[Federal Register Volume 83, Number 177 (Wednesday, September 12, 2018)]
[Notices]
[Pages 46166-46170]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2018-19742]


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

DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2014-N-1960]


Agency Information Collection Activities; Submission for Office 
of Management and Budget Review; Comment Request; MedWatch: The Food 
and Drug Administration Medical Products Reporting Program

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 October 
12, 2018.

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 [email protected]. All 
comments should be identified with the OMB control number 0910-0291 and 
title ``MedWatch: The Food and Drug Administration Medical Products 
Reporting Program.'' 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, 
[email protected].

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.

MedWatch: The FDA Medical Products Reporting Program

OMB Control Number 0910-0291--Revision

    This information collection supports FDA's MedWatch safety 
information and adverse event reporting program. Members of the public 
use FDA's MedWatch system to report adverse events, product problems, 
errors with the use of a human medical product, or when evidence of 
therapeutic failure is suspected or identified in clinical use.

[[Page 46167]]

To ensure the marketing of safe and effective products, it is critical 
that postmarketing adverse outcomes and product problems are reported 
for all FDA-regulated human healthcare products, including drugs 
(prescription and nonprescription), biologics, medical devices, dietary 
supplements, and other special nutritional products (e.g. infant 
formula and medical foods), and cosmetics. To facilitate reporting on 
human medical products (except vaccines) during their postapproval and 
marketed lifetimes, we have developed three forms (collectively known 
as the MedWatch forms). Form FDA 3500 is intended to be used for 
voluntary (i.e., not mandated by law or regulation) reporting by 
healthcare professionals; Form FDA 3500A is used for mandatory 
reporting (i.e., required by law or regulation); and Form FDA 3500B is 
written in plain language and is intended to be used for voluntary 
reporting (i.e., not mandated by law or regulation) by consumers (i.e., 
patients and their caregivers). Information collected by the forms is 
used to assess and evaluate risks associated with FDA-regulated 
products, enabling us to take appropriate action to reduce, mitigate, 
or eliminate the public's exposure to the risk through regulatory and 
public health interventions.

I. Background

A. Authorizing Statutes and Codified Regulations

    The Federal Food, Drug, and Cosmetic Act (FD&C Act) (21 U.S.C. 
353b, 355, 360i, 360l, and 393) and the Public Health Service Act (42 
U.S.C. 262) require FDA to collect mandatory adverse event reports from 
regulated industry on medical products once they have been approved for 
marketing, enabling the Agency to monitor the safety of drugs, 
biologics, medical devices, and dietary supplements. Postmarket 
reporting for medical foods, infant formula, cosmetics, and tobacco 
products is done voluntarily.
    Requirements regarding mandatory reporting of adverse events or 
product problems are codified at parts 310, 314, 600, and 803 (21 CFR 
parts 310, 314, 600, and 803), specifically Sec. Sec.  310.305, 314.80, 
314.98, 600.80, 803.30, 803.50, 803.53, 803.56, and specified in 
sections 503B, 760, and 761 of the FD&C Act (21 U.S.C. 353b, 379aa, and 
379aa-1). Mandatory reporting of adverse reactions for human cells, 
tissues, and cellular- and tissue-based products (HCT/Ps) is codified 
at Sec.  1271.350 (21 CFR 1271.350).

B. Voluntary Reporting: Form FDA 3500

    Voluntary reporting of adverse events is completed using Form FDA 
3500 and may be used by healthcare professionals to submit all reports 
not mandated by Federal law or regulation. Individual health 
professionals are not required by law or regulation to submit reports 
to the Agency or the manufacturer with the exception of Childhood 
Vaccine Injury Act of 1986 (42 U.S.C. 300aa-1). Reports for vaccines 
are not submitted via MedWatch or MedWatch forms, but are submitted to 
the Vaccines Adverse Event Reporting System, which is jointly 
administered by FDA and the Centers for Disease Control and Prevention 
and approved under OMB control number 0910-0308.
    Hospitals are not required by Federal law or regulation to submit 
reports associated with drug products, biological products, or special 
nutritional products. However, hospitals and other user facilities are 
required by Federal law to report medical device-related deaths and 
serious injuries. Under Federal law and regulation, section 761(b)(1) 
of the FD&C Act, a dietary supplement manufacturer, packer, or 
distributor whose name appears on the label of a dietary supplement 
marketed in the United States is required to submit to FDA any serious 
adverse event report it receives regarding use of the dietary 
supplement in the United States. However, FDA bears the burden to 
gather and review evidence that a dietary supplement may be adulterated 
under section 402 of the FD&C Act (21 U.S.C. 342) after that product is 
marketed. Therefore, the Agency depends on the voluntary reporting by 
health professionals, and especially by consumers, of suspected serious 
adverse events and product quality problems associated with the use of 
dietary supplements. All dietary supplement reports were previously 
received by the Agency on paper versions of Form FDA 3500 (or Form FDA 
3500B) (by mail or Fax). Currently, electronic reports may be sent to 
the Agency via an online submission route called the Safety Reporting 
Portal (https://www.safetyreporting.hhs.gov/ approved under OMB control 
number 0910-0645). In that case, Form FDA 3500 (or Form FDA 3500B) is 
not used.
    Form FDA 3500 may be used to report to the Agency serious adverse 
events, product problems, and product use errors and therapeutic 
failures. The form is provided in both paper and electronic formats. 
Reporters may mail or Fax paper forms to the Agency (a fillable PDF 
version of the form is available at https://www.fda.gov/downloads/AboutFDA/ReportsManualsForms/Forms/UCM163919.pdf) or reporters may 
electronically submit a report via the MedWatch Online Voluntary 
Reporting Form (https://www.accessdata.fda.gov/scripts/medwatch/). 
Reporting is supported for drugs, non-vaccine biologicals, medical 
devices, special nutritional products, cosmetics, and non-prescription 
(over-the-counter (OTC)) human drug products marketed without an 
approved application. The paper form may also be used to submit reports 
about tobacco products and dietary supplements. Electronic reports for 
tobacco products and dietary supplements may be submitted to the Agency 
via an online submission route called the Safety Reporting Portal 
(https://www.safetyreporting.hhs.gov/).

C. Mandatory Reporting: Form FDA 3500A

1. Drug and Biological Products
    In sections 505(b) and (j), 503B, and 704 (21 U.S.C. 355(b) and 
(j), 353B, and 374) of the FD&C Act, Congress has required that 
important safety information relating to all human drug products be 
made available to FDA so that it can take appropriate action to protect 
the public health when necessary. Section 702 of the FD&C Act (21 
U.S.C. 372) authorizes investigational powers to FDA for enforcement of 
the FD&C Act. These statutory requirements regarding mandatory 
reporting have been codified by FDA under parts 310 and 314 (drugs) and 
600 (biological products). Mandatory reporting of adverse reactions for 
HCT/Ps has been codified in Sec.  1271.350.
2. OTC Monograph Drug Products and Dietary Supplements
    Section 760 of the FD&C Act provides for mandatory safety reporting 
for non-prescription human drug products marketed without an approved 
application as described in the Dietary Supplement and Nonprescription 
Drug Consumer Protection Act (Pub. L. 109-462), which became law on 
December 22, 2006. The law requires manufacturers, packers, and 
distributors of nonprescription, OTC human drug products marketed 
without an approved application (OTC monograph drug products) to submit 
reports of adverse experiences from domestic sources. The law also 
requires reports of serious adverse events to be submitted to FDA by 
manufacturers of dietary supplements.

[[Page 46168]]

3. Postmarketing Safety Reports--Changes in Format Starting in June 
2018
    Current requirements specify that postmarketing adverse experience 
reports must be submitted on paper on Form FDA 3500A (or the CIOMS) 
(Council for International Organizations of Medical Sciences) I form 
for serious, unexpected adverse experiences from a foreign source). For 
the last several years the Agency has accepted electronic submissions 
in lieu of the paper Form FDA 3500A on the condition they are submitted 
in a manner that the Agency can process, review, and archive. On June 
10, 2014, the Agency issued a final rule entitled ``Postmarketing 
Safety Reports for Human Drug and Biological Products; Electronic 
Submission Requirements'' (79 FR 33072) that requires electronic 
submission of all mandatory postmarketing safety reports, including 
individual case safety reports. Entities with mandatory reporting 
obligations under parts 310 and 314 (drugs) and 600 (biological 
products) and specified under section 760 of the FD&C Act must 
implement this rule within 1 year of the issuance date (by June 10, 
2015). For more information see: https://www.gpo.gov/fdsys/pkg/FR-2014-06-10/pdf/2014-13480.pdf.
4. Medical Device Products
    Section 519 of the FD&C Act (21 U.S.C. 360i) requires manufacturers 
and importers of devices intended for human use to establish and 
maintain records, make reports, and provide information, as the 
Secretary of Health and Human Services may, by regulation, reasonably 
be required to provide assurance that such devices are not adulterated 
or misbranded and to otherwise assure its safety and effectiveness. The 
Safe Medical Devices Act of 1990 (Pub. L. 101-629), signed into law on 
November 28, 1990, amends section 519 of the FD&C Act. The amendment 
requires that user facilities such as hospitals, nursing homes, 
ambulatory surgical facilities, and outpatient treatment facilities 
report deaths related to medical devices to FDA and to the 
manufacturer, if known. Serious illnesses and injuries are to be 
reported to the manufacturer or to FDA if the manufacturer is not 
known. These statutory requirements regarding mandatory reporting have 
been codified by FDA under part 803. Part 803 mandates the use of Form 
FDA 3500A for reporting to FDA on medical devices. The Medical Device 
User Fee and Modernization Act of 2002 (MDUFMA) (Pub. L. 107-250), 
signed into law October 26, 2002, amended section 519 of the FD&C Act. 
The MDUFMA amendment (section 303) required FDA to revise the MedWatch 
forms to facilitate the reporting of information relating to 
reprocessed single-use devices, including the name of the reprocessor 
and whether the device has been reused.

D. Voluntary Reporting by Consumers: Form FDA 3500B

    Form FDA 3500B was developed for voluntary reporting by consumers 
(i.e. patients and their caregivers) to submit reports not mandated by 
Federal law or regulation. Individual patients or their caregivers are 
not required by law or regulation to submit reports to the Agency or 
the manufacturer.
    FDA supports and encourages direct reporting to the Agency by 
consumers and healthcare professionals of suspected serious adverse 
outcomes and other product problems associated with human medical 
products, (https://www.fda.gov/Safety/ReportaProblem/default.htm). FDA 
has further encouraged voluntary reporting by requiring inclusion of 
the MedWatch toll-free phone number or the MedWatch internet address on 
all outpatient drug prescriptions dispensed, as mandated by section 17 
of the Best Pharmaceuticals for Children Act (Pub. L. 107-109).
    On March 25, 2008, section 906 of the Food and Drug Administration 
Amendments Act of 2007 (Pub. L. 110-85) amended section 502(n) of the 
FD&C Act (21 U.S.C. 352(n)) and mandated that published direct-to-
consumer advertisements for prescription drugs include the following 
statement printed in conspicuous text (this includes vaccine products): 
``You are encouraged to report negative side effects of prescription 
drugs to the FDA. Visit https://www.fda.gov/safety/medwatch, or call 1-
800-FDA-1088.''
    Most private vendors of consumer medication information, the drug 
product-specific instructions dispensed to consumers at outpatient 
pharmacies, remind patients to report ``side effects'' to FDA and 
provide contact information to permit reporting via the MedWatch 
process. For this reporting FDA has created Form FDA 3500B, a modified 
version of Form FDA 3500 tailored for consumers and written in plain 
language (in conformance with the Plain Writing Act of 2010 (Pub. L. 
111-274), https://www.gpo.gov/fdsys/pkg/PLAW-111publ274/pdf/PLAW-111publ274.pdf).
    Form FDA 3500B evolved from several iterations of draft versions, 
with input from human factors experts, from other regulatory agencies, 
and with extensive input from consumer advocacy groups and the general 
public. Form FDA 3500B may be used to report to the Agency adverse 
events, product problems, and product use errors. The form is provided 
in both paper and electronic formats. Reporters may mail or Fax paper 
forms to the Agency (a fillable PDF version of the form is available at 
https://www.fda.gov/downloads/AboutFDA/ReportsManualsForms/Forms/UCM349464.pdf) or electronically submit a report via the MedWatch 
Online Voluntary Reporting Form (https://www.accessdata.fda.gov/scripts/medwatch/, approved under OMB control number 0910-0645). 
Reporting is supported for drugs, non-vaccine biologicals, medical 
devices, special nutritional products, cosmetics, and non-prescription 
OTC human drug products marketed without an approved application. The 
paper form may also be used to submit reports about tobacco products 
and dietary supplements. Electronic reports for tobacco products and 
dietary supplements may be submitted to the Agency via an online 
submission route called the Safety Reporting Portal (https://www.safetyreporting.hhs.gov/, approved under OMB control number 0910-
0645).

II. Proposed Modification to Existing Forms FDA 3500, 3500A, and 3500B

A. General Changes

    The proposed modifications to Form FDA 3500 and Form FDA 3500A 
reflect changes that will bring the form into conformity, since the 
previous OMB authorization in 2015, with current regulations, rules, 
and guidances and fall into three categories: (1) Regulatory driven 
revisions, (2) work improvements for the Center, and (3) report 
processing improvements. We also welcome comments about translation of 
Form FDA 3500B (consumer) into Spanish and other languages. Lastly, 
formatting modifications are being proposed to several fields to 
enhance the quality, utility, and clarity of the information.

B. Changes Proposed for Form FDA 3500

    In section A, we are revising the heading of A3 to ``Current 
Gender'' followed by check boxes next to the following options 
``Female'', ``Male'', ``Intersex'', ``Transgender'', ``Prefer not to 
disclose.''
    In section B, we are revising B1 to ``Type of Report (check all 
that apply)''. In section B2, we are removing ``(Devices)'' from the 
last option. We are also splitting section B6 into two

[[Page 46169]]

questions: ``B6.a. Relevant Test (please included dates)'' and ``B6.b. 
Relevant Laboratory Data (please included dates).''
    In section C, we are adding question C2 ``Do you have a picture of 
the product?''
    In section D1, we are adding the question ``Does this report 
involve cosmetics, dietary supplements or food?'' followed by a 
checkbox for ``Yes.'' In section D4, we are adding the question ``Is 
therapy still on-going?'' This question is important for 
pharmacovigilance and the current form does not allow the reporter to 
be specific. The current form does not allow the reporter to be 
specific. It is proposed to combine boxes D6 and D7 and change the 
title to ``Product Type'' (check all that apply).
    In section E, we are adding question E9 ``Was this device serviced 
by a third-party servicer?'' followed by a checkbox for ``Yes'' and a 
checkbox for ``No.''

C. Changes Proposed for Form FDA 3500A

    In section A, we are revising the heading of A3 to ``Current 
Gender'' followed by check boxes next to the options ``Female'', 
``Male'', ``Intersex'', ``Transgender'', ``Prefer not to disclose''.
    In section B, we are revising the heading for BI to now read ``Type 
of Report (check all that apply)''. In section B2, we are removing 
``(Devices)'' from the last option. Section B6 is being split into two 
questions: ``B6.a. Relevant Test (please include dates)'' and ``B6.b. 
Relevant Laboratory Data (please include dates),''
    In section C, we are combining boxes C6 and C7 and changing the 
title to ``Product Type'' (check all that apply).
    In section D, we are adding a new question ``Was this device 
serviced by a third party?'' followed by a checkbox for ``Yes'' and a 
checkbox for ``No.''
    In section F, we are changing the revising the heading of F10 to 
``Adverse Event Problem'' and splitting the ``Patient Code'' box into 
two fields entitled ``Patient Outcome Code'' and ``Patient Severity 
Code.'' We are also splitting the ``Device Code'' field into two fields 
entitled ``Device Code'' and ``Component Code.''
    In section G, question G1 will now include ``or Compounding 
Outsourcing Facility'' after (and Manufacturing Site for Devices.)'' In 
section G5, we are adding two new options entitled ``PreANDA'' and 
``Compounded Product'' followed by a check box for ``Yes,'' and making 
consistent changes within section G6 by replacing ``If IND,'' to ``Give 
Protocol #.''
    In section H1, we are adding a check box to indicate whether a 
summary report is included followed by a field in which to indicate 
``Number of Events Summarized'' and an open field in which to add text. 
We are renaming section H6 to ``Adverse Event Problem'' and splitting 
``Patient Code'' into two fields entitled ``Patient Outcome Code'' and 
``Patient Severity Code.'' We are also splitting ``Device Code'' into 
two fields entitled ``Device Code'' and ``Component Code.'' In section 
H6, we are renaming the headings as follows: (1) ``Method'' to ``Type 
of Investigation'' (2) ``Results'' to ``Investigation Findings'' and 
(3) ``Conclusions'' to ``Investigation Conclusion.'' Finally, H10 is 
becoming a field entitled ``Additional Manufacturer Narrative,'' and we 
are adding field H11 entitled ``Corrected Data.''

D. Changes Proposed for Form FDA 3500B

    On page 1, we are removing the text ``nutrition products, such as 
vitamins and minerals, herbal remedies, infant formulas, and medical 
foods.'' We are also going to number each of the questions included.
    In section A, for the question ``Did any of the following happen?'' 
we are removing ``Devices)'' from the last option. We are also revising 
the question ``List any relevant tests or laboratory data if you know 
them. (Include dates)'' as two separate questions: ``List any relevant 
tests (Include dates)''; and ``List any relevant laboratory data 
(Include dates)'' with corresponding date fields for ``relevant tests'' 
and ``laboratory data.''
    In section B, we are asking whether respondents have a picture of 
the product. Also in section B, we are adding the questions ``Does this 
report involve cosmetics, dietary supplements, or food?'' and ``Is 
therapy still on-going?'' These questions pertain to pharmacovigilance 
and the current form does not allow for such specificity. We are also 
adding the question, ``Was the product compounded by a pharmacy or an 
outsourcing facility?'' Following the question, ``Is the Product 
Compounded?'' we are adding a check box for ``Yes'' and a checkbox for 
``No.'' We are also adding checkboxes within the field ``Product Type 
(check all that apply)'' to correspond with selections for ``Over-the-
Counter, Generic and Biosimilar.'' Finally, we are revising ``Name of 
the . . .'' to ``Name(s) of the . . .'' for clarity.
    In section C, we are separating ``Other identifying information'' 
into two fields; hoping this improves reporting. New fields will be 
entitled (1) ``Model number'' (2) ``Catalog number'' (3) ``Lot number'' 
(4) Serial number'' (5) ``UDI Number and (6) ``Expiration Date.''
    In section D we are changing the terminology from ``Sex'' to 
``Current Gender'' followed by corresponding check boxes next to the 
options ``Female'', ``Male'', ``Intersex'', ``Transgender'', ``Prefer 
not to disclose''.
    In section E, we are revising the question ``If you do NOT want 
your identity disclosed to the manufacturer, place an `X' in this 
box:'' to read ``If you do NOT want your identity disclosed to the 
manufacturer/compounder, place an `X' in this box:''

III. Public Comment

    In the Federal Register of March 16, 2018 (83 FR 11756), we 
published a 60-day notice requesting public comment on the proposed 
collection of information. A number of comments were received and are 
discussed in the following paragraphs.
    General comments included suggestions that the MedWatch program be 
better advertised to physicians and other medical healthcare 
professionals as well as patients. Also, that the forms use terminology 
more familiar to healthcare providers and consumers. For example, using 
`Medication error' or `Medication error/product use error' instead of 
`Product use error' to ensure respondents are aware that MedWatch forms 
can be used to report medication errors. Other comments suggested 
revisions that might improve or otherwise clarify instructions. 
Finally, some comments pertained to the advantages of electronic 
reporting.
    More specific comments included a suggestion to add a question to 
section A of Form FDA 3500 related to pregnancy. While we agree that 
documenting pregnancy status is important, we do not plan on adding an 
additional checkbox for pregnancy at this time. Previously (in 2005), 
we proposed adding checkboxes for both ``Product Used During 
Pregnancy'' and ``Product Used During Breast Feeding.'' However we 
received comments expressing concern that these new data fields 
introduced divergence from International Council on Harmonisation 
standards and appeared to duplicate information usually provided in the 
narrative section and in coded adverse event terms. At the same time, 
we ask readers to note that pregnancy status can be captured in field 
B7 under ``other relevant history.''
    Another comment suggested adding ``Physician Assistant'' to the 
drop down ``Occupation'' menu in section G of Form FDA 3500. We 
appreciate this

[[Page 46170]]

suggestion and will implement the revision.
    We also received comment that some users have experienced ``timing 
out'' while completing Form FDA 3500B online and requested that any 
time limit for completing online forms be extended. We were not aware 
of this issue and will investigate to see whether it relates to the 
online functionality of the form. If so, we will make the necessary 
adjustments.
    While we are especially appreciative of the comments received in 
response to our notice, we continue to welcome feedback at all times 
regarding ways we might improve the MedWatch Program and the associated 
forms. In addition to the revisions discussed previously, on our own 
initiative we are now including burden associated with written 
submissions under Sec.  329.100(c)(2) (21 CFR 329.100(c)(2)) that 
request a temporary waiver from the electronic reporting requirements 
associated with postmarket adverse drug events under section 760 of the 
FD&C Act. While we expect few such waiver requests, we retain a 
placeholder for one respondent annually, and we estimate it takes 1 
hour to complete the request.
    We therefore estimate the burden for the information collection as 
follows.

                                                     Table 1--Estimated Annual Reporting Burden \1\
--------------------------------------------------------------------------------------------------------------------------------------------------------
                                                                   Number of
 FDA center or 21 CFR section and/or FDA form      Number of     responses per   Total annual          Average burden per response          Total hours
                                                  respondents     respondent       responses
--------------------------------------------------------------------------------------------------------------------------------------------------------
Center for Biologics Evaluation and Research/
 Center for Drug Evaluation and Research:
    Form 3500.................................          14,727               1          14,727  0.66 (40 minutes).......................           9,720
    Form 3500A (Sec.  Sec.   310.305, 314.80,              599              98          58,702  1.21....................................          71,029
     314.98, 600.80, and 1271.350).
    Form 3500A (Sec.   310.305 outsourcing                  50               2             100  1.21....................................             121
     facilities).
Center for Devices and Radiological Health:
    Form 3500.................................           5,233               1           5,233  0.66 (40 minutes).......................           3,454
    Form 3500A (part 803).....................           2,277             296         673,992  1.21....................................         815,530
Center for Food Safety and Applied Nutrition:
    Form 3500.................................           1,793               1           1,793  0.66 (40 minutes).......................           1,183
    Form 3500A................................           1,659               1           1,659  1.21....................................           2,007
Center for Tobacco Products:
    Form 3500.................................              39               1              39  0.66 (40 minutes).......................              26
All Centers:
    Form 3500B................................          13,750               1         13, 750  0.46 (28 minutes).......................           6,325
Written requests for temporary waiver under                  1               1               1  1.......................................               1
 Sec.   329.100(c)(2):
                                               ---------------------------------------------------------------------------------------------------------
    Total.....................................  ..............  ..............  ..............  ........................................         909,396
--------------------------------------------------------------------------------------------------------------------------------------------------------
\1\ There are no capital costs or operating and maintenance costs associated with this collection of information.

    While we retain the currently approved estimate for the information 
collection, as noted previously we have added burden associated with 
written submissions under Sec.  329.100.

    Dated: September 4, 2018.
Leslie Kux,
Associate Commissioner for Policy.
[FR Doc. 2018-19742 Filed 9-11-18; 8:45 am]
BILLING CODE 4164-01-P


