[Federal Register: August 16, 2005 (Volume 70, Number 157)]
[Page 48157-48160]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]



Food and Drug Administration

[Docket No. 2004N-0535]

Agency Information Collection Activities; Submission for Office 
of Management and Budget Review; Comment Request; MedWatch: 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 
September 15, 2005.

ADDRESSES: OMB is still experiencing significant delays in the regular 
mail, including first class and express mail, and messenger deliveries 
are not being accepted. 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: Fumie 
Yokota, Desk Officer for FDA, FAX: 202-395-6974.

FOR FURTHER INFORMATION CONTACT: Karen L. Nelson, Office of Management 
Programs (HFA-250), Food and Drug Administration, 5600 Fishers Lane, 
Rockville, MD 20857, 301-827-1482.

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: FDA Medical Products Reporting Program, Form FDA 3500 and 
Form FDA 3500A--(OMB Control Number 0910-0291)--Extension

    Under sections 505, 512, 513, 515, and 903 of the Federal Food, 
Drug, and Cosmetic Act (the act) (21 U.S.C. 355, 360b, 360c, 360e, and 
393), and section 351 of the Public Health Service Act (42 U.S.C. 262), 
FDA has the responsibility to ensure the safety and effectiveness of 
drugs, biologics, and devices. Under section 502(a) of the act (21 
U.S.C. 352(a)), a drug or device is misbranded if its labeling is false 
or misleading. Under section 502(f)(1) of the act (21 U.S.C. 
352(f)(1)), it is misbranded if it fails to bear adequate warnings, and 
under section 502(j) of the act (21 U.S.C.

[[Page 48158]]

352(j)), it is misbranded if it is dangerous to health when used as 
directed in its labeling.
    Under section 4 of the Dietary Supplement Health and Education Act 
of 1994 (DSHEA) (21 U.S.C. 341), section 402 of the act (21 U.S.C. 342) 
is amended so that FDA must bear the burden of proof to show a dietary 
supplement is unsafe.
    To carry out its responsibilities, the agency needs to be informed 
whenever an adverse event, product problem, or error with use of a 
medication or device occurs. Only if FDA is provided with such 
information will the agency be able to evaluate the risk, if any, 
associated with the product, and take whatever action is necessary to 
reduce or eliminate the public's exposure to the risk through 
regulatory action. To ensure the marketing of safe and effective 
products, certain adverse events must be reported. Requirements 
regarding mandatory reporting of adverse events or product problems 
have been codified in parts 310, 314, 600, 803, and 1271 (21 CFR parts 
310, 314, 600, 803, and 1271), specifically Sec. Sec.  310.305, 314.80, 
314.98, 314.540, 600.80, 803.30, 803.50, 803.53, 803.56, and 
    To implement these provisions for reporting of adverse events, 
product problems, and medication/device use errors for FDA regulated 
products such as medications, devices, biologics, including human 
cells, tissues, and cellular and tissue-based products (HCT/Ps), 
special nutritional products, and cosmetics, as well as any other 
products that are regulated by FDA, two forms are available from the 
agency. Form FDA 3500 may be used for voluntary (i.e., not mandated by 
law or regulation) reporting by healthcare professionals and the 
public. Form FDA 3500A is used for mandatory reporting (i.e., required 
by law or regulation).
    Respondents to this collection of information are healthcare 
professionals, hospitals and other user facilities (e.g., nursing 
homes, etc.), consumers, manufacturers of biological and drug products 
or medical devices, and importers.

II. Use of Form FDA 3500 (Voluntary Version)

    The voluntary version of the form is used 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 certain adverse reactions 
following immunization with vaccines as mandated by the National 
Childhood Vaccine Injury Act of 1986. Those mandatory reports are not 
submitted to FDA on Form FDA 3500 or Form FDA 3500A, but are submitted 
to the joint FDA/Centers for Disease Control and Prevention Vaccines 
Adverse Event Reporting System (VAERS) on the VAERS-1 form. (See http://frwebgate.access.gpo.gov/cgi-bin/leaving.cgi?from=leavingFR.html&log=linklog&to=http://www.vaers.hhs.gov.
) (FDA has verified the Web site addresses, but we 

are not responsible for subsequent changes to the nonFDA Web sites 
after this document publishes in the Federal Register.)
    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.
    Manufacturers of dietary supplements do not have mandatory 
requirements for reporting adverse reactions to FDA. DSHEA puts the 
responsibility on FDA to prove that a particular product is unsafe. The 
agency depends on the voluntary reporting by health professionals and 
consumers of suspected adverse events associated with the use of 
dietary supplements.

III. Use of Form FDA 3500A (Mandatory Version)

A. Drug and Biologic Products

    In sections 505(j) and 704 of the act (21 U.S.C. 355(j) and 374), 
Congress has required that important safety information relating to all 
human prescription 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 act (21 U.S.C. 372) authorizes 
investigational powers to FDA for enforcement of the act. These 
statutory requirements regarding mandatory reporting have been codified 
by FDA under parts 310 (New Drugs) and 314 (Applications for FDA 
Approval to Market a New Drug), 600 (Biological Products: General), and 
1271 (Human Cells, Tissues, and Cellular and Tissue-Based Products). 
Parts 310, 314, 600, and 1271 mandate the use of Form FDA 3500A for 
reporting to FDA adverse events that occur with drugs and biologics.

B. Medical Device Products

    Section 519 of the 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 require to 
assure that such devices are not adulterated or misbranded and to 
otherwise assure their safety and effectiveness.
    The Safe Medical Device Act of 1990, signed into law on November 
28, 1990, amends section 519 of the act (21 U.S.C. 360i). 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), 
Public Law 107-250, signed into law October 26, 2002, amended section 
519 of the act. The amendment (section 303 of MDUFMA) requires 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.

IV. Proposed Modifications to Forms

    The proposed modifications to Form FDA 3500 and Form FDA 3500A 
reflect changes that will bring the forms into conformation with 
current regulations, rules, and guidances. Modifications were also made 
to better reflect the range of reportable products and language was 
changed slightly to provide clarity. The changes should allow reporters 
to better utilize available space for data entry and offer voluntary 
reporters the opportunity to better characterize the suspected adverse 
event, product problem or error, and provide better quality safety-
related data for agency evaluation.
    FDA estimates the burden for completing the forms for this 
collection of information as follows:

[[Page 48159]]

                                                     Table 1.--Estimated Annual Reporting Burden\1\
                                                               No. of        Annual Frequency      Total Annual         Hours per
             FDA Center(s) (21 CFR Section)                 Respondents        per Response         Responses           Response          Total Hours
Center for Biologic Evaluation and Research/Center for Drug Evaluation and Research
Form FDA 3500\2\                                                    23,867                 1               23,867                 0.6             14,320
Form FDA 3500A (310.305, 314.80, 314.98, and 600.80)                   600               579.9            401,390                 1.1            441,529
Center for Devices and Radiological Health
Form FDA 3500\2\                                                     3,717                 1                3,717                 0.6              2,230
Form FDA 3500A (part 803)\3\                                         1,919                40               76,203                 1.1             83,823
Center for Food Safety and Applied Nutrition
Form FDA 3500\2\                                                       665                 1                  665                 0.6                399
Form FDA 3500A (No mandatory requirements)\3\                            0                 0                    0                 1.1                  0
Form FDA 3500\2\                                                                                                                                  16,949
Form FDA 3500A\3\                                                                                                                                525,352
Total Hours                                                                                                                                      542,301
\1\ There are no capital costs or operating and maintenance costs associated with this collection of information.
\2\ Form FDA 3500 is for voluntary reporting.
\3\ Form FDA 3500A is for mandatory reporting.
(NOTE: The figures shown in table 1 are based on actual calendar year 2004 reports and respondents.

V. Agency Response to Comments

    In the Federal Register of December 27, 2004 (69 FR 77256), FDA 
published a 60-day notice requesting public comment on the information 
collection provisions. FDA received several comments; the majority 
addressed revisions to Form FDA 3500A.
    Several pharmaceutical manufacturers expressed concern over FDA's 
revision of mandatory Form FDA 3500A since FDA encourages electronic 
submission of postmarketing adverse event reports, and it would be an 
unfair burden to manufacturers who submit electronically to expend 
resources to change the form which would be used only in times of rare 
network or server outages. FDA disagrees with this comment. As 
described in a May 2001 draft guidance entitled ``Providing Regulatory 
Submissions in Electronic Format Postmarketing Expedited Safety 
Reports'', manufacturers can send individual case safety reports 
(ICSRs) to FDA using either FDA's electronic data interchange (EDI) 
gateway or physical media (such as CD-ROM or digital tape). If the EDI 
gateway is not functional, regulatory requirements can be met by 
submitting ICSRs on physical media.
    A number of manufacturers commented that certain sections of 
proposed Form FDA 3500A were based on proposed rules, regulations, and 
guidances. They noted that considerable resources would be required to 
modify computer systems and processes, and changes to the form should 
be based on current rules, regulations, and guidances. Likewise, such 
changes should be consistent with current International Conference on 
Harmonization (ICH) guidelines. FDA agrees with these comments and has 
based the final revised Form FDA 3500A on current rules, regulations, 
and guidances to the extent possible. Proposed reformatting of Form FDA 
3500A has also been minimized based on these comments. In addition, to 
allow mandatory reporters time to make the necessary changes to their 
computer systems and processes to conform to the revised Form FDA 3500A 
, FDA is granting a grace period of 1 year. During this transition 
period FDA will accept both the newly effective Form FDA 3500A and the 
prior version of the form.
    Device manufacturers commented that there were unnecessary changes 
made to the form pertaining only to device reporting. FDA agrees and 
has minimally altered the device sections of the final forms. FDA 
additionally recognizes the burden this places on device manufacturers 
as they were recently required to make computer and process changes 
based on the modified Form FDA 3500A as mandated by MDUFMA.
    Some comments noted that FDA underestimated the burden of the 
proposed collection of information, only capturing time required to 
complete the form and not capturing the significant resources required 
to modify and validate the forms. One drug manufacturer estimated that 
50 to 60 hours per computerized system would be required to modify and 
validate the changes to the form. FDA acknowledges these comments and 
has made an effort to modify Form FDA 3500A to the minimum extent 
possible to conform with current rules, regulations, and guidances in 
order to minimize this burden to industry.
    Several comments noted that FDA did not include instructions to 
revised Form FDA 3500 and Form FDA 3500A, which resulted in a lack of 
clarity in modified sections and lack of definition regarding newly 
added terminology. FDA acknowledges these comments. Both the previous 
and newly revised Form FDA 3500A along with the newly revised voluntary 
Form FDA 3500, with instructions for both forms, will be made available 
upon OMB approval on FDA's MedWatch Web site at http://frwebgate.access.gpo.gov/cgi-bin/leaving.cgi?from=leavingFR.html&log=linklog&to=http://www.fda.gov/medwatch/getforms.htm

    One comment requested consistency in formatting of dates throughout 
both forms. FDA agrees and has conformed to a mm/dd/yyyy format 
throughout both forms.
    FDA proposed several changes to section B.2 (Outcomes Attributed to 
Adverse Event) of both forms. A number of comments were received 
regarding this proposal. The ``Not Serious'' and ``No Harm'' checkboxes 
elicited comments that clarification was required regarding when these 
boxes would be used, and that these boxes do not conform to any current 
rules, regulations, or guidances, including

[[Page 48160]]

current ICH guidances. FDA agrees with these comments and the ``Not 
Serious'' and ``No Harm'' checkboxes do not appear on the final Form 
FDA 3500 and Form FDA 3500A. Another proposed checkbox was ``Important 
Medical Events''. This checkbox has been revised on the final Form FDA 
3500 and Form FDA 3500A to ``Other Serious (Important Medical 
Events)''. This new terminology is consistent with the definition of 
``Serious'' in 21 CFR 310.305, 312.32, 314.80, and 600.80 as well as 
ICH E2A guidelines. In addition, the outcome ``Required Intervention to 
Prevent Permanent Impairment/Damage'' has been revised, adding 
``(devices)'' at the end of the term. Additional detail has been 
provided in the revised instructions to provide more clarity for the 
use of section B.2 of both forms.
    In section B.5 of both forms, the proposed checkboxes ``Product 
Used During Pregnancy'' and ``Product Used During Breast Feeding'' 
produced concern as these new data fields introduce divergence from ICH 
standards and appear to duplicate information that is usually provided 
in the narrative section and in coded adverse event terms. FDA agrees 
and has not included these checkboxes in the final forms. As a result, 
the term ``Pregnancy'' has been returned to the examples in section B.7 
(Other Relevant History) on both Form FDA 3500 and Form FDA 3500A.
    A few comments noted the removal of the term ``if known'' from 
several fields of the forms and questioned this action as a new 
requirement for these data. The final forms do not contain the term 
``if known'' in any of the fields for reasons of form consistency. This 
should not be interpreted as a new requirement. If information is not 
known for any of the fields, they should be left blank. This is 
reflected in the revised instructions.
    Several comments questioned the addition of the Unique Identifier 
Number (Unique ID) to proposed section D.9 of both forms. Unique ID is 
required under Sec.  1271.350 for reporting of adverse events for HCT/
    One comment recommended the addition of ``Solicited'' and 
``Spontaneous'' checkboxes to Form FDA 3500A. FDA has not accepted this 
recommendation. As described in an August 1997 guidance for industry 
entitled ``Postmarketing Adverse Experience Reporting for Human Drug 
and Licensed Biological Products: Clarification of What to Report,'' 
information concerning potential adverse experiences derived during 
planned contacts and active solicitation of information from patients 
should be handled as safety information obtained from a postmarketing 
study. Section G of the previous and revised Form FDA 3500A contains a 
checkbox for ``Study'' which captures such information.
    One comment requested that FDA include information on drug name, 
dose, frequency, route, dates of diagnosis for use, and event abated/
reappeared after reintroduction on one line of Form FDA 3500 and Form 
FDA 3500A. FDA disagrees since these changes would decrease form 
clarity and would require costly and unnecessary computer and process 
    One comment noted that the MedWatch program needs to do the 
following: (1) Enhance the quality, utility, and clarity of information 
to be collected; (2) data entry accuracy needs to be improved; and (3) 
the public version of the adverse events database needs to be posted in 
a timely manner, and FDA needs to vigorously enforce mandatory 
reporting requirements. FDA acknowledges these comments regarding FDA 
programs and processes. However, the comment did not suggest specific 
changes to Form FDA 3500 or Form FDA 3500A .
    In the final versions of Form FDA 3500 and Form FDA 3500A, there 
are some differences. FDA proposed adding two checkboxes to section 
B.1: ``Product Use Error'' and ``Product Switch''. Since there is 
currently no requirement to report medication, device, or other 
regulated product errors, these boxes do not appear on the final 
version of Form FDA 3500A . However, ``Product Use Error'' will be 
included on the voluntary Form FDA 3500, as the agency has become aware 
that voluntary reporters who wish to submit medication and other 
product use errors to FDA are not certain that Form FDA 3500 can be 
used for this purpose. FDA encourages voluntary reporting of product 
use errors.
    The ``Product Switch'' checkbox does not appear on the final Form 
FDA 3500A , however, a revised checkbox ``Problem with different 
manufacturer of same medicine,'' does appear on Form FDA 3500 to enable 
voluntary reporters to more clearly submit reports directly to FDA that 
involve adverse events or product problems related to brand-to-generic, 
generic-to-brand, one generic to another generic, or other therapy 
changes relating to the same active ingredient produced by different 
    FDA proposed reformatting changes in sections A and D of both forms 
to conserve space on the forms. These changes do not appear on the 
final Form FDA 3500A; however, section D (Suspect Product(s)) of 
revised Form FDA 3500 is modified. FDA believes the collection of data 
in specific boxes for dose/amount, frequency, and route increases 
clarity and enhances the likelihood that these data would be obtained 
from consumers and healthcare professionals who voluntarily submit 
reports directly to FDA.
    Several comments were received on new section C (Product 
Availability). Pharmaceutical manufacturers expressed concern that the 
practice of obtaining, storing, and analyzing returned products would 
significantly impact their working practice and goes beyond current 
regulations and guidances. FDA agrees with these comments and the 
``Product Availability'' question has been returned to the ``Suspect 
Medical Device'' section of Form FDA 3500A . However, the revised 
voluntary Form FDA 3500 contains the new section C, to enable FDA to 
collect such information particularly for products that currently do 
not have mandatory adverse event reporting requirements, such as 
special nutritional products and cosmetics.

    Dated: August 9, 2005.
Jeffrey Shuren,
Assistant Commissioner for Policy.
[FR Doc. 05-16141 Filed 8-15-05; 8:45 am]