
[Federal Register Volume 81, Number 39 (Monday, February 29, 2016)]
[Notices]
[Pages 10252-10256]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2016-04223]


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

DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2012-N-0921]


Agency Information Collection Activities; Submission for Office 
of Management and Budget Review; Comment Request; Adverse Event 
Reporting; Electronic Submissions

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice.

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

SUMMARY: The Food and Drug Administration (FDA) 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: Fax written comments on the collection of information by March 
30, 2016.

ADDRESSES: To ensure that comments on the information collection are 
received, OMB recommends that written comments be faxed to the Office 
of Information and Regulatory Affairs, OMB, Attn: FDA Desk Officer, 
FAX: 202-395-7285, or emailed to oira_submission@omb.eop.gov. All 
comments should be identified with the OMB control number 0910-0645. 
Also include the FDA docket number found in brackets in the heading of 
this document.

FOR FURTHER INFORMATION CONTACT: FDA PRA Staff, Office of Operations, 
Food and Drug Administration, 8455 Colesville Rd., COLE-14526, Silver 
Spring, MD 20993-0002, PRAStaff@fda.hhs.gov.

SUPPLEMENTARY INFORMATION:

I. Background

    In compliance with 44 U.S.C. 3507, FDA has submitted the following 
proposed collection of information to OMB for review and clearance.

II. Electronic Submission of Food and Drug Administration Adverse Event 
Reports and Other Safety Information Using the Electronic Submission 
Gateway and the Safety Reporting Portal--21 CFR 310.305, 314.80, 
314.98, 314.540, 514.80, 600.80, 1271.350 and Part 803 (OMB Control 
Number 0910--0645)--Revision

    The Safety Reporting Portal (SRP) and the Electronic Submission 
Gateway (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.  
310.305, 314.80, 314.98, 314.540, 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, 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.

III. 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 
the existing rational questionnaires; the proposed revision of the 
existing rational questionnaire for dietary supplements; the proposed 
revision of the existing rational questionnaire for tobacco products; a 
proposed new rational questionnaire that will be used for a new safety 
reporting program for clinical trials and/or investigational use by the 
Center for Tobacco Products (CTP); and proposed new rational 
questionnaires that will be used for food, infant formula, and cosmetic 
adverse event reports.

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 (the 
FD&C Act) by creating section 417 (21 U.S.C. 350f), Reportable Food 
Registry (RFR or the Registry). Section 417 of the FD&C Act defines 
``reportable food'' as an ``article of food (other than infant formula 
or 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.'' 
(See section 417(a)(2) of the FD&C Act). The Secretary of Health and 
Human Services (the Secretary) has delegated to the Commissioner of FDA 
the responsibility for administering the FD&C Act, including section 
417. The Congressionally identified purpose of the RFR is to provide 
``a reliable mechanism to track patterns of adulteration in food 
[which] would support efforts by the Food and Drug Administration to 
target limited inspection resources to protect the public health'' (121 
Stat. 965). 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.  
514.80(b) of FDA's regulations (21 CFR 514.80) require applicants of 
approved new animal drug applications (NADAs) and approved abbreviated 
new animal drug applications (ANADAs) to report

[[Page 10253]]

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.  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 the FDAAA directed the Secretary to establish an 
early warning and surveillance system to 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 two items: (1) A revision 
to the existing rational questionnaire utilized by consumers and 
concerned citizens to report tobacco product adverse event or product 
problems, and (2) a proposed new rational questionnaire that will be 
used for a new safety reporting program for clinical trials and/or 
investigational use by CTP.
    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 of 2009 (Pub. L. 111-31) (Tobacco Control Act) 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 (21 U.S.C. 
387i(a)) authorizes FDA to establish regulations with respect to 
mandatory adverse event reports associated with the use of a tobacco 
product. At this time, FDA collects voluntary adverse event reports 
associated with the use of tobacco products from interested parties 
such as health care providers, researchers, consumers, and other users 
of tobacco products. Information collected in voluntary adverse event 
reports will contribute to 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. The FDA 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 Safety Reporting Portal 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. The original questionnaire evolved with input from a National 
Institutes of Health team of human-factors experts, from other 
regulatory agencies, and with extensive input from consumer advocacy 
groups and the general public. The revised CTP questionnaire along with 
the proposed new Investigator questionnaire build on the foundation of 
the original rational questionnaire to make the report's data more 
useful, analyzable, and specific. The changes from the original to the 
new questionnaire are made in an effort 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 in order to 
include values more pertinent to CTP's current and future data 
collection needs. In other instances, questions were added that will 
provide FDA with more specific, analyzable information. In still other 
instances, questions were removed altogether in an effort 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.
    The proposed new rational questionnaire will be used by tobacco 
product investigators in clinical trials with investigational tobacco 
products. In addition to the information collected by the existing 
rational questionnaire for tobacco products, the proposed rational 
questionnaire will collect identifying information specific to the 
clinical trial or investigational product such as clinical protocol 
numbers or other identifying features to pinpoint under

[[Page 10254]]

which test or protocol the adverse event occurred.
    Both CTP voluntary rational questionnaires will capture tobacco-
specific adverse event and product problem information from voluntary 
reporting entities such as health care 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. When FDA 
receives tobacco-specific adverse event and product problem 
information, it will use the information to assess and evaluate the 
risk associated with the product, and then FDA will take whatever 
action is necessary to reduce, mitigate, or eliminate the public's 
exposure to the risk through regulatory and public health 
interventions.

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 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. However, we 
are proposing to add a new voluntary question on the mandatory report 
rational questionnaire and a new voluntary question on the voluntary 
report rational questionnaire. The text of the new questions is 
provided in table form in table 1. Finally, we are proposing to change 
the following data elements from a text box method of response to an 
individual question and answer method: Race and known allergies.

   Table 1--Proposed New Questions on the Dietary Supplement Rational
                              Questionnaire
------------------------------------------------------------------------
                                             Is response mandatory or
          Text of new question                      voluntary?
------------------------------------------------------------------------
Mandatory Report--In the Contact         Voluntary, and only displayed
 Information section, we propose to       if the person filling out the
 add, ``Please provide contact            report is reporting on behalf
 information for you, the person who is   of a responsible person, such
 filling out this report.''.              as a contractor, and has not
                                          created an account on the SRP.
Voluntary Report--In the Product         Voluntary.
 Information section, we propose to
 request the ingredients of the suspect
 and concomitant product(s), as
 provided on the label of the
 product(s).
------------------------------------------------------------------------

    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 February 2013. 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.

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

    We are planning proposed new rational questionnaire functionality 
that will be used for food, infant formula, and cosmetic adverse event 
reports. 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

[[Page 10255]]

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.

    Table 2--New Questions on the Proposed Food, Infant Formula, and
   Cosmetics Rational Questionnaires for Both Suspect and Concomitant
                                Products
------------------------------------------------------------------------
                                              Is response mandatory or
           Text of new question                      voluntary?
------------------------------------------------------------------------
For food products:........................  Voluntary.
    ``Is this a medical food?''
    ``If so, what was the diagnosis or
     reason for use?''
    ``How was the product prepared?''
For infant formula products:..............  Voluntary.
    ``What form of the product was used:
     Concentrate, powder or ready to
     serve?''
    ``Is this a specialized infant
     formula?''
    ``If so, what was the diagnosis or
     reason for use?''
    ``How was the product prepared?''
    ``What type of water was used to
     prepare the formula?''
For cosmetic products:....................  Voluntary.
    ``Do you have existing skin
     conditions?''
    ``How soon did symptoms develop after
     using the product?''
    ``Did the intensity of the reaction
     get worse with time?''
    ``Where did the reaction develop?''
    ``What treatments were sought for this
     adverse event?''
    ``What ingredient do you suspect
     caused the adverse event?''
    ``Has the problem resolved?''
    ``Does the product label contain a
     warning or caution statement?''
------------------------------------------------------------------------

IV. 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.
    In the Federal Register of November 18, 2015 (80 FR 72071) FDA 
published a 60-day notice requesting public comment on the proposed 
collection of information. No comments were received.
    We estimate the burden of this collection of information as 
follows:

                                 Table 3--Estimated Annual Reporting Burden \1\
----------------------------------------------------------------------------------------------------------------
                                                  Number of
           Activity               Number of     responses per   Total annual    Average  burden     Total hours
                                 respondents     respondent       responses       per response
----------------------------------------------------------------------------------------------------------------
Voluntary Adverse Event                 1,786               1           1,786  0.6..............           1,072
 Report via the SRP (Other                                                     (36 minutes).....
 than RFR Reports).
Mandatory Adverse Event                   636               1             636  1.0..............             636
 Report via the SRP (Other
 than RFR Reports).
Mandatory Adverse Event             1,864,035               1       1,864,035  0.6..............       1,118,421
 Report via the ESG (Gateway-                                                  (36 minutes).....
 to-Gateway transmission).
Mandatory and Voluntary RFR             1,200               1           1,200  0.6..............             720
 Reports via the SRP.                                                          (36 minutes).....
                              ----------------------------------------------------------------------------------
    Total....................  ..............  ..............  ..............  .................       1,120,849
----------------------------------------------------------------------------------------------------------------
\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 3, Estimated Annual Reporting Burden, 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.
    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, FDA requires respondents to obtain a public key 
infrastructure certificate in order to set up the account.

[[Page 10256]]

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.

    Dated: February 23, 2016.
Leslie Kux,
Associate Commissioner for Policy.
[FR Doc. 2016-04223 Filed 2-26-16; 8:45 am]
 BILLING CODE 4164-01-P


