. Given the 

public health emergency presented by 

coronavirus disease 2019 (COVID–19), 

this guidance document is being 

implemented without prior public 

comment because FDA has determined 

that prior public participation is not 

feasible or appropriate, but it remains 

subject to comment in accordance with 

the Agency’s good guidance practices. 

DATES: The announcement of the 

guidance is published in the Federal 

Register on February 23, 2021. The 

guidance document is immediately in 

effect, but it remains subject to comment 

in accordance with the Agency’s good 

guidance practices. 

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–2016 for ‘‘Policy for Testing of 

Alcohol (Ethanol) and Isopropyl 

Alcohol for Methanol, Including During 

the Public Health Emergency (COVID– 

19).’’ 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