[Federal Register Volume 65, Number 222 (Thursday, November 16, 2000)]
[Notices]
[Pages 69314-69317]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 00-29324]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. 96N-0393]


Agency Information Collection Activities; Submission for OMB 
Review; Comment Request; MedWatch: The FDA Medical Products Reporting 
Program

AGENCY: Food and Drug Administration, HHS.

[[Page 69315]]


ACTION: Notice.

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SUMMARY: The Food and Drug Administration (FDA) is announcing that the 
proposed collection of information listed below has been submitted to 
the Office of Management and Budget (OMB) for review and clearance 
under the Paperwork Reduction Act of 1995.

DATES: Submit written comments on the collection of information by 
December 18, 2000.

ADDRESSES: Submit written comments on the collection of information to 
the Office of Information and Regulatory Affairs, OMB, New Executive 
Office Bldg., 725 17th St. NW., rm. 10235, Washington, DC 20503, Attn: 
Wendy Taylor, Desk Officer for FDA.

FOR FURTHER INFORMATION CONTACT: Mark L. Pincus, Office of Information 
Resources Management (HFA-250), Food and Drug Administration, 5600 
Fishers Lane, Rockville, MD 20857, 301-827-1471.

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 (Forms FDA 
3500 and FDA 3500A) (OMB Control Number 0910-02910)--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 it is misbranded if 
it fails to bear adequate warnings, and under section 502(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 (the DSHEA) (21 U.S.C. 301), 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. Likewise for cosmetics, the act does not 
give FDA the authority to require manufacturers to register their 
cosmetic establishments, file data on ingredients, conduct safety 
testing, or report cosmetic-related injuries. Only postmarket 
surveillance allows FDA to assess cosmetic problems in the marketplace.
    To carry out its responsibilities, the agency needs to be informed 
whenever an adverse event or product problem 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 actions ranging from labeling changes to the rare product 
withdrawal. 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, 606, and 803 (21 CFR parts 310, 314, 
600, 606, and 803), specifically Secs. 310.305, 314.80, 314.98, 600.14, 
600.80, 606.170, 606.171, 803.30, 803.50, 803.53, and 803.56.
    To implement these provisions for reporting of adverse events and 
product problems with human medications, devices, and biologics, as 
well as any other products that are regulated by FDA, two very similar 
forms are used (an exception is biologic product deviation reports). 
Form FDA 3500 is used for voluntary (i.e., not mandated by law or 
regulation) reporting of adverse events and product problems by health 
professionals and the public. Form FDA 3500A is used for mandatory 
reporting (i.e., required by law or regulation). New biologic 
regulations Secs. 600.14 and 606.171 require that biologic product 
deviation reports, which are similar to drug product problem reports, 
be submitted to FDA via a different form. Reports of fatalities as a 
complication of blood collection or transfusion are reported as per 
Sec. 606.170.
    Respondents to this collection of information are health 
professionals, hospitals and other user-facilities (e.g., nursing 
homes, etc.), consumers, manufacturers of biologics, drugs and medical 
devices, and importers.

I. Use of the Voluntary Version (FDA Form 3500)

    Individual health professionals are not required by law or 
regulation to submit adverse event or product problem reports to the 
agency or the manufacturer. There is one exception. The National 
Childhood Injury Act of 1986 mandates that certain adverse events 
following immunization be reported by health care providers to the 
joint FDA/Centers for Disease Control and Prevention Vaccine Adverse 
Event Reporting System (VAERS). Vaccine reporting should be submitted 
on Form VAERS-1 (FDA).
    Hospitals are not required by Federal law or regulation to submit 
adverse event reports on medications. However, hospitals and other 
medical facilities are required by Federal law to report medical 
device-related deaths and serious injuries, biological product 
deviation reports, and reports of fatalities as a complication of blood 
collection or transfusion.
    Manufacturers of dietary supplements do not have to prove safety or 
efficacy of their products prior to marketing, nor do they have 
mandatory requirements for reporting adverse reactions to FDA. However, 
the DSHEA puts the onus on FDA to prove that a particular product is 
unsafe. Likewise for cosmetics, the act does not give FDA the authority 
to require manufacturers to register their cosmetic establishments, 
file data on ingredients, conduct safety testing, or report cosmetic-
related injuries. Only postmarket surveillance allows FDA to assess 
cosmetic problems in the marketplace. If a problem is detected, it is 
up to the agency to demonstrate that the product is harmful when used 
according to label directions or under customary conditions of use. 
Consequently, the agency is totally dependent on voluntary reporting by 
health professionals and consumers about problems with the use of 
dietary supplements and cosmetics.
    The voluntary version of the form is used to submit all adverse 
event and product problem reports not mandated by Federal law or 
regulation.

II. Use of the Mandatory Version (FDA Form 3500A)

A. Drug and Biologic Products

    In section 505(j) and 704 of the act (21 U.S.C. 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 and 314 
(drugs) and part 600 (biologics) of the Code of Federal Regulations. 
Parts 310, 314, and 600 mandate the use of the FDA Form 3500A for 
reporting to FDA on adverse events that occur with drugs and biologics. 
Blood-related fatalities are reported per Sec. 606.170.

B. Medical Device Products

    Section 519 of the act (21 U.S.C. 360i) requires manufacturers or 
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

[[Page 69316]]

may by regulation reasonably require to ensure that such devices are 
not adulterated or misbranded and to otherwise ensure its safety and 
effectiveness. Furthermore, the Safe Medical Device Act of 1990, signed 
into law on November 28, 1990, amends section 519 of the 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. FDA has codified these statutory requirements regarding 
mandatory reporting under part 803. Part 803 mandates the use of FDA 
Form 3500A for reporting to FDA on medical devices.

C. Other Products Used in Medical Therapy

    There are no mandatory requirements for the reporting of adverse 
events or product problems with products such as dietary supplements. 
However, the DSHEA puts the onus on FDA to prove that a particular 
product is unsafe. Consequently, the agency is totally dependent on 
voluntary reporting by health professionals and consumers about 
problems with the use of dietary supplements. (Most pharmaceutical 
manufacturers already use a one-page modified version of the Form FDA 
3500A where section G from the back is substituted for section D on the 
front of the form.)

D. Medical Device Baseline Information

    The Medical Device Reporting form (Form FDA 3417) relates 
specifically to the individual device and must be submitted with the 
first adverse event on that device reported via Form FDA 3500A. The 
information collected includes the basis for marketing (510(k), PMA, 
etc.), product code for the device, common name, location where 
manufactured, and other identifying information. The Health Industry 
Manufacturers Association (HIMA) first commented in 1992 on the 
redundancy of information required for the Baseline form stating that 
the information is also collected by the agency though the device 
listing process (Form FDA 2892) and through Form FDA 3500A. In 1998, 
HIMA commented again and, at the request of OMB, FDA explored revising 
Form FDA 3500A to include the information required by the Baseline form 
that is not collected through the listing process.
    In discussions with OMB it was decided that FDA would not attempt 
to revise Form FDA 3500A at this time, but would proceed with 
collecting the information required by the Baseline form as a separate 
part of the device listing process especially because some of the 
information required by the current Baseline form will be collected in 
that listing as a change in the listing regulations. Because the 
collection of registration and listing information will be through 
electronic means, the agency envisions a menu option on the Internet to 
facilitate the collection of the remainder of Baseline information.
    FDA has held stakeholder meetings and discussed the new device 
registration and listing system and using the new device and listing 
system electronic process as the vehicle for the Baseline information 
collection at those meetings.
    The agency requested comments on this proposed collection of 
information in the Federal Register of July 26, 2000 (65 FR 45988).
    FDA received comments from four interested parties, but some 
comments raised multiple concerns.
    While the comments on the proposed revisions to the form(s) were 
mainly favorable, the agency has decided to not revise either form at 
this time. This decision reflects several concerns. The financial 
burden that would be placed on sponsors and others required to report, 
and FDA if the forms underwent revision, and the availability of other 
avenues by which use of the voluntary and mandatory forms can be 
optimized, namely appropriate revision of documents related to their 
completion.
    One comment suggested more detailed instructions for completing the 
MedWatch form. The instructions for the voluntary form 3500 were 
updated and posted on the Internet in April 2000 and the instructions 
for 3500A were extensively revised and posted May 2000 (http://www.fda.gov/medwatch/report/instruc.htm). Regarding voluntary 
reporting, updated instructions for completing the 3500 form were 
posted on the MedWatch homepage in December 1998 and April 2000. They 
are available by mail/fax upon request. The revisions of both the 
voluntary and mandatory instructions for use were based on questions/
comments about adverse event/product problem reporting received by the 
agency over time. One main revision on both forms was to include 
information about reporting on reuse of medical devices labeled for 
single use.
    One comment suggested revising the March 1992 guidelines to 
incorporate MedWatch form use. FDA published a revised guidance for 
industry entitled ``Postmarketing Adverse Experience Reporting for 
Human Drug and Licensed Biological Products: Clarification of What to 
Report,'' in August 1997 (http://www.fda.gov/cder/guidance/1830fn1.pdf). In this guidance it states that the agency is still 
considering comments received in response to the proposed Federal 
Register of October 27, 1994, and recommendations recently developed by 
the International Conference on Harmonization and plans to propose 
additional amendments to its postmarketing safety reporting 
regulations. FDA also plans to prepare a single consolidated guidance 
document on this topic once the process is concluded.
    One comment suggested a FDA industry-wide assessment of consistency 
of MedWatch field use for both devices and drugs. At this time a formal 
assessment of the completion of the forms is not planned. As stated 
above, questions/comments about use of the form and reporting have been 
incorporated into the revised instructions for use for both forms. This 
issue can also be addressed in any new proposed regulations or guidance 
documents.
    One comment suggested expanding public education regarding 
postmarketing events. The MedWatch Office is in the process of 
developing educational materials, primarily for health professionals, 
to assist in the overall effort to improve the quality of MedWatch 
reports.
    One comment was made about the estimate of the ``hours per 
response.'' Because the 3500A is used for mandatory reporting subject 
to different regulations (i.e., 21 CFR 310.305, 312.32, 314.80, 600.80, 
and part 803), this estimate for reporting burden is limited to 
completing the form. Estimates of the burden placed on user-facilities, 
importers and manufacturers to investigate a report and compile the 
necessary information would be addressed in the final rules for those 
regulations.
    One comment suggested further clarification of the August 1997 
guidance for definitions of identifiable patient and reporter. This 
topic is currently being discussed in the World Health Organization's 
Council for International Organizations of Medical Sciences, Work Group 
5.
    One comment suggested focusing on new or unusual events and to 
allow reporting of known non-serious events via line listing. This same 
commenter suggested minimal data collection for known and well-
characterized cases. These comments are addressed in the August 1997 
guidance for industry entitled ``Postmarketing Adverse

[[Page 69317]]

Experience Reporting for Human Drug and Licensed Biological Products: 
Clarification of What to Report.''
    One comment suggested adding a box to the 3500A form to require 
drug manufacturers to state the date the report was forwarded to FDA. 
This is currently required for medical device reporting, but not for 
drugs and biologics. However, all manufacturers must report the date 
received by the manufacturer on form 3500A, section G4. Many large 
manufacturers have data bases that contain the date the information was 
received and the date the report was sent to FDA. As a surrogate, these 
two dates can be compared to see if the company is fulfilling its 
requirements under the regulations. The agency can use its regulatory 
discretion in deciding whether or not action is warranted in the case 
of delayed reports. What is of greater concern is the failure to report 
and that cannot be detected by adding this information to the form. 
Given that the goal is for both pharmaceutical and medical device 
industries to submit the majority of mandatory reports electronically, 
it would present a financial burden to revamp systems to accommodate a 
paper form that will be virtually obsolete in the future.
    One comment suggested a ``tick box for a 30-day report,'' for form 
3500A. At this time there is no requirement for a 30-day report.
    As both the 3500 instructions and 3500A instructions can be updated 
periodically based on questions/comments from stakeholders and 
statutory/regulatory changes, changing the forms themselves is not seen 
as necessary at this point.
    At such time it is decided to repropose revisions, FDA will consult 
all interested parties for input into the design.
    FDA estimates the burden for this collection of information as 
follows:

                                 Table 1.--Estimated Annual Reporting Burden \1\
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                                              Annual
  FDA center(s) (21   No. of respondents   frequency per     Total annual        Hours per        Total hours
    CFR section)                             response          responses         response
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CBER/CDER\2\
  Form 3500              16,198                 1            16,198                 0.5           8,099
  Form 3500A                600               455.2         273,109                 1           273,109
   (310.305, 314.80,
   314.98, and
   600.80)
CDRH\3\
  Form 3500               2,650                 1             2,650                 0.5           1,325
  Form 3500A (part        2,046                24            49,305                 1            49,305
   803)
CFSAN\4\
  Form 3500                 550                 1               550                 0.5             275
  Form 3500A                  0                 0                 0                 1                 0
  No mandatory
   requirements
Total Hours                                                                                     332,113
  Form 3500                                                                                       9,699
  Form 3500A                                                                                   322,414
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\1\ There are no capital costs or operating and maintenance costs associated with this collection of
  information.
\2\ Center for Biologics Evaluation and Research/Center for Drug Evaluation and Research.
\3\ Center for Devices and Radiological Health.
\4\ Center for Food Safety and Applied Nutrition.
FDA Form 3500 is for voluntary reporting. FDA Form 3500A is for mandatory reporting.
The figures shown in table 1 of this document are based on actual calendar year 1999 reports and respondents.

    As more medical products are approved by the FDA and marketed, and 
as knowledge increases regarding the importance of notifying FDA when 
adverse events and product problems are observed, it is expected that 
more voluntary reports will be submitted. Conversely, with the current 
plans for increasing electronic submissions it is expected that the 
number of mandatory reports will decrease.

    Dated: November 9, 2000.
Margaret M. Dotzel,
Associate Commissioner for Policy.
[FR Doc. 00-29324 Filed 11-15-00; 8:45 am]
BILLING CODE 4160-01-F