[Federal Register Volume 83, Number 231 (Friday, November 30, 2018)]
[Notices]
[Pages 61653-61657]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2018-26031]


-----------------------------------------------------------------------

DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2018-N-4131]


Agency Information Collection Activities; Proposed Collection; 
Comment Request; Food and Drug Administration Adverse Event Reports; 
Electronic Submissions

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice.

-----------------------------------------------------------------------

SUMMARY: The Food and Drug Administration (FDA, Agency, or we) is 
announcing an opportunity for public comment on the proposed collection 
of certain information by the Agency. Under the Paperwork Reduction Act 
of 1995 (PRA), Federal Agencies are required to publish notice in the 
Federal Register concerning each proposed collection of information, 
including each proposed extension of an existing collection of 
information, and to allow 60 days for public comment in response to the 
notice. This notice solicits comments on the use of the FDA Electronic 
Submission Gateway (ESG) and the Safety Reporting Portal (SRP) to 
collect adverse event reports and other safety information for FDA-
regulated products.

DATES: Submit either electronic or written comments on the collection 
of information by January 29, 2019.

ADDRESSES: 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 January 29, 2019. The https://www.regulations.gov electronic filing system will accept comments until 
11:59 p.m. Eastern Time at the end of January 29, 2019. 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-2018-N-4131 for ``Agency Information Collection Activities; 
Proposed Collection; Comment Request; FDA Adverse Event Reports; 
Electronic Submissions.'' 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.
     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.gpo.gov/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.

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, 
[email protected].

SUPPLEMENTARY INFORMATION: 

I. Background

    Under the PRA (44 U.S.C. 3501-3520), Federal Agencies must obtain 
approval from the Office of Management and Budget (OMB) for each 
collection of information they conduct or sponsor. ``Collection of 
information'' is defined in 44 U.S.C. 3502(3) and 5 CFR 1320.3(c) and 
includes Agency requests or requirements that members of the public 
submit reports, keep records, or provide information to a third party.

[[Page 61654]]

Section 3506(c)(2)(A) of the PRA (44 U.S.C. 3506(c)(2)(A)) requires 
Federal Agencies to provide a 60-day notice in the Federal Register 
concerning each proposed collection of information, including each 
proposed extension of an existing collection of information, before 
submitting the collection to OMB for approval. To comply with this 
requirement, FDA is publishing notice of the proposed collection of 
information set forth in this document.
    With respect to the following collection of information, FDA 
invites comments on these topics: (1) Whether the proposed collection 
of information is necessary for the proper performance of FDA's 
functions, including whether the information will have practical 
utility; (2) the accuracy of FDA's estimate of the burden of the 
proposed collection of information, including the validity of the 
methodology and assumptions used; (3) ways to enhance the quality, 
utility, and clarity of the information to be collected; and (4) ways 
to minimize the burden of the collection of information on respondents, 
including through the use of automated collection techniques, when 
appropriate, and other forms of information technology.
FDA Adverse Event Reports; Electronic Submissions--21 CFR 310.305, 
314.80, 314.98, 314.540, 514.80, 600.80, 1271.350, and Part 803
OMB Control Number 0910-0645--Extension
    The SRP and the ESG are the Agency's electronic systems for 
collecting, submitting, and processing adverse event reports, product 
problem reports, and other safety information for FDA-regulated 
products. To ensure the safety and identify any risks, harms, or other 
dangers to health for all FDA-regulated human and animal products, the 
Agency needs to be informed whenever an adverse event, product quality 
problem, or product use error occurs. This risk identification process 
is the first necessary step that allows the Agency to gather the 
information necessary to be able to evaluate the risk associated with 
the product and take whatever action is necessary to mitigate or 
eliminate the public's exposure to the risk.
    Some adverse event reports are required to be submitted to FDA 
(mandatory reporting) and some adverse event reports are submitted 
voluntarily (voluntary reporting). Requirements regarding mandatory 
reporting of adverse events or product problems have been codified in 
21 CFR parts 310, 314, 514, 600, 803, and 1271, specifically Sec. Sec.  
[thinsp]310.305, 314.80, 314.98, 314.540, 329.100, 514.80, 600.80, 
803.30, 803.40, 803.50, 803.53, 803.56, and 1271.350(a) (21 CFR 
310.305, 314.80, 314.98, 314.540, 329.100, 514.80, 600.80, 803.30, 
803.40, 803.50, 803.53, 803.56, and 1271.350(a)). While adverse event 
reports submitted to FDA in paper format using Forms FDA 3500, 3500A, 
1932, and 1932a are approved under OMB control numbers 0910-0284 and 
0910-0291, this notice solicits comments on adverse event reports filed 
electronically via the SRP and the ESG, and currently approved under 
OMB control number 0910-0645.

II. The FDA Safety Reporting Portal Rational Questionnaires

    FDA currently has OMB approval to receive several types of adverse 
event reports electronically via the SRP using rational questionnaires. 
In this notice, FDA seeks comments on the extension of OMB approval for 
these existing rational questionnaires and the proposed revision of the 
existing rational questionnaire for tobacco products.

A. Reportable Food Registry Reports

    The Food and Drug Administration Amendments Act of 2007 (Pub. L. 
110-085) (FDAAA) amended the Federal Food, Drug, and Cosmetic Act (FD&C 
Act) by creating section 417 (21 U.S.C. 350f), Reportable Food Registry 
(RFR). Section 417 of the FD&C Act defines ``reportable food'' as an 
article of food (other than infant formula) for which there is a 
``reasonable probability that the use of, or exposure to, such article 
of food will cause serious adverse health consequences or death to 
humans or animals.'' (See section 417(a)(2) of the FD&C Act.) The 
Secretary of Health and Human Services (the Secretary) has delegated to 
the FDA Commissioner the responsibility for administering the FD&C Act, 
including section 417. The purpose of the RFR is to enable the Agency 
to track patterns of adulteration in food to support its efforts to 
target limited inspection resources to protect the public health. We 
designed the RFR report rational questionnaire to enable FDA to quickly 
identify, track, and remove from commerce an article of food (other 
than infant formula and dietary supplements) for which there is a 
reasonable probability that the use of, or exposure to, such article of 
food will cause serious adverse health consequences or death to humans 
or animals. FDA's Center for Food Safety and Applied Nutrition (CFSAN) 
uses the information collected to help ensure that such products are 
quickly and efficiently removed from the market to prevent foodborne 
illnesses. The data elements for RFR reports remain unchanged in this 
request for extension of OMB approval.

B. Reports Concerning Experience With Approved New Animal Drugs

    Section 512(l) of the FD&C Act (21 U.S.C. 360b(l)) and Sec.  
[thinsp]514.80(b) of FDA's regulations require applicants of approved 
new animal drug applications (NADAs) and approved abbreviated new 
animal drug applications (ANADAs) to report adverse drug experiences 
and product/manufacturing defects to the Center for Veterinary Medicine 
(CVM). This continuous monitoring of approved NADAs and ANADAs affords 
the primary means by which FDA obtains information regarding potential 
problems with the safety and efficacy of marketed approved new animal 
drugs as well as potential product/manufacturing problems. Postapproval 
marketing surveillance is important because data previously submitted 
to FDA may no longer be adequate, as animal drug effects can change 
over time and less apparent effects may take years to manifest.
    If an applicant must report adverse drug experiences and product/
manufacturing defects and chooses to do so using the Agency's paper 
forms, the applicant is required to use Form FDA 1932, ``Veterinary 
Adverse Drug Reaction, Lack of Effectiveness, Product Defect Report.'' 
Periodic drug experience reports and special drug experience reports 
must be accompanied by a completed Form FDA 2301, ``Transmittal of 
Periodic Reports and Promotional Material for New Animal Drugs'' (see 
Sec.  [thinsp]514.80(d)). Form FDA 1932a, ``Veterinary Adverse Drug 
Reaction, Lack of Effectiveness or Product Defect Report'' allows for 
voluntary reporting of adverse drug experiences or product/
manufacturing defects by veterinarians and the general public. 
Collection of information using existing paper Forms FDA 2301, 1932, 
and 1932a is approved under OMB control number 0910-0284.
    Alternatively, an applicant may choose to report adverse drug 
experiences and product/manufacturing defects electronically. The 
electronic submission data elements to report adverse drug experiences 
and product/manufacturing defects electronically remain unchanged in 
this request for extension of OMB approval.

C. Animal Food Adverse Event and Product Problem Reports

    Section 1002(b) of FDAAA directed the Secretary to establish an 
early warning and surveillance system to

[[Page 61655]]

identify adulteration of the pet food supply and outbreaks of illness 
associated with pet food. As part of the effort to fulfill that 
directive, the Secretary tasked FDA with developing the instrument that 
would allow consumers to report voluntarily adverse events associated 
with pet food. We developed the Pet Food Early Warning System rational 
questionnaire as a user-friendly data collection tool, to make it easy 
for the public to report a safety problem with pet food. Subsequently, 
we developed a questionnaire for collecting voluntary adverse event 
reports associated with livestock food from interested parties such as 
livestock owners, managers, veterinary staff or other professionals, 
and concerned citizens. Information collected in these voluntary 
adverse event reports contribute to CVM's ability to identify 
adulteration of the livestock food supply and outbreaks of illness 
associated with livestock food. The Pet Food Early Warning System and 
the Livestock Food Reports are designed to identify adulteration of the 
animal food supply and outbreaks of illness associated with animal food 
to enable us to quickly identify, track, and remove from commerce such 
articles of food. We use the information collected to help ensure that 
such products are quickly and efficiently removed from the market to 
prevent foodborne illnesses. The electronic submission data elements to 
report adverse events associated with animal food remain unchanged in 
this request for extension of OMB approval.

D. Voluntary Tobacco Product Adverse Event and Product Problem Reports

    As noted, this notice seeks comments on a revision to the existing 
rational questionnaire utilized by consumers and concerned citizens to 
report tobacco product adverse event or product problems.
    FDA has broad legal authority under the FD&C Act to protect the 
public health, including protecting Americans from tobacco-related 
death and disease by regulating the manufacture, distribution, and 
marketing of tobacco products and by educating the public, especially 
young people, about tobacco products and the dangers their use poses to 
themselves and others. The Family Smoking Prevention and Tobacco 
Control Act (Pub. L. 111-31) amended the FD&C Act by creating a new 
section 909 (21 U.S.C. 387i, Records and Reports on Tobacco Products). 
Section 909(a) of the FD&C Act authorizes FDA to establish regulations 
with respect to mandatory adverse event reports associated with the use 
of a tobacco product. FDA collects voluntary adverse event reports 
associated with the use of tobacco products from interested parties 
such as healthcare providers, researchers, consumers, and other users 
of tobacco products. Information collected in voluntary adverse event 
reports contributes to the Center for Tobacco Product's (CTP's) ability 
to be informed of, and assess the real consequences of, tobacco product 
use.
    The need for this collection of information derives from our 
responsibility to obtain current, timely, and policy-relevant 
information to carry out our statutory functions. FDA's Commissioner is 
authorized to undertake this collection as specified in section 
1003(d)(2) of the FD&C Act (21 U.S.C. 393(d)(2)). FDA's CTP has been 
receiving adverse event and product problem reports through the Safety 
Reporting Portal since January 2014, when the SRP for tobacco products 
first became available to the public. CTP also receives adverse event 
and product problem reports via paper forms, as approved under OMB 
control number 0910-0291. We are revising the questionnaire with non-
substantive changes. The changes are made to make the questions more 
understandable and specific. In some instances, alterations were made 
to the list of values to choose from by the end user to include values 
more pertinent to CTP's current and future data collection needs. In 
one instance, a question was added about the event location: ``In what 
setting(s) did this problem occur?'' In still other instances, 
questions were removed altogether to streamline the questionnaire and 
make it more user-friendly. All changes were made with the goal of 
providing FDA more pertinent information while minimizing the burden on 
the respondent. Finally, we note that respondents unable to submit 
reports using the electronic system will still be able to provide their 
information by paper form (by mail or Fax) or telephone.
    CTP has two voluntary rational questionnaires on the SRP. The first 
is utilized by consumers and concerned citizens to report tobacco 
product adverse event or product problems. A second rational 
questionnaire is used by tobacco product investigators in clinical 
trials with investigational tobacco products. In addition to the 
information collected by the first rational questionnaire for tobacco 
products, the second rational questionnaire collects identifying 
information specific to the clinical trial or investigational product 
such as clinical protocol numbers or other identifying features to 
pinpoint under which test or protocol the adverse event occurred.
    Both CTP voluntary rational questionnaires capture tobacco-specific 
adverse event and product problem information from reporting entities 
such as healthcare providers, researchers, consumers, and other users 
of tobacco products. To carry out its responsibilities, FDA needs to be 
informed when an adverse event, product problem, or error with use is 
suspected or identified. FDA uses tobacco-specific adverse event and 
product problem information to assess and evaluate the risk associated 
with the product and to take whatever action is necessary to reduce, 
mitigate, or eliminate the public's exposure to the risk through 
regulatory and public health interventions. The burden for CTP remains 
unchanged. We seek approval of the revised rational questionnaire in 
this request for extension of OMB approval.

E. Dietary Supplement Adverse Event Reports

    The Dietary Supplement and Nonprescription Drug Consumer Protection 
Act (DSNDCPA) (Pub. L. 109-462, 120 Stat. 3469) amended the FD&C Act 
with respect to serious adverse event reporting and recordkeeping for 
dietary supplements and nonprescription drugs marketed without an 
approved application.
    Section 761(b)(1) of the FD&C Act (21 U.S.C. 379aa-1(b)(1)) 
requires the manufacturer, packer, or distributor whose name (under 
section 403(e)(1) of the FD&C Act (21 U.S.C. 343(e)(1)) appears on the 
label of a dietary supplement marketed in the United States to submit 
to FDA all serious adverse event reports associated with the use of a 
dietary supplement, accompanied by a copy of the product label. The 
manufacturer, packer, or distributor of a dietary supplement is 
required by the DSNDCPA to use the MedWatch form (Form FDA 3500A) when 
submitting a serious adverse event report to FDA. In addition, under 
section 761(c)(2) of the FD&C Act, the submitter of the serious adverse 
event report (referred to in the statute as the ``responsible person'') 
is required to submit to FDA a followup report of any related new 
medical information the responsible person receives within 1 year of 
the initial report.
    As required by section 3(d)(3) of the DSNDCPA, FDA issued guidance 
to describe the minimum data elements for serious adverse event reports 
for dietary supplements. The guidance document entitled ``Guidance for 
Industry: Questions and Answers Regarding

[[Page 61656]]

Adverse Event Reporting and Recordkeeping for Dietary Supplements as 
Required by the Dietary Supplement and Nonprescription Drug Consumer 
Protection Act,'' discusses how, when, and where to submit serious 
adverse event reports for dietary supplements and followup reports. The 
guidance also provides FDA's recommendation on records maintenance and 
access for serious and non-serious adverse event reports and related 
documents.
    Reporting of serious adverse events for dietary supplements to FDA 
serves as an early warning sign of potential public health issues 
associated with such products. Without notification of all serious 
adverse events associated with dietary supplements, FDA would be unable 
to investigate and followup promptly, which in turn could cause delays 
in alerting the public when safety problems are found. In addition, the 
information received provides a reliable mechanism to track patterns of 
adulteration in food that supports efforts by FDA to target limited 
inspection resources to protect the public health. FDA uses the 
information collected to help ensure that such products are quickly and 
efficiently removed from the market to prevent foodborne illnesses.
    Paper mandatory dietary supplement adverse event reports are 
submitted to FDA on the MedWatch form, Form FDA 3500A, and paper 
voluntary reports are submitted on Form FDA 3500. Forms FDA 3500 and 
3500A are available as fillable PDF forms. Dietary supplement adverse 
event reports may be electronically submitted to the Agency via the 
SRP. This method of submission is voluntary. A manufacturer, packer, or 
distributor of a dietary supplement who is unable to or chooses not to 
submit reports using the electronic system will still be able to 
provide their information by paper MedWatch form, Form FDA 3500A (by 
mail or Fax). There is no change to the mandatory information 
previously required on the MedWatch form. CFSAN is making available the 
option to submit the same information via electronic means.
    The reporting and recordkeeping requirements of the FD&C Act for 
dietary supplement adverse event reports and the recommendations of the 
guidance document were first approved in 2009 under OMB control number 
0910-0635. OMB approved the extension of the 0910-0635 collection of 
information in March 2016. OMB approved the electronic submission of 
dietary supplement adverse event reports via the SRP under OMB control 
number 0910-0645 in June 2013. Burden hours are also reported under OMB 
control number 0910-0291, reflecting the submission of dietary 
supplement adverse event reports on the paper MedWatch form, Form FDA 
3500A.
    The electronic submission data elements to report adverse events 
associated with dietary supplement products remain unchanged in this 
request for extension of OMB approval.

F. Food, Infant Formula, and Cosmetic Adverse Event Reports

    We continue to work on proposed new rational questionnaire 
functionality that will be used for food, infant formula, and cosmetic 
adverse event reports over the SRP. Currently, voluntary adverse event 
reports for such products are submitted on Form FDA 3500, which is 
available as a fillable PDF form. However, we have not developed 
rational questionnaires by which these reports may be electronically 
submitted to us via the SRP. In addition, MedWatch forms, although 
recently updated with field labels and descriptions to better clarify 
for reporters the range of reportable products, do not specifically 
include questions relevant for the analysis of adverse events related 
to food, infant formula, and cosmetics. The proposed food, infant 
formula, and cosmetics rational questionnaire functionality will 
operate in a manner similar to the dietary supplement rational 
questionnaire and will include specific questions relevant for the 
analysis of adverse events related to food, infant formula, and 
cosmetics. The electronic submission data elements to report adverse 
events associated with food, infant formula, and cosmetics products 
remain unchanged in this request for extension of OMB approval.

III. Information Collection Burden Estimate

    Description of respondents: The respondents to this collection of 
information include all persons submitting mandatory or voluntary 
adverse event reports electronically to FDA via the ESG or the SRP 
regarding FDA-regulated products.
    We estimate the burden of this collection of information as 
follows:

                                                     Table 1--Estimated Annual Reporting Burden \1\
--------------------------------------------------------------------------------------------------------------------------------------------------------
                                                                  Number of
                   Activity                       Number of     responses per   Total annual          Average burden per response           Total hours
                                                 respondents     respondent       responses
--------------------------------------------------------------------------------------------------------------------------------------------------------
Voluntary Adverse Event Report via the SRP              1,800               1           1,800  0.6 (36 minutes).........................           1,080
 (Other than RFR Reports).
Mandatory Adverse Event Report via the SRP              3,360               1           3,360  1........................................           3,360
 (Other than RFR Reports).
Mandatory Adverse Event Report via the ESG          3,007,000               1       3,007,000  0.6 (36 minutes).........................       1,804,200
 (Gateway-to-Gateway transmission).
Mandatory and Voluntary RFR Reports via the             1,260               1           1,260  0.6 (36 minutes).........................             756
 SRP.
                                              ----------------------------------------------------------------------------------------------------------
    Total....................................  ..............  ..............       3,013,420  .........................................       1,809,396
--------------------------------------------------------------------------------------------------------------------------------------------------------
\1\ There are no capital costs or operating and maintenance costs associated with this collection of information.

    The Agency's estimate of the number of respondents and the total 
annual responses in table 1 is based primarily on mandatory and 
voluntary adverse event reports electronically submitted to the Agency. 
The estimated total annual responses are based on initial reports. 
Followup reports, if any, are not counted as new reports. Based on its 
experience with adverse event reporting, FDA estimates that it will 
take a respondent 0.6 hour to submit a voluntary adverse event report 
via the SRP, 1 hour to submit a mandatory adverse event report via the 
SRP, and 0.6 hour to submit a mandatory adverse event report via the 
ESG (gateway-to-gateway transmission). Both mandatory and voluntary RFR 
reports must be submitted via the SRP. FDA estimates that it will take 
a respondent 0.6 hour to submit a RFR report, whether the submission is 
mandatory or voluntary.

[[Page 61657]]

    The burden hours required to complete paper FDA reporting forms 
(Forms FDA 3500, 3500A, 1932, and 1932a) are reported under OMB control 
numbers 0910-0284 and 0910-0291. While FDA does not charge for the use 
of the ESG, the Agency requires respondents to obtain a public key 
infrastructure certificate to set up the account. This can be obtained 
in-house or outsourced by purchasing a public key certificate that is 
valid for 1 year to 3 years. The certificate typically costs from $20 
to $30.
    Our estimated burden for the information collection reflects an 
overall increase of 688,547 hours and a corresponding increase of 
1,145,763 responses. We attribute this adjustment to an increase in the 
number of submissions we received over the last few years.

    Dated: November 26, 2018.
Leslie Kux,
Associate Commissioner for Policy.
[FR Doc. 2018-26031 Filed 11-29-18; 8:45 am]
 BILLING CODE 4164-01-P