[Federal Register: August 29, 2000 (Volume 65, Number 168)]
[Proposed Rules]
[Page 52376-52391]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr29au00-34]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
21 CFR Part 822
[Docket No. 00N-1367]
Postmarket Surveillance
AGENCY: Food and Drug Administration, HHS.
ACTION: Proposed rule.
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SUMMARY: The Food and Drug Administration (FDA) is proposing to
implement the postmarket surveillance (PS) provisions of the Federal
Food, Drug, and Cosmetic Act (the act), as amended by the FDA
Modernization Act of 1997 (FDAMA). The purpose of this proposed rule is
to provide for the collection of useful data or other information
necessary to protect the public health and to provide safety and
effectiveness information about devices.
DATES: Submit written comments on the proposed rule by November 27,
2000. See section III of this document for the proposed effective date
of a final rule based on this document. Submit written comments
regarding the information collection by September 28, 2000.
ADDRESSES: Submit written comments on the proposed rule to the Dockets
Management Branch (HFA-305), Food and Drug Administration, 5630 Fishers
Lane, rm. 1061, Rockville, MD 20852. Submit electronic comments and
other data to http://frwebgate.access.gpo.gov/cgi-bin/leaving.cgi?from=leavingFR.html&log=linklog&to=http://www.accessdata.fda.gov/scripts/oc/dockets/comments/commentdocket.cfm. For other information about filing comments
electronically, see the SUPPLEMENTARY INFORMATION section for
information on electronic access and filing address. Submit written
comments on the information collection to the Office of Information and
Regulatory Affairs, OMB, New Executive Office Bldg., 725 17th St. NW.,
rm. 10235, Washington,
[[Page 52377]]
DC 20503, Attn: Wendy Taylor, Desk Officer for FDA.
FOR FURTHER INFORMATION CONTACT: David L. Daly, Center for Devices and
Radiological Health (HFZ-510), Food and Drug Administration, 1350
Piccard Dr., Rockville, MD 20850, 301-594-3060.
SUPPLEMENTARY INFORMATION:
Table of Contents
I. What Is the Background of This Rulemaking?
A. Legislative History
B. Legal Authority
II. What Are the Contents of this Proposed Rule?
A. Organization and Format
B. General
C. Notification
D. Postmarket Surveillance Plan
E. FDA Review and Action
F. Responsibilities of Manufacturers
G. Waivers and Exemptions
H. Records and Reports
III. When Will the Regulation be Effective?
IV. What Is the Environmental Impact of This Regulation?
V. What Is the Economic Impact of This Regulation?
A. Introduction
B. Objectives of the Proposed Rule
C. Risk Assessment/Baseline Conditions
D. Cost of Postmarket Surveillance
E. Design Costs
F. Costs of Data Collection
1. Costs for Primary Data Collection
2. Costs for Secondary Data Collection
3. Costs of Conducting Literature Searches
G. Costs of Data Analysis, Reporting, and Recordkeeping
H. Total Industry Costs of Postmarket Surveillance
I. Costs to FDA for Oversight and Review
J. Total Annual Costs of Postmarket Surveillance
K. Benefits of the Proposed Rule
L. Chronology of Historical Event
M. Postmarket Surveillance and Risk Reduction
N. Value of Avoided Mortality
O. Frequency of Adverse Events
P. Annual Benefits of the Proposed Rule
Q. Annual Costs and Benefits of the Proposed Rule
R. Small Business Analysis/Initial Regulatory Flexibility
Analysis
S. Description of Impact
T. Analysis of Alternatives
U. Ensuring Small Entity Participation in Rulemaking
VI. Conclusions
VII. How Can I Comment on This Proposed Rule?
A. Electronic Access and Filing Address
B. Written Comments
VIII. How Does This Regulation Comply With the Paperwork Reduction
Act of 1995?
I. What Is the Background of This Rulemaking?
The act (21 U.S.C. 301 et seq.) was amended by the Medical Device
Amendments of 1976 (Public Law 94-295) to give FDA broad authority over
medical devices. Other laws affecting FDA's device authority under the
act include the Safe Medical Devices Act of 1990 (the SMDA) (Public Law
101-629), the Medical Device Amendments of 1992 (MDA) (Public Law 102-
300), and FDAMA (Public Law 105-115). The SMDA established a new
provision, section 522 of the Federal Food, Drug, and Cosmetic Act (the
act) (21 U.S.C. 360l), which was later modified by the MDA and FDAMA.
This section gives FDA the authority to require manufacturers of
certain medical devices to conduct postmarket surveillance. This
surveillance allows for identification of potential problems with
medical devices by collecting useful data that can reveal unforeseen
adverse events or other information necessary to protect the public
health.
FDA's decision to approve or clear a particular device is
ordinarily based on limited premarket data. Even when there are
premarket clinical studies, those studies typically can detect only
those adverse events that are relatively frequent. PS studies can allow
FDA and manufacturers to identify less common, but potentially life-
threatening, device problems that were not evident during premarket
development, or were noted as a potential concern that did not warrant
keeping the product from reaching the market. PS establishes a way to
evaluate such relatively rare events and to identify actions that may
minimize patient risk, such as training, labeling, or design
modification.
The act provides that FDA may require a manufacturer to conduct PS
of a class II or class III device if: (1) Failure of the device would
be reasonably likely to have serious adverse health consequences, (2)
the device is intended to be implanted in the human body for more than
1 year, or (3) the device is intended to be life-sustaining or life-
supporting and is used outside a device user facility.
A. Legislative History
Congress first granted FDA the authority to require that
manufacturers of certain medical devices conduct PS with the enactment
of the SMDA. They later modified this authority in FDAMA, allowing the
agency more discretion in imposing PS and establishing a time limit for
prospective surveillance, but leaving intact the basic authority.
The legislative history of the SMDA makes clear that the authority
granted FDA under section 522 of the act to require PS of certain
devices is a flexible authority that is intended to enable the agency
to order manufacturers to collect data about unforeseen adverse events
and other information to protect the public health. See, e.g., section
522(a) of the act (listing types of devices covered by the
requirement); H. Rept. 808, 101st Cong., 2d sess., p. 32, 1990; S.
Rept. 513, 101st Cong., 2d sess., p. 42, 1990.
Many problems or risks that may occur after a device is marketed
cannot be detected before the device enters commerce. For a substantial
majority of devices, FDA sees no clinical data before the device is
commercially distributed. Section 522 of the act allows for monitoring
of the earliest experience with a device once it is distributed in the
general population under actual use conditions. In discussing the
requirements in section 522 of the act, the House Report states that
``premarket approval cannot detect all possible problems which may
occur after a device is marketed. The Committee, therefore, expects
that implants and other devices critical to human health will be
subject to postmarket surveillance for some appropriate period of time
after they are first marketed.'' (H. Rept. 808, 101st Cong., 2d sess.,
p. 32, 1990).
The legislative history of the SMDA also notes weaknesses in other
PS mechanisms. During passage of the SMDA, the U.S. Senate observed
that the General Accounting Office (GAO) and the Office of Technology
Assessment had found that reporting to FDA of potentially serious
device hazards was incomplete and untimely for certain device-related
injuries and malfunctions, despite FDA's mandatory medical device
reporting (MDR) system. This finding was confirmed during congressional
hearings. (S. Rept. 513, 101st Cong. 2d sess., p. 15, 1990.)
Although reports of device-related problems increased following the
issuance of the MDR regulation (49 FR 36325, September 14, 1984), GAO
found apparent under-reporting of device-related reportable events and
that many firms subject to the regulation were unaware of their
obligation to report device-related deaths, serious injuries, and
malfunctions to FDA. GAO reported that the more serious the event, the
less likely it was to be reported. GAO found that only 50 percent of
class I recalls, the recall classification associated with device-
related serious adverse health consequences or death, were preceded by
MDR's. (PEMD-89-10, February 1989.)
In addition to the under-reporting of device-related reportable
events by manufacturers, GAO concluded that problems existed with the
timely receipt of information. For example, information from
legislative hearings
[[Page 52378]]
and elsewhere shows that the manufacturer of the Bjork-Shiley 60-degree
Convexo-Concave heart valve had knowledge of unexpected device failures
and deficiencies in its manufacturing process. FDA did not receive
timely information necessary to initiate regulatory actions promptly to
protect the public or to inform those persons implanted with the heart
valve of what measures should be taken to minimize their risk.
GAO also documented significant weaknesses in FDA's information
gathering ability and its followup mechanisms, once information is
received. The legislative history indicated a concern that FDA had not
used its postmarket device authorities under section 518 of the act (21
U.S.C. 360h). These authorities empower the agency to order a
notification to persons subject to a risk, and to order repair or
replacement of, or reimbursement for devices. Congress attributed the
agency's failure to use its authority under section 518 of the act to
the agency's reluctance to assert this authority and to a weak
information base that did not support aggressive regulatory action.
To address these concerns, the SMDA added a number of very
important postmarket authorities to FDA's existing MDR authority,
including authority to require PS for certain types of devices. In
addition, the SMDA required the device industry to notify FDA of
certain corrective actions, to track certain devices from the place of
manufacture through the distribution chain and to the ultimate
consumer, to cease distribution of a device and to notify users to
cease use of the device, and to certify the number of MDR reports
submitted.
In practice, the provision for mandatory surveillance contained in
the SMDA was so broadly worded that it caused uncertainty about the
identity of devices subject to the requirement. There was also concern
that the provision for mandatory surveillance could authorize studies
of indeterminate duration for devices. To address these concerns, FDAMA
amended section 522 of the act to repeal mandatory surveillance, to set
a presumptive limit of 3 years on studies, and to provide FDA with
broad discretion to implement PS on a case-by-case basis.
B. Legal Authority
Section 522 of the act gives the agency authority to require PS of
certain devices. Other provisions of the act empower FDA to implement
the agency's PS authority and to monitor and enforce compliance with
section 522 of the act.
Section 502(t)(3) of the act (21 U.S.C. 352(t)(3)) provides that
noncompliance with requirements imposed under section 522 of the act
will result in the misbranding of the device that was subject to PS.
Section 301 of the act (21 U.S.C. 331) makes several actions involving
misbranded devices prohibited acts, and section 301(q) specifies that
noncompliance with PS and submission of false reports related to PS are
prohibited acts. FDA may initiate seizure of a misbranded device under
section 304 of the act (21 U.S.C. 334), and may seek injunctive,
criminal, and civil relief under sections 302 and 303 of the act (21
U.S.C. 332 and 333) against individuals who commit prohibited acts.
Section 519(a) of the act (21 U.S.C. 360i(a)) gives FDA authority
to issue reporting and recordkeeping requirements necessary to show a
product is not misbranded. The agency is proposing to require reports
and records to demonstrate that devices subject to surveillance orders
comply with them and are not misbranded under 502(t) of the act.
FDA's general authority to inspect entities subject to section 522
of the act orders comes from section 704(a) of the act (21 U.S.C.
374(a)). Section 704(e) of the act authorizes the agency to inspect
records required under section 519(a) of the act, including PS records
that would be required by a final rule based on this proposed rule.
II. What Are the Contents of This Proposed Rule?
A. Organization and Format
The Presidential Memorandum on Plain Language issued on June 1,
1998, directed the agency to ensure that all of its documents are clear
and easy to read. Part of achieving that goal involves having readers
of a regulation feel that it is speaking directly to them. Therefore,
the agency has attempted to incorporate plain language concepts through
the use of pronouns and other plain language in this proposed rule as
much as possible.
We have also organized this proposed rule to make information
easier to find by grouping related sections within subparts and placing
them under unnumbered, centered headings. Section headings are phrased
as questions that readers, especially anyone subject to a PS order,
might ask, and we have incorporated first-person personal pronouns into
these headings. For example, the heading of proposed Sec. 822.14 is,
``May I reference information previously submitted instead of
submitting it again?'' The text of each section contains the answer to
the question posed in the heading. Frequently, the answer is stated in
terms of what ``you'' (the reader) must do. For example, the answer to
``May I reference information previously submitted instead of
submitting it again?'' is, ``Yes, you may reference information that
you have submitted in premarket submissions as well as other postmarket
surveillance submissions. You must specify the information to be
incorporated and the document number and pages where the information is
located.''
We have tried to make each section of the proposed rule easy to
understand by using clear and simple language rather than jargon,
keeping sentences short, and using active voice rather than passive
voice whenever possible. We would like your comments on how effectively
we have used plain language, the organization and format of the
proposed rule, and whether these have made the document clear and easy
to read.
B. General
We are proposing this regulation to implement section 522 of the
act, as amended by FDAMA. If a manufacturer fails to comply with
requirements that FDA orders under section 522 of the act and this
regulation, the device subject to the order is misbranded. In addition,
the manufacturer would be committing a prohibited act under section
301(q)(1)(C) of the act by failing to comply with PS requirements.
The proposed regulation is intended to ensure that useful data or
other information will be collected to address public health issues or
questions related to the safety or effectiveness of devices for which
the agency has issued PS orders. These issues or questions may include,
among other things, the identification of unanticipated adverse events.
They also may include the rate of known adverse events as the
indications or conditions for use of the device change, e.g., from
professional to over the counter use. We believe that the manufacturer
is most likely to collect useful information through clear
identification of the surveillance question(s) or issue(s) and a PS
plan designed to address the question(s) or issue(s).
We have defined the following terms in Sec. 822.3 of this proposed
rule: Act, designated person, device failure, general plan guidance,
investigator, life-supporting or life-sustaining device used outside a
device user facility, manufacturer, postmarket surveillance,
[[Page 52379]]
prospective surveillance, serious adverse health consequences, specific
guidance, surveillance question, and unforeseen adverse event.
Proposed Sec. 822.4 states that the regulation applies to any
manufacturer that has been ordered to conduct PS by the agency, and
identifies the statutory criteria that must be met before we may order
PS.
C. Notification
Section 522(a) of the act provides criteria a device must meet
before we can impose PS. We may order PS of any class II or class III
device if: (1) The failure of the device would be reasonably likely to
have adverse health consequences, (2) the device is intended to be
implanted for more than 1 year, or (3) the device is intended to be
life-sustaining/life-supporting and is used outside a device user
facility. This provision applies to all such devices, including devices
that we review under the act, and devices (such as licensed in vitro
diagnostic products) that we review under the licensing provisions of
section 351 of the Public Health Service Act. In addition to the
statutory criteria, we have developed additional discretionary criteria
to determine when PS under section 522 of the act is an appropriate
mechanism for addressing a PS question or issue. We have discussed
these criteria in ``Guidance on Criteria and Approaches for Postmarket
Surveillance'' (www//fda.gov/cdrh/modact/critappr.pdf). Because we will
make determinations about PS on a case-by-case basis, we will notify a
manufacturer in writing of the requirement to conduct PS (proposed
Sec. 822.5) as soon as we make the determination (proposed Sec. 822.6).
This may be during the review of the marketing application for the
device, as the device goes to market, or after the device has been
marketed for some period of time. This notification is referred to as
the surveillance ``order'' and will specify the device(s) subject to
the surveillance order, the reason that we are requiring PS, and any
general or specific guidance that is available. We have identified the
mechanisms available to appeal our decision to order PS of a particular
medical device (proposed Sec. 822.7).
We recognize that a manufacturer may have difficulty designing and
submitting a PS plan to FDA within the statutory timeframe of 30 days
from receipt of a surveillance order. We may, therefore, request a
meeting with the affected manufacturer(s) to discuss the surveillance
question and the possible approaches for the surveillance. We
anticipate that this would generally occur prior to issuing a
surveillance order for a particular device for the first time, and
would be less likely to occur for subsequent orders for the same or
similar devices. We may also request information from or meetings with
manufacturers to determine whether a surveillance order is appropriate
and necessary.
D. Postmarket Surveillance Plan
By law, the manufacturer must submit a plan to conduct PS within 30
days of receipt of notification of the requirement to conduct PS (the
order). The manufacturer would be required to submit the original and
two copies of the plan (proposed Sec. 822.8). Under the proposed rule,
foreign manufacturers will be subject to the same reporting
requirements as domestic manufacturers. We believe that the inclusion
of foreign manufacturers will provide information that is needed to
ensure the safety of medical devices. Domestic manufacturers marketing
a device for export only are also subject to the provisions of section
522(a) of the act because they are introducing the device into
interstate commerce under the terms of the act.
We have identified the contents of the submission in proposed
Sec. 822.9, and the issues to be addressed in the design of the PS plan
in proposed Sec. 822.11. It is essential that the manufacturer design
the plan to address the specific PS question we have identified in the
order. We will include guidance to manufacturers regarding the content,
preparation, and submission of PS plans in the surveillance order.
The plan must clearly describe the content and timing of interim
and final reports. Each plan must outline reporting objectives, the
rationale for each objective, a description of information to be
reported, a description of reporting mechanisms, and proposed
timeframe(s) (proposed Sec. 822.10).
The statute requires that we determine that the person designated
to conduct the surveillance has appropriate qualifications and
experience. The qualifications and experience necessary will depend on
the surveillance approach being used. For example, a person qualified
to conduct a review and analysis of the literature and complaint files
would not necessarily be qualified to conduct a prospective clinical
study. Under proposed Sec. 822.9, the plan must clearly establish the
qualifications and experience of the designated person responsible for
conducting the proposed surveillance.
Proposed Sec. 822.12 identifies guidance documents available to
assist a manufacturer in the preparation of a submission or the design
of a PS plan. ``Guidance on Criteria and Approaches for Postmarket
Surveillance'' is also available through the Center for Devices and
Radiological Health (CDRH) Facts-on-Demand system and on the Internet
at the CDRH website at http://frwebgate.access.gpo.gov/cgi-bin/leaving.cgi?from=leavingFR.html&log=linklog&to=http://www.fda.gov/cdrh/modact/critappr.pdf.
Proposed Sec. 822.14 describes the procedure for incorporating by
reference information that the manufacturer has submitted in premarket
or other postmarket submissions. For example, a manufacturer may
reference the description of a device that he submitted as part of the
premarket notification (510(k)) submission, or the PS plan that he
submitted for another device. We believe referencing information will
reduce duplicative reporting, thereby reducing the burden on both the
manufacturer and FDA.
Proposed Sec. 822.15 discusses the PS period. The statute limits
the prospective surveillance period to 36 months, unless FDA and the
manufacturer agree to a longer period. The surveillance period is the
duration of actual surveillance, not the time elapsed since the
issuance of the surveillance order. If we determine that a longer
period of prospective surveillance is necessary and the manufacturer
does not agree, FDA and the manufacturer may employ dispute resolution
under section 562 of the act (21 U.S.C. 360bbb-1). We are in the
process of issuing a guidance on using dispute resolution to resolve
scientific disputes concerning the regulation of medical devices.
In general, the regulations governing protection of human subjects
(21 CFR part 50) and institutional review boards (IRB's) (21 CFR part
56) apply to studies of unapproved and approved products regulated by
FDA. This may include PS studies, depending on the approach used. There
are some approaches to PS, such as the review of published literature,
where the informed consent and IRB regulations would not be applicable.
For other types of studies, for example, prospective studies, the
patient should be provided with the basic elements of informed consent,
including the extent to which records would be kept confidential.
Therefore, a manufacturer should consider the need for IRB approval and
informed consent when designing a surveillance plan.
The above discussion regarding informed consent and IRB approval is
not intended to preempt any State or local requirement to obtain
informed consent or IRB approval. In addition, individual institutions
may have requirements for informed consent and
[[Page 52380]]
IRB approval that apply to all researchers.
FDA does not require, nor do we generally expect, PS to result in
the collection of personal identifiers. In any PS study, we expect
manufacturers to ensure that the surveillance approach they use
incorporates whatever measures are appropriate to protect patient
privacy. Some approaches to PS, such as the review of published
literature, would not require the manufacturer to take any specific
steps to protect patient privacy. Moreover, many existing data bases
and registries either do not capture individual identifying data or
restrict access to any information that would identify an individual
patient. It is unlikely, therefore, that personal identifiers will be
associated with study information.
In some cases, however, we may determine that a particular PS plan
requires the sponsor to take special measures to protect patient
privacy. A PS plan that includes collection of personal information in
identifiable form should include procedures that minimize any
likelihood that patient identifiers will be transferred from the health
care provider to the sponsor or any other third party except for
purposes of the surveillance activity, and then only under conditions
ensuring that it will be used for no other purpose.
We invite comments on the issue of informed consent for PS.
E. FDA Review and Action
In proposed Sec. 822.16, we describe the FDA review process for PS
submissions. We will first determine that the submission is
administratively complete, i.e., that the manufacturer has addressed
all of the elements in proposed Sec. 822.9. We will then evaluate
whether the surveillance plan is likely to result in the collection of
data that will answer the surveillance question. We will evaluate the
plan for scientific soundness, feasibility, and appropriateness to
address the surveillance question. We will then evaluate the
qualifications and experience of the person the manufacturer has
designated to conduct the surveillance.
Section 522(b) of the act requires that we review PS plan
submissions within 60 days of receipt (proposed Sec. 822.17). We will
notify the manufacturer in writing of the result of our review and
identify any actions the manufacturer must take (proposed Sec. 822.18).
Proposed Sec. 822.19 is a table that identifies the kinds of decisions
that we may make, based on the adequacy of the PS plan, and the action
that a manufacturer must take as a result of our decision. For example,
if we send a manufacturer a letter stating that specific revisions or
information must be submitted before we can approve the plan (an
``approvable'' letter), the manufacturer must address the concerns in
the letter and submit a revised plan within the specified timeframe. We
intend to use an interactive review process whenever feasible, so some
revisions may be requested, made, and submitted before a final decision
letter is issued.
Proposed Sec. 822.20 describes the consequences of failure to
submit a PS plan, failure to conduct surveillance in accordance with an
approved plan, or failure to submit a revised plan after we disapprove
a plan. Each of these failures is a failure to comply with section 522
of the act. As discussed in section I.B of this document, the failure
to comply with section 522 of the act is prohibited under section
301(q) of the act. This would also mean that the device is misbranded
under section 502(t)(3) of the act.
Any proposed modifications or changes in an ongoing study by the
manufacturer must be submitted in writing for FDA approval prior to
execution. For example, if there is a change in the designated person,
the manufacturer must submit information regarding the qualifications
and experience of the proposed replacement. Periods of PS under a
protocol with unapproved changes may invalidate the study. Final
authorization of any change rests with the agency (proposed
Sec. 822.21).
Proposed Sec. 822.22 discusses the procedures to be followed if FDA
and the manufacturer do not agree about the content of the plan or if
we disapprove the plan. We anticipate that most disagreements will be
resolved through a meeting with the Director of the Office of
Surveillance and Biometrics, CDRH. If there are still areas of
disagreement about the content of the plan, a manufacturer may use the
dispute resolution process (see discussion under proposed Sec. 822.15
above) or request a hearing under 21 CFR part 16.
Proposed Sec. 822.23 discusses the confidentiality of the plan.
Until the plan is approved, FDA considers the contents of the
submission confidential. Once we approve the plan, the contents of the
original submission, amendments, supplements, and reports are
disclosable in accordance with the Freedom of Information Act. We will
continue to protect the confidentiality of trade secret or commercial
confidential information, and information identifying individual
patients.
F. Responsibilities of Manufacturers
Manufacturers subject to this proposed rule must submit a plan to
conduct PS within 30 days of receipt of the surveillance order
(proposed Sec. 822.24). Once the plan has been approved, the
manufacturer must conduct the surveillance in accordance with the
approved plan (proposed Sec. 822.25). This means that the manufacturer
must ensure that he initiates PS in a timely manner, conducts the
surveillance in a scientifically sound manner, collects the data
identified in the plan, and submits required reports in a timely
manner. The surveillance plan and the approval order will identify
timeframes for initiation of the surveillance and submission of
reports.
Any change of ownership of the device results in a change of
responsibility for the corresponding surveillance plan, and does not
terminate it (proposed Sec. 822.26). This applies whether the company,
as a whole, changes ownership, or if only the rights to manufacture and
sell the device change hands. The proposed rule contains one exception
to this requirement. A manufacturer subject to this rule that is going
out of business, permanently and completely, must notify FDA and
discuss plans to complete or terminate PS and identify where and by
whom the records will be retained (proposed Sec. 822.27). This
exception would not apply if a manufacturer ceases distribution of a
device subject to PS but still continues to do any other business;
under those circumstances, the manufacturer must continue to fulfill
the PS requirements (proposed Sec. 822.28).
G. Waivers and Exemptions
We recognize that there may be some circumstances where a specific
requirement of this regulation may not apply or may not be feasible,
given the surveillance question and the design of the PS plan.
Therefore, we will consider a request for a waiver of any specific
requirement of this regulation. The manufacturer may submit this
request as part of the PS plan submission or separately but must
include information supporting the request (proposed Sec. 822.29).
We will consider a request for exemption from the requirement to
conduct PS for a manufacturer's device or a specific model of the
device. The request must explain why we should exempt the device or
specific model from PS and demonstrate why the surveillance question
does not apply (e.g., the device does not have the
[[Page 52381]]
characteristic or feature that has raised the surveillance question) or
does not need to be answered. Requests for exemption should not be used
to request reconsideration of our determination that PS is necessary to
address a public health or safety and effectiveness issue; a
manufacturer may not submit a request for a waiver or exemption in lieu
of the surveillance plan.
H. Records and Reports
Proposed Secs. 822.31 and 822.32 specify the records to be
maintained by the manufacturer and by the investigator. These records
include correspondence between FDA and the manufacturer, the
manufacturer and the investigator, and between investigators; signed
investigator agreements; the approved PS plan; documentation of the
date and reason for any deviation from the plan; all data collected and
analyses conducted for PS; and any other records required by regulation
or by order. The manufacturer must retain all records for a period of 2
years after we have accepted the final report. Under some
circumstances, we may require, by order, that the records be retained
for a longer period of time (proposed Sec. 822.33).
If there is a transfer of ownership or an investigator in the plan
changes, the manufacturer must ensure that all records are transferred
to the new manufacturer or investigator and that we are notified within
10 days of the effective date of the change. The notification must
include the name, address, and telephone number of the new manufacturer
or investigator and certify that all records have been transferred on
the specified date (proposed Sec. 822.34).
We will review manufacturers' PS programs during inspections. In
addition, persons with PS obligations other than manufacturers, e.g.,
clinical investigators, will be subject to periodic inspections. Any
person authorized to grant access must permit authorized FDA employees,
at reasonable times and in a reasonable manner, to enter and inspect
any facilities where devices are held (including any establishment
where devices are packed, held, used, or implanted, or where records of
results from the use of devices are kept) (proposed Sec. 822.35).
In general, we expect manufacturers to be able to produce records
required under the proposed rule within 72 hours of the initiation of
an inspection (proposed Sec. 822.36). This includes records and
information required to be kept by this regulation that are in the
possession of others under contract with the manufacturer to conduct
the manufacturer's PS. We will state the reason or purpose for the
request, and will identify to the fullest extent possible the
information or type of information we are seeking. Proposed Sec. 822.37
discusses our authority to inspect and copy records that identify
subjects. Proposed Sec. 822.38 establishes that the manufacturer must
submit interim and final reports in accordance with the approved PS
plan. It also specifies that we may, in accordance with section 519(a)
of the act, request information or reports that are not part of the
plan when we believe that it is necessary for the protection of the
public health and the implementation of the act. In any such request,
we will identify the information to be provided, the reason for the
request, and identify how we will use the information.
III. When Will the Regulation Be Effective?
We are proposing that any final rule that may issue based on this
proposed rule become effective 30 days after its date of publication in
the Federal Register.
IV. What Is the Environmental Impact of This Regulation?
We have determined under 21 CFR 25.30(h) that this action is of a
class of actions that does not individually or cumulatively have a
significant effect on the human environment. Therefore, neither an
environmental assessment nor an environmental impact statement is
required.
V. What Is the Economic Impact of This Regulation?
A. Introduction
We have examined the impact of the proposed rule under Executive
Order 12866, the Regulatory Flexibility Act (5 U.S.C. 601-612) (as
amended by subtitle D of the Small Business Regulatory Fairness Act of
1996 (Public Law 104-121)), and the Unfunded Mandates Reform Act of
1995 (UMRA) (Public Law 104-4). Executive Order 12866 directs us to
assess all costs and benefits of available regulatory alternatives, and
when regulation is necessary, to select regulatory approaches that
maximize net benefits (including potential economic, environmental,
public health and safety, and other advantages; distributive impacts;
and equity). The Regulatory Flexibility Act requires us to analyze
regulatory options that would minimize any significant impact of a rule
on small entities. Section 202(a) of the UMRA requires that agencies
prepare a written statement of anticipated costs and benefits before
proposing any rule that may result in an expenditure by State, local,
and tribal governments, in the aggregate, or by the private sector, of
$100 million in any one year (adjusted annually for inflation).
We believe that this proposed rule is consistent with the
regulatory philosophy and principles identified in the Executive Order.
The proposed rule is not a significant regulatory action as defined by
the Executive Order. Exercise of our PS authority could have a
significant impact on a substantial number of small entities. We have
included a preliminary regulatory flexibility analysis at the end of
this section for comment. Finally, we have determined that the proposed
rule is not a significant action as defined in the UMRA, and will not
have an effect on the economy that exceeds $100 million in any one
year.
B. Objectives of the Proposed Rule
The objective of the proposed rule is to enhance the public health
by reducing the incidence of medical device adverse experiences. The
primary problem is that we currently lack data that may reveal
unforeseen adverse events relevant to the safety and effectiveness of
specific devices. The proposed rule will address this concern by
implementing section 522 of the act, as amended by FDAMA, to require
manufacturers of specific medical devices to conduct PS. We expect PS
to identify uncommon, but potentially life-threatening, device-related
outcomes that were not noted during premarket development, or were
noted as a continuing concern but did not warrant withholding the
device from the market.
C. Risk Assessment/Baseline Conditions
In the absence of the proposed regulations, neither FDA nor device
manufacturers will have complete confidence that uncommon and
unforeseen events have been adequately identified for marketed devices.
Currently, hundreds of medical devices are marketed each year for which
failure could be reasonably likely to have serious adverse health
consequences, or that are intended to be implanted in a human body for
more than 1 year, or that are life-sustaining or life-supporting and
used outside a device user facility. Devices with these characteristics
range from implantable pacemaker pulse generators and vascular graft
prostheses to dental and orthopedic implants.
Our decision to approve or clear a particular device for marketing
is based on a comparison of the expected health benefits of the device
to the expected risk of adverse outcomes due to device
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failure. Premarket clinical studies, however, are typically designed to
detect only relatively frequent adverse events. As a result, we often
base premarket approval decisions on risk/benefit relationships that
include only relatively frequent risks. Given this lack of complete
data, neither FDA nor device manufacturers can be confident about the
likelihood of serious, but infrequent, adverse events. Such events can
have drastic consequences on dozens, if not hundreds of patients when a
device is marketed to thousands of patients. PS provides a mechanism
for gaining an early awareness and better understanding of such rare
events, thus preventing further unnecessary risk to patients.
Surveillance may identify actions that minimize risks, such as
training, labeling, design modification, or patient selection criteria.
In extreme cases, surveillance may show that the subject device should
be removed from the market.
D. Costs of Postmarket Surveillance
A critical cost factor is the size of the expected surveillance. We
have approved some surveillance protocols under SMDA, but rescinded
most of these upon passage of FDAMA. While we cannot be precise, we
estimate, based on a review of currently marketed devices, that an
average of six generic device types, each with an average of five
manufacturers, may be the subject of PS orders each year. This
frequency would result in the initiation of 30 PS orders each year.
Assuming that the duration of each PS is limited to 3 years, at any
given time, 90 PS studies could be ongoing and subject to FDA review.
An additional 30 PS plans would be in preliminary, design stages.
The surveillance becomes larger and more extensive as the
acceptable rate of adverse events becomes smaller. Statisticians
explain that if one assumes a cumulative Poisson distribution, a 0.95
probability of noting an adverse event with the incidence rate of (p)
implies that the product of p and the number of observations (n) must
approximately equal 3 (i.e., pn=3). For example, the surveillance must
include about 30,000 observations to be 95 percent confident that a PS
will detect events that occur at a frequency of 0.0001 (1 event out of
10,000 observations). The PS designed to detect more frequent events
requires fewer observations. The surveillance must include about 1,500
observations to be 95 percent confident that PS will detect events that
occur at a frequency of 0.002 (2 events out of 1,000 observations). We,
along with device manufacturers, will need to take these considerations
into account when designing PS plans.
The manufacturer would generally complete the required PS within 36
months, with at least semiannual observations. (PS utilizing literature
searches may require monthly searches, although less frequent reviews
may be appropriate at times.) These observations would be collected by
either primary data collection from controlled clinical studies,
secondary data collected from other data bases or sources (such as
Medicare data bases, registries or tracking systems, and other types of
studies), or published studies in the medical literature as
supplemented by our current reporting systems. For purposes of this
analysis, we estimate that 10 percent of the PS will require primary
data collection, 50 percent may utilize secondary data sources, and 40
percent may collect adequate data from published reports. Manufacturers
will incur varying costs for both design and analysis/reporting/
recordkeeping phases of each surveillance in addition to the costs of
data collection. In addition, we will incur costs to review the data
submitted by manufacturers.
E. Design Costs
We would expect the manufacturer of each device that is subject to
a PS order to develop an analysis plan for implementing the data
collection. We would review and approve this plan prior to initiation.
The design of a PS utilizing primary data collection would require more
resources than either secondary collection or literature searches.
Senior industry regulatory staff would review and approve each type of
PS, however, before submission to us. For this estimate, we have
assumed that the design of PS utilizing primary data collection would
require 3 weeks of industry staff time, PS utilizing secondary data
sources would require 2 weeks of time, and PS utilizing published
literature would require only 1 staff week. According to the U.S.
Bureau of Labor Statistics (1997), in 1997 the median weekly rate of
compensation for managerial and professional personnel in this industry
group (SIC 3841) was approximately $1,300. We have assumed an
additional cost of $700 per week to account for administrative and
clerical resources for a total estimate of industry resources at $2,000
per week. Therefore, the design of PS utilizing primary data collection
would equal $6,000, PS utilizing secondary data collection would equal
$4,000, and PS utilizing only a literature search would equal $2,000.
These costs would occur prior to the first year of surveillance for
each study.
F. Costs of Data Collection
1. Costs for Primary Data Collection
Primary data collection utilizing clinical trials will generally be
impractical because of difficulties obtaining patient and clinician
participation. In addition, this type of data collection would have
significant resource requirements. Primary data could, however, be used
to survey smaller populations, or populations that could experience
relatively high rates of adverse events. For this analysis, we have
assumed that a rigorous PS plan might call for observing 300 subjects
semiannually over a 3-year period. This plan would generate 1,800 total
observations and might be confidently expected to identify adverse
events that occur with a frequency of 0.002, or 2 per 1,000. Moreover,
patient dropouts would occur and some observations would not result in
usable data, raising the number of required subjects to perhaps 350.
Physicians would examine patients and provide the results of these
required observations directly to manufacturers.
The costs of this data collection would be significant. While in
most cases, we would not require additional procedures or tests for a
patient, it is possible that some extra examinations would be required
to ensure that the patient's device was still functional. In addition,
normal physiologic data would likely be consistently recorded,
submitted to the device manufacturers, and archived for further review.
We have estimated that these data would require a direct cost of $150
per observation for the physician or medical facility to collect the
data and submit it in proper form to the sponsoring manufacturer.
Therefore, the cost of collecting these data would equal $300 per
patient per year, or $105,000 per year. The present value of the costs
of collecting these primary data over a 3-year period (using a 7
percent discount rate) is $276,000 per PS.
In addition, the patient/subject is likely to incur opportunity
costs associated with being part of PS clinical studies. Because the
ultimate purpose of the PS is to continue marketing the device, the
patient is likely to incur costs for procedures and tests that provide
him or her no direct benefit. We have estimated that such trials may
require approximately 1 hour of patient time (including travel).
Assuming that the opportunity cost of patients is approximately $26 per
hour, the annual cost to patients of lost opportunity for PS utilizing
primary data is $18,200 per year. The present value of the costs of
[[Page 52383]]
3 years of data collection (at 7 percent discount rate) is $48,000.
We, therefore, estimate the total present value of the costs for
primary data collection to be $324,000 per PS study.
2. Costs for Secondary Data Collection
The use of secondary data for PS would not be as costly as the use
of primary data. Manufacturers may obtain secondary data sets from both
public and private sources, depending on the nature of the proposed
surveillance, and we estimate that these data would cost approximately
$50,000 per year to obtain and maintain for each surveillance. These
data would include sufficient observations to ensure that infrequent
events would be identified, but the expected frequency level may vary
by device and patient characteristics. The present value of the costs
of using secondary data sources for PS (at a 7 percent discount rate
for 3 years) is $131,000.
3. Costs of Conducting Literature Searches
We believe that PS utilizing reviews of published literature and
analyses of our current reporting system may require monthly
collections, although less frequent reviews may be acceptable for some
surveillances. As a rule, we assume that a professional employee would
take approximately 3 days per month to assess published accounts and
ensure that any useful data are considered. As stated earlier, the
median weekly compensation rate for professional employees in this
industry was approximately $1,300 in 1997. This implies that the cost
of reviewing published literature would equal $780 per month for
professional staff resources. Administrative and clerical support would
likely add an additional $420 per month for a total cost of $1,200.
Annual costs for conducting this type of PS would equal $14,400, and at
a 7 percent discount rate, the present value of the costs of this data
collection equals $38,000.
G. Costs of Data Analysis, Reporting, and Recordkeeping
PS is likely to entail the preparation and submission of four
reports during the course of all types of surveillance: An initial
report at the outset, two annual interim reports, and a final report
including data analysis. In addition, manufacturers will be required to
keep data available for 2 years. We assume that this category of costs
is likely to be equivalent for each type of PS.
The initial and interim progress reports are expected to be
relatively brief. We expect that each report would require only 1
resource week of supported professional time to be completed for a cost
of $2,000 per report. The final data analysis and report would be much
more extensive, and could require up to 3 months of resources to
complete (statistical, medical research, legal, and senior regulatory
affairs staff would likely all have input to final reports). The
estimated cost of preparing and submitting a final PS report is
$26,000.
We estimate that the total cost of maintaining records for 2 years
after completion of the surveillance will equal $500 per year. The
present value of these reporting/recordkeeping costs (at a 7 percent
discount rate) equals $28,000 per surveillance.
H. Total Industry Costs of Postmarket Surveillance
The annual cost to industry for the conduct of PS is the sum of the
present value of the costs of the expected studies. Each PS requiring
primary data collection has a present value cost of $358,000 ($6,000
for design, $324,000 for data collection (including $48,000 of patient
opportunity cost), and $28,000 for reports and recordkeeping). Each PS
requiring secondary data collection has a present value cost of
$163,000 ($4,000 for design, $131,000 for data collection, and $28,000
for reports and recordkeeping). Each PS requiring literature searches
has a present value cost of $68,000 ($2,000 for design, $38,000 for
data collection, and $28,000 for reports and recordkeeping).
We expect to issue 30 PS orders each year. We expect that 10
percent (3 PS') of these will require primary data collection. The
present value of the costs for these surveillances is $1.1 million. We
expect that 50 percent (15 PS') of the 30 PS orders will use secondary
data collection. The present value of the costs for these surveillances
is $2.4 million. The remaining 40 percent of annual PS orders (12 PS')
will use literature searches. The present value of the costs for these
surveillances is $0.8 million. Since we expect to issue only 30
surveillance orders each year, the annual cost to industry of this
regulation is the sum of the present value costs, or $4.3 million.
I. Costs to FDA for Oversight and Review
We expect that 120 reports will be submitted each year as a result
of this regulation (30 initial reports, 60 interim progress reports,
and 30 final data analyses). If each report, on average, required 2
weeks of review time, we will need five review fulltime employees
(FTE's) to oversee the program. We would require an additional 2.5
FTE's in support and management resources. We have estimated that the
cost of each FTE is approximately $117,300. Therefore, the annual cost
to FDA of maintaining PS is estimated to equal $0.9 million per year.
J. Total Annual Costs of Postmarket Surveillance
We estimate that the total annual cost for operating and
maintaining a PS program is $5.2 million. Most of these costs ($4.3
million) are direct costs to manufactures while $0.9 million are our
costs of operating the program.
K. Benefits of the Proposed Rule
The expected benefit of the proposed rule is the reduction in
avoidable adverse events attributable to the earlier detection of
potential problems. Possible outcomes of PS include withdrawal of the
device from the market, changes in labeling, changes in user training,
modification of the device design, or (most likely) assurance that the
device does not pose an unreasonable risk to the public health. These
benefits are not easily quantified because they would vary by device;
but the greatest benefit would be realized when other regulatory
safeguards, such as early warning through the MDR system or
preproduction design controls, fail to detect and resolve serious
problems. To illustrate the potential benefits of PS, we reviewed our
historical records to identify and quantify the benefits of a major
adverse event that could reasonably have been mitigated if this
proposed rule had been in place.
L. Chronology of Historical Event
A particular type of implanted heart valve was approved and quickly
accepted for patient use in 1979 because of its ability to reduce the
risk of blood clots in patients. The premarket decision to approve the
device considered clinical data that included an observation of one
failure. The device was marketed for 8 years and implanted a total of
82,000 times. By 1999, there were 462 device failures and 300 resultant
fatalities.
During the first marketing year, 5,000 patients received the device
and 2 devices failed. During the second year, an additional 11,000
devices were implanted and 3 devices failed. During the third year,
14,000 devices were implanted and 7 devices failed. At this point of
marketing, a total of 30,000 devices had been implanted and 12 had
failed. No failures were reported in
[[Page 52384]]
other similar devices marketed during this period.
We believe that had PS been in effect at that time, we would have
likely made this device subject to a PS order because of the noted
premarket strut failure. In general, any failure to any heart valve
would have been deemed serious, and potentially catastrophic. We would
have been concerned about the occurrence of a strut failure during
premarket testing. While this concern would not have delayed marketing
approval, subsequent strut failures would have been sufficient to start
the PS mechanism, if it had been available.
A likely surveillance plan would have required the manufacturer to
determine the frequency of strut failures and identify contributing
causes. Such a plan would have likely detected problems with the device
by the end of the third year; potentially avoiding a total of 52,000
implants (82,000-30,000). Given the substantial number of patients
implanted and the relatively low failure rate for the number of
semiannual patient observations after 3 years (12<divide>102,000 =
.0001), it is unlikely that the required PS would have involved the
collection of primary data through prospective trials. Nevertheless, by
analyzing their respective failure rates by using patient registries
that would include all implanted devices, the manufacturer would have
noted all complications and failures. Special attention would have been
paid to all adverse events (both expected and unexpected), with special
attention paid to strut fractures, early valve replacement, and deaths.
Because all patients and all implants would have been entered into this
registry, each occurrence of valve fracture would have been noted, and
this information would have been used to determine the best course of
action to protect the public health. In this case, it is likely that no
valves would have been implanted in patients after the third year of
marketing.
M. Postmarket Surveillance and Risk Reduction
If PS prevented 63 percent of the actual implants
(52,000<divide>82,000), then it is likely that about 63 percent of the
device failures could also have been avoided. As of 1999, the device
has failed 462 times. Consequently, if the device had been removed from
the market after its third year, about 293 failures would have been
avoided over an 18-year period (1981 to 1999). Moreover, the 65 percent
fatality rate for failures implies that the 190 fatalities associated
with these 293 failures would have been avoided.
N. Value of Avoided Mortality
There are no precise methodologies for estimating the value of
preventing human fatalities. Economists, however, have attempted to
place a dollar value on the avoidance of fatal risks based on society's
implicit willingness to pay to avoid such risks. Currently, the
literature shows that $5 million may represent an approximate value of
society's willingness to pay to avoid a statistical fatality. This
value is reduced by an appropriate discount factor, however, to the
extent that the averted fatalities would occur in future time periods.
O. Frequency of Adverse Events
To develop a possible scenario of future benefits we have assumed
that, once within the next 25 years, the rule would prevent an event
with characteristics identical to the heart valve incident discussed
above. We cannot predict the precise year of the expected future event,
but based on the past pattern of device failures, if the proposed rule
identified a device with the described failure characteristics in the
first year after completion of the first surveillance group (actually
the fourth year of implementation), the current present value dollar
benefit (assuming a 7 percent interest rate) of the avoided fatalities
would be $405.5 million. If PS identified a potential device failure
during the 10th project year, the present value of the dollar benefits
for that event would be $270.2 million. If the device failure were not
identified until the 25th year, the present value of the monetized
benefits would be $97.9 million. Because we assume that, in the absence
of this rule, the device failure would occur only once during the next
25 years, the likelihood of an initial failure in any 1 future year is
only .04. Thus, we estimate the overall expected present value of
avoiding such a future device failure at $192.0 million.
However, PS is not expected to be infallible. We have estimated
that typical PS design will provide a 95 percent confidence that
infrequent adverse events will be identified. Therefore, we would
expect to identify potential device failures such as described 95
percent of the time. To account for this, the present value of avoiding
future device failures attributable to this proposed regulation is
expected to equal 95 percent of the total amount, or $182.4 million.
P. Annual Benefits of the Proposed Rule
In the illustrative case described above, we have amortized
society's willingness to pay to avoid these fatalities over the
evaluation period. This is because the costs of PS are ongoing and
would be expended each year whether a device failure occurred or not.
The current net value of avoiding these fatalities ($182.4 million),
when amortized over 25 years, using a 7 percent discount rate, will
result in average annualized benefits of $15.7 million.
Q. Annual Costs and Benefits of the Proposed Rule
We have estimated the annual costs of PS to equal $5.2 million. We
estimated benefits based on the avoidance over the next 25 years of
just one serious event to equal $15.7 million per year.
R. Small Business Analysis/Initial Regulatory Flexibility Analysis
We believe that it is likely that the proposed rule will have a
significant impact on a substantial number of small entities and have
conducted an initial regulatory flexibility analysis. This analysis is
intended to assess the impact of the rule on small entities and to
alert any potentially impacted entities of the expected impact. We
request that such entities review the proposed rule and submit comments
to us.
S. Description of Impact
The objective of the proposed rule is to reduce the number of
adverse events associated with failure of medical devices by
implementing section 522 of the act, as amended by FDAMA, to require PS
of specific devices. This surveillance will be designed to identify, as
early as possible, potentially dangerous but rare adverse device-
related events. Our statutory authority for the proposed rule is
discussed earlier in this preamble.
Makers of four categories of devices are likely to be affected by
the proposed regulations: Diagnostic substances (SIC 2835), surgical
and medical instruments (SIC 3841), dental equipment and supplies (SIC
3843), and ophthalmic goods (SIC 3851). This proposed rule would affect
manufacturers (regardless of size) of: (1) Devices for which failure
would be reasonably likely to have severe health consequences, (2)
devices to be implanted in a human body for more than 1 year, and (3)
devices that are life-sustaining or life-supporting outside a device
user facility, because PS will likely be required for some of their
currently marketed and new devices.
Manufacturers within these industry groups are typically small.
Over 65 percent of the establishments in these 4 industries have 20 or
fewer employees and the companies have an average of
[[Page 52385]]
1.09 establishments per company. Manufacturers in these industries are
highly specialized, with between 83 and 98 percent of establishment
sales within the affected industries. In addition, between 84 and 98
percent of diagnostic, medical, dental, and ophthalmic products are
supplied by establishments within these industries. The Small Business
Administration classifies as small any entity with 500 or fewer
employees for all 4 industries. There is a high likelihood that
manufacturers of some of the devices that would be subject to this
proposed rule will include small entities.
The average company in these industries has about $9.8 million in
annual revenues and about 72 employees. Based on the cost assumptions
described above, any company conducting PS with primary data collection
would expend 3.7 percent of annual revenues. Secondary data collection
would cost an average company 1.7 percent of annual revenues.
(Literature searches are not expected to impose significant costs).
Because 60 percent of the expected PS orders would require significant
outlays, we believe that a substantial number of small entities would
be significantly affected.
We specifically solicit comment on the issue of the impact of this
proposed rule on small entities.
T. Analysis of Alternatives
We examined and rejected the following alternatives to the proposed
rule: (1) No action, (2) reliance on premarket approval application
(PMA) annual reports, (3) increased use of PMA postapproval studies,
(4) reliance on MDR reports, (5) increased educational effort to
improve all reporting mechanisms, and (6) exemption of small
manufacturers from PS requirements. We have rejected these alternatives
at this time for the following reasons:
Alternative 1
Other sources of postmarket data or information exist, including
PMA annual reports and other mechanisms. However, these sources are not
always adequate to address specific postmarket issues that arise for
specific devices. The proposed rule describes a process that is
intended to identify sources of information available to the agency and
determine their ability to address the postmarket issue prior to
issuing a PS order. We would be able to meet with the affected industry
sector to determine what information is currently available and whether
that information may be modified to answer specific public health
questions. Reliance on the current sources of postmarket data would not
efficiently meet the objective of reducing avoidable adverse events.
Alternative 2
We considered increasing the requirements for data submission in
PMA annual reports. This alternative was rejected because not all
devices that meet the PS criteria are subject to PMA annual reports,
and annual reports would not be specific enough to address issues for
each type of device. In addition, the costs of requiring detailed data
submissions for all affected devices would be extremely high. We
rejected this alternative.
Alternative 3
If we increased postapproval studies, the expected compliance costs
would be much greater, since postapproval studies generally consist of
primary data collection. If a postmarket issue is identifiable at the
time of approval, postapproval studies could be designed to collect
meaningful data. However, if an issue would arise after FDA approval,
this mechanism would not be helpful in meeting the objectives of the
proposed rule. In addition, because all class II devices are marketed
through premarket notification procedures, postapproval studies are not
an option. We rejected this alternative.
Alternative 4
We rejected the alternative of relying on an enhanced MDR system.
While MDR's are extremely important in assessing public health, it is a
passive system of data collection that relies on reports from concerned
professionals and manufacturers or their representatives who become
aware of device problems. Often MDR reports are not specific enough to
address discrete issues. We believe that the public health objectives
are better met by requiring more active data collection and analysis by
the responsible manufacturers of particular devices.
Alternative 5
FDA did not select the alternative of increased education in lieu
of PS because any educational effort would require that FDA have
sufficient information. Surveillance would be ordered to collect
information that might lead to educational efforts to correct any noted
problem. Thus, FDA did not believe that education alone would reduce
adverse events.
Alternative 6
We rejected the alternative of exempting small device manufacturers
from the proposed requirements. We recognize that surveillance would
likely cause a significant impact on small entities. However, the vast
majority of device manufacturers are small and any exemption would
seriously reduce the effectiveness of the proposed rule. In addition,
devices manufactured by small entities could as easily meet the
criteria the law establishes and FDA uses to impose a PS order.
We solicit comments on any other alternatives that meet the stated
objective.
U. Ensuring Small Entity Participation in Rulemaking
We believe it is possible that the proposed rule could have a
significant impact on a substantial number of small entities. The
impact would include the costs of conducting PS for specific devices.
We solicit comments from affected entities to ensure this impact is
analyzed.
The proposed rule will be available on the Internet at http://frwebgate.access.gpo.gov/cgi-bin/leaving.cgi?from=leavingFR.html&log=linklog&to=http://www.fda.gov for review by all interested parties and comments
considered. In addition, CDRH's Division of Small Manufacturers
Assistance will distribute the proposed rule through its established
procedures for information dissemination during the comment period to
ensure there is wide notice of the proposed rule and to solicit
comments from small businesses.
VI. Conclusions
We have examined the impacts of the proposed rule implementing PS
for specific medical devices. Based on these estimates, the average
annual quantified benefits of $15.7 million exceed the average
annualized costs of conducting surveillance ($5.2 million). These
benefits assume that between three and four statistical fatalities will
be avoided each year because of this proposed rule. We also expect
additional benefits, not easily quantifiable, such as assurance that a
marketed device does not pose an unreasonable risk to the public health
and improvements in the design, labeling, and user training for
devices.
We have concluded that it is likely that this rule will have a
significant economic impact on a substantial number of small entities.
We solicit comment on all aspects of this analysis and all
assumptions used.
VII. How Can I Comment on This Proposed Rule?
A. Electronic Access and Filing Address
You may view an electronic version of this proposed rule on the
Internet at http://frwebgate.access.gpo.gov/cgi-bin/leaving.cgi?from=leavingFR.html&log=linklog&to=http://www.fda.gov. You may also
[[Page 52386]]
comment on the Internet at: http://frwebgate.access.gpo.gov/cgi-bin/leaving.cgi?from=leavingFR.html&log=linklog&to=http://www.accessdata.fda.gov/scripts/oc/dockets/comments/commentdocket.cfm. Please include ``Attention: Docket
No. 00N-1367'' and your name and return address in your Internet
message. If you do not receive a confirmation from the system that we
have received your Internet message, contact us directly at 301-827-
6880. FDA is working to set up a system that would allow commenters to
view already submitted comments. When this system is available, we will
publish a notice in the Federal Register.
B. Written Comments
You may send written comments on this proposed rule electronically
or by hard copy (see the ADDRESSES section).
All comments on the proposed rule should be specific, confined to
issues pertinent to the proposed rule, and should explain the reason
for any recommended change. Where possible, you should reference the
specific section or paragraph of the proposal that you are addressing.
FDA may not consider or include in the administrative record for the
final rule comments that we receive after the close of the comment
period (see the DATES section) or comments delivered to an address
other than that listed above (see the ADDRESSES section).
VIII. How Does This Regulation Comply With the Paperwork Reduction
Act of 1995?
This proposed rule contains information collection provisions that
are subject to review by the Office of Management and Budget (OMB)
under the Paperwork Reduction Act of 1995 (the PRA) (44 U.S.C. 3501-
3520). A description of these provisions is given below with an
estimate of the annual reporting and recordkeeping burden. The estimate
includes the time for reviewing instructions, searching existing data
sources, gathering and maintaining the data needed, and completing and
reviewing each collection of information.
With respect to the following collection of information, FDA
invites comments on: (1) Whether the proposed collection of information
is necessary for the proper performance of FDA's functions, including
whether the information will have practical utility; (2) the accuracy
of FDA's estimate of the burden of the proposed collection of
information, including the validity of the methodology and assumptions
used; (3) ways to enhance the quality, utility, and clarity of the
information to be collected; and (4) ways to minimize the burden of the
collection of information on respondents, including through the use of
automated collection techniques, when appropriate, and other forms of
information technology.
Title: Postmarket Surveillance
Description: FDA is proposing to implement the PS provisions of
section 522(a) of the act, as added to the act by the SMDA and amended
by FDAMA. The purpose of these proposed changes is to provide for the
collection of useful data and other information necessary to protect
the public health and to provide safety and effectiveness information
about the device after the device is marketed. This data or information
would be different from and supplemental to information collected under
other provisions, such as MDR.
Description of Respondents: Manufacturers.
FDA estimates the burden for this collection of information as
follows:
Table 1.--Estimated Annual Reporting Burden<SUP>1</SUP>
----------------------------------------------------------------------------------------------------------------
Annual
21 CFR Section No. of Frequency per Total Annual Hours per Total Hours
Respondents Response Responses Response
----------------------------------------------------------------------------------------------------------------
822.9 and 822.10 30 1 30 120 3,600
822.21 7 1 7 40 280
822.27 1 1 1 8 8
822.28 3 1 3 40 120
822.29 5 1 5 40 200
822.30 1 1 1 120 120
822.34 5 1 5 20 100
822.38 90 2 180 80 14,400
Total 18,828
----------------------------------------------------------------------------------------------------------------
\1\There are no capital costs or operating and maintenance costs associated with this collection of information.
Table 2.--Estimated Annual Recordkeeping Burden<SUP>1</SUP>
----------------------------------------------------------------------------------------------------------------
Annual
21 CFR Section No. of Frequency per Total Annual Hours per Total Hours
Recordkeepers Recordkeeping Records Recordkeeper
----------------------------------------------------------------------------------------------------------------
822.31 90 1 90 20 1,800
822.32 270 1 270 10 2,700
Total 4,500
----------------------------------------------------------------------------------------------------------------
\1\There are no capital costs or operating and maintenance costs associated with this collection of information.
FDA has had limited experience with PS under SMDA, and FDAMA
significantly modified the provisions of section 522 of the act. We
expect that at least some of the manufacturers will be able to satisfy
the PS requirement using information or data they already have or are
already collecting for other purposes. For purposes of calculating
burden, however, we have assumed that each PS order can only be
satisfied by a 3-year clinically-based surveillance plan, using three
investigators. Based on current staffing and resources, we anticipate
that we will identify surveillance issues for 6 generic devices each
year. On average, 5 different manufacturers will market each of those
devices, so we expect to issue 30 PS orders each year.
Each manufacturer will be required to submit a PS plan (21 CFR
822.8 and 822.10) within 30 days of the receipt of the order and
interim and final reports on the progress of the surveillance (21 CFR
822.38) during the course of the surveillance. After the third year of
[[Page 52387]]
implementation, 30 manufacturers will complete their surveillance each
year. Therefore, by year three, we will have reached a steady state,
with 90 manufacturers and 270 investigators in various stages of PS
each year. We anticipate that we may occasionally ask for additional
information, such as distribution numbers or patterns, on a case-by-
case basis. We anticipate that a small number of respondents will
propose changes to their PS plans (21 CFR 822.21), request a waiver of
a specific requirement of this regulation (21 CFR 822.29), or request
exemption from the requirement to conduct PS of their device (21 CFR
822.30). Our experience has shown that a few respondents will go out of
business (21 CFR 822.27) or cease marketing the device subject to PS
(21 CFR 822.28) each year. In addition, manufacturers must certify
transfer of records if the sponsor or the investigator in the plan
changes (21 CFR 822.34). We anticipate that this will apply to a small
number of respondents.
The regulations in 21 CFR 822.26 do not constitute information
collection subject to review under the PRA because ``it entails no
burden other than that necessary to identify the respondent, the date,
the respondent's address, and the nature of the instrument'' (21 CFR
1320.3(h)(1)).
In compliance with section 3507(d) of the PRA, we have submitted
the information collection requirements of this proposed rule to OMB
for review. Interested persons are requested to send comments regarding
information collection by September 28, 2000, 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.
List of Subjects in 21 CFR Part 822
Postmarket surveillance, Medical devices, Reporting and
recordkeeping requirements.
Therefore, under the Federal Food, Drug, and Cosmetic Act and under
authority delegated to the Commissioner of Food and Drugs, it is
proposed that 21 CFR part 822 be added to read as follows:
PART 822--POSTMARKET SURVEILLANCE
Subpart A--General Provisions
Sec.
822.1 What does this part cover?
822.2 What is the purpose of this part?
822.3 How do you define the terms used in this part?
822.4 Does this part apply to me?
Subpart B--Notification
822.5 How will I know if I must conduct postmarket surveillance?
822.6 When will you notify me that I am required to conduct
postmarket surveillance?
822.7 What should I do if I do not agree that postmarket
surveillance is appropriate?
Subpart C--Postmarketing Surveillance Plan
822.8 When, where, and how must I submit my postmarket surveillance
plan?
822.9 What must I include in my submission?
822.10 What must I include in my surveillance plan?
822.11 What should I consider when designing my plan to conduct
postmarket surveillance?
822.12 Do you have any information that will help me prepare my
submission or design my postmarket surveillance plan?
822.13 [Reserved]
822.14 May I reference information previously submitted instead of
submitting it again?
822.15 How long must I conduct postmarket surveillance of my
device?
Subpart D--FDA Review and Action
822.16 What will you consider in the review of my submission?
822.17 How long will your review of my submission take?
822.18 How will I be notified of FDA's decision?
822.19 What kinds of decisions may FDA make?
822.20 What are the consequences if I fail to submit a postmarket
surveillance plan, my plan is disapproved and I fail to submit a new
plan, or I fail to conduct surveillance in accordance with my
approved plan?
822.21 What must I do if I want to make changes to my postmarket
surveillance plan after you have approved it?
822.22 What recourse do I have if I do not agree with your
decision?
822.23 Is the information in my submission considered confidential?
Subpart E--Responsibilities of Manufacturers
822.24 What are my responsibilities once I am notified that I am
required to conduct postmarket surveillance?
822.25 What are my responsibilities after my postmarket
surveillance plan has been approved?
822.26 If my company changes ownership, what must I do?
822.27 If I go out of business, what must I do?
822.28 If I stop marketing the device subject to postmarket
surveillance, what must I do?
Subpart F--Waivers and Exemptions
822.29 May I request a waiver of a specific requirement of this
part?
822.30 May I request exemption from the requirement to conduct
postmarket surveillance?
Subpart G--Records and Reports
822.31 What records am I required to keep?
822.32 What records are the investigators in my surveillance plan
required to keep?
822.33 How long must we keep the records?
822.34 What must I do with the records if the sponsor of the plan
or an investigator changes?
822.35 Can FDA inspect my manufacturing site or other sites
involved in my postmarketing surveillance plan?
822.36 Can FDA inspect and copy the records related to my
postmarket surveillance plan?
822.37 Under what circumstances would FDA inspect records
identifying subjects?
822.38 What reports must I submit to FDA?
Authority: 21 U.S.C. 331, 352, 360l, 330l, 371.
Subpart A--General Provisions
Sec. 822.1 What does this part cover?
This part implements section 522 of the Federal Food, Drug, and
Cosmetic Act (the act) by providing procedures and requirements for
postmarket surveillance of certain types of devices. If you fail to
comply with requirements FDA orders under section 522 of the act and
this part, your device is considered misbranded under section 502(t)(2)
of the act and you are in violation of section 301(q)(1)(C) of the act.
Sec. 822.2 What is the purpose of this part?
This purpose of this part is to implement our postmarket
surveillance authority to maximize the likelihood that these postmarket
plans will result in the collection of useful data. These data can
reveal unforeseen adverse events, the actual rate of anticipated
adverse events, and other information necessary to protect the public
health.
Sec. 822.3 How do you define the terms used in this part?
Some of the terms we use in this part are specific to postmarket
surveillance and reflect the language used in the statute (law). Other
terms are more general and reflect FDA's interpretation of the law.
This section of the part defines the following terms:
(a) Act means the Federal Food, Drug, and Cosmetic Act (21 U.S.C.
301 et seq.), as amended.
(b) Designated person means the individual who conducts or
supervises the conduct of your postmarket surveillance. If your
postmarket surveillance plan includes a team of investigators, as
defined below, the designated person is the responsible leader of that
team.
[[Page 52388]]
(c) Device failure means a device does not perform or function as
intended, and includes any deviation from the device's performance
specifications or intended use.
(d) General plan guidance means agency guidance that provides
information about the requirement to conduct postmarket surveillance,
the submission of a plan to the agency for approval, the content of the
submission, and the conduct and reporting requirements of the
surveillance.
(e) Investigator means an individual who collects data or
information in support of a postmarket surveillance plan.
(f) Life-supporting or life-sustaining device used outside a device
user facility means that a device is essential to, or yields
information essential to, the restoration or continuation of a bodily
function important to the continuation of human life and is used
outside a hospital, nursing home, ambulatory surgical facility, or
diagnostic or outpatient treatment facility. A physician's office is
not a device user facility.
(g) Manufacturer means any person, including any importer,
repacker, and/or relabeler, who manufactures, prepares, propagates,
compounds, assembles, processes, or engages in any of the activities
described in Sec. 807.3(d) of this chapter.
(h) Postmarket surveillance means the active, systematic,
scientifically valid collection, analysis, and interpretation of data
or other information about a marketed device.
(i) Prospective surveillance means that the subjects are identified
at the beginning of the surveillance and data or other information will
be collected from that time forward (as opposed to retrospective
surveillance).
(j) Serious adverse health consequences means any significant
adverse experience related to a device, including device-related events
that are life-threatening or that involve permanent or long-term
injuries or illnesses.
(k) Specific guidance means guidance that provides information
regarding postmarket surveillance for specific types or categories of
devices or specific postmarket surveillance issues. This type of
guidance may be used to supplement general guidance and may address
such topics as the type of surveillance approach that is appropriate
for the device and the postmarket surveillance question, sample size,
or specific reporting requirements.
(l) Surveillance question means the issue or issues to be addressed
by the postmarket surveillance.
(m) Unforeseen adverse event means any serious adverse health
consequence that is either not addressed in the labeling of the device
or occurs at a rate higher than anticipated.
Sec. 822.4 Does this part apply to me?
If we have ordered you to conduct postmarket surveillance of a
medical device under section 522 of the act, this part applies to you.
We have the authority to order postmarket surveillance of any class II
or class III medical device, including a device reviewed under the
licensing provisions of section 351 of the Public Health Service Act,
that meets any of the following criteria:
(a) Failure of the device would be reasonably likely to have
serious adverse health consequences;
(b) The device is implanted in the human body for more than 1 year;
or
(c) The device is used to support or sustain life and is used
outside a user facility.
Subpart B--Notification
Sec. 822.5 How will I know if I must conduct postmarket surveillance?
We will send you a letter (the postmarket surveillance order)
notifying you of the requirement to conduct postmarket surveillance. We
may require that you submit information about your device that will
allow us to better define the scope of a surveillance order. We will
specify the device(s) subject to the surveillance order and the reason
that we are requiring postmarket surveillance of the device under
section 522 of the act. We will also provide you with any general or
specific guidance that is available to help you develop your plan for
conducting postmarket surveillance.
Sec. 822.6 When will you notify me that I am required to conduct
postmarket surveillance?
We will notify you as soon as we have determined that postmarket
surveillance of your device is necessary, based on the identification
of a surveillance question. This may occur during the review of a
marketing application for your device, as your device goes to market,
or after your device has been marketed for a period of time.
Sec. 822.7 What should I do if I do not agree that postmarket
surveillance is appropriate?
If you do not agree with our decision to order postmarket
surveillance for a particular device, there are a number of mechanisms
you may use to request review of our decision. These include:
(a) Requesting a meeting with the Director, Office of Surveillance
and Biometrics, Center for Devices and Radiological Health, who
generally issues the order for postmarket surveillance;
(b) Seeking internal review of the order under 21 CFR 10.75;
(c) Requesting an informal hearing under 21 CFR part 16; or
(d) Requesting review by the Medical Devices Dispute Resolution
Panel of the Medical Devices Advisory Committee.
Subpart C--Postmarket Surveillance Plan
Sec. 822.8 When, where, and how must I submit my postmarket
surveillance plan?
You must submit your plan to conduct postmarket surveillance within
30 days of the date you receive the postmarket surveillance order. For
devices regulated by the Center for Devices and Radiological Health,
you should send three copies of your submission to the Center for
Devices and Radiological Health, Postmarket Surveillance Document
Center (HFZ-510), 1350 Piccard Dr., Rockville, MD, 20850. For devices
regulated by the Center for Biologics Evaluation and Research, you
should send three copies of your submission to Center for Biologics
Evaluation and Research, Document Control Center, 1401 Rockville Pike,
suite 200N, Rockville, MD 20852-1448. When we receive your original
submission, we will send you an acknowledgement letter identifying the
unique document number assigned to your submission. You should use this
number in any correspondence related to this submission.
Sec. 822.9 What must I include in my submission?
Your submission must include the following:
(a) Organizational/administrative information:
(1) Your name and address;
(2) Generic and trade names of your device;
(3) Name and address of the contact person for the submission;
(4) Premarket application/submission numbers for your device;
(5) Table of contents identifying the page numbers for each section
of the submission;
(6) Description of the device (this may be incorporated by
reference to the appropriate premarket application/submission);
(7) Product codes and a list of all relevant model numbers; and
[[Page 52389]]
(8) Indications for use and claims for the device;
(b) Postmarket surveillance plan;
(c) Designated person information:
(1) Name, address, and telephone number; and
(2) Experience and qualifications.
Sec. 822.10 What must I include in my surveillance plan?
Your surveillance plan must include a discussion of:
(a) The plan objective(s) addressing the surveillance question(s)
identified in our order;
(b) The subject of the study, e.g., patients, the device, animals;
(c) The variables and endpoints that will be used to answer the
surveillance question, e.g., clinical parameters or outcomes;
(d) The surveillance approach or methodology to be used;
(e) Sample size and units of observation;
(f) Sources of data, e.g., hospital records;
(g) The data collection plan and forms;
(h) The patient followup plan, if applicable;
(i) The procedures for monitoring conduct and progress of the
surveillance;
(j) An estimate of the duration of surveillance;
(k) All data analyses and statistical tests planned; and
(l) The content and timing of reports.
Sec. 822.11 What should I consider when designing my plan to conduct
postmarket surveillance?
You must design your surveillance to address the postmarket
surveillance question identified in the order you received. You should
also consider the function, operating characteristics, and intended use
of your device when designing a surveillance approach.
Sec. 822.12 Do you have any information that will help me prepare my
submission or design my postmarket surveillance plan?
We have issued guidance for the development of postmarket
surveillance plans which discusses the contents of a plan and points to
consider in developing one. We have also issued guidance on criteria
and approaches for postmarket surveillance, which discusses the
criteria that we use to determine when postmarket surveillance under
section 522 of the act is appropriate and necessary. The guidance
identifies and discusses a broad range of surveillance approaches and
describes the circumstances for which each would be suitable. These
guidance documents are available on the Internet and from the Center
for Devices and Radiological Health, Office of Surveillance and
Biometrics (HFZ-510), 1350 Piccard Dr., Rockville, MD 20850.
Sec. 822.13 [Reserved]
Sec. 822.14 May I reference information previously submitted instead
of submitting it again?
Yes, you may reference information that you have submitted in
premarket submissions as well as other postmarket surveillance
submissions. You must specify the information to be incorporated and
the document number and pages where the information is located.
Sec. 822.15 How long must I conduct postmarket surveillance of my
device?
The length of postmarket surveillance will depend on the postmarket
surveillance question identified in our order. We may order prospective
surveillance for a period up to 36 months; longer periods require your
agreement. If we believe that a prospective period of greater than 36
months is necessary to address the surveillance question, and you do
not agree, we will use our dispute resolution procedures.
Subpart D--FDA Review and Action
Sec. 822.16 What will you consider in the review of my submission?
First, we will determine that the submission is administratively
complete. Then, in accordance with the law, we must determine whether
the designated person has appropriate qualifications and experience to
conduct the surveillance and whether the surveillance plan will result
in the collection of useful data that will answer the surveillance
question.
Sec. 822.17 How long will your review of my submission take?
We will review your submission within 60 days of receipt.
Sec. 822.18 How will I be notified of FDA's decision?
We will send you a letter notifying you of our decision and
identifying any action you must take.
Sec. 822.19 What kinds of decisions may FDA make?
----------------------------------------------------------------------------------------------------------------
If your plan: Then we will send you: And you must:
----------------------------------------------------------------------------------------------------------------
(a) Should result in the collection An approval order, identifying any Conduct postmarket surveillance of
of useful data that will address specific requirements related to your device in accordance with the
the postmarket surveillance your postmarket surveillance approved plan.
question
(b) Should result in the collection An approvable letter identifying the Revise your postmarket surveillance
of useful data that will address specific revisions or information submission to address the concerns
the postmarket surveillance that must be submitted before your in the approvable letter and submit
question after specific revisions plan can be approved it to us within the specified
are made or specific information is timeframe. We will determine the
provided timeframe case by case, based on
the types of revisions or
information that you must submit.
(c) Does not meet the requirements A letter disapproving your plan and Revise your postmarket surveillance
specified in this part identifying the reasons for submission and submit it to us
disapproval within the specified timeframe. We
will determine the timeframe case
by case, based on the types of
revisions or information that you
must submit.
(d) Is not likely to result in the A letter disapproving your plan and Revise your postmarket surveillance
collection of useful data that will identifying the reasons for submission and submit it to us
address the postmarket surveillance disapproval within the specified timeframe. We
question will determine the timeframe case
by case, based on the types of
revisions or information that you
must submit.
----------------------------------------------------------------------------------------------------------------
[[Page 52390]]
Sec. 822.20 What are the consequences if I fail to submit a postmarket
surveillance plan, my plan is disapproved and I fail to submit a new
plan, or I fail to conduct surveillance in accordance with my approved
plan?
The failure to have an approved postmarket surveillance plan or
failure to conduct postmarket surveillance in accordance with the
approved plan constitutes failure to comply with section 522 of the
act. Your failure would be a prohibited act under section 301(q)(1)(B)
of the act, and your device would be misbranded under section 502(t)(2)
of the act. This means that we could seek to impose a number of
penalties, including civil money penalties, criminal penalties, seizure
of your products, or court injunction against further marketing of your
device.
Sec. 822.21 What must I do if I want to make changes to my postmarket
surveillance plan after you have approved it?
You must submit a request to make the proposed change and a revised
postmarket surveillance plan (if needed) and receive our approval prior
to making changes in your plan. You should identify this as a
supplement to your postmarket surveillance submission, citing the
unique document number that we assigned, and specifically identify the
changes to the plan and the reasons/justification for making the
changes in your cover letter.
Sec. 822.22 What recourse do I have if I do not agree with your
decision?
If you disagree with us about the content of your plan or if we
disapprove your plan, there are a number of mechanisms you may use to
request review of our decision. These include:
(a) Requesting a meeting with the Director, Office of Surveillance
and Biometrics, Center for Devices and Radiological Health, who
generally issues the order for postmarket surveillance;
(b) Seeking internal review of the order under 21 CFR 10.75;
(c) Requesting an informal hearing under 21 CFR part 16; or
(d) Requesting review by the Medical Devices Dispute Resolution
Panel of the Medical Devices Advisory Committee.
Sec. 822.23 Is the information in my submission considered
confidential?
We consider the content of your submission confidential until we
have approved your postmarket surveillance plan. After we have approved
your plan, the contents of the original submission and any amendments,
supplements, or reports may be disclosed in accordance with the Freedom
of Information Act. We will continue to protect trade secret and
confidential commercial information after your plan is approved. We
will not disclose information identifying individual patients. You may
wish to indicate in your submission which information you consider
trade secret or confidential commercial.
Subpart E--Responsibilities of Manufacturers
Sec. 822.24 What are my responsibilities when I am notified that I am
required to conduct postmarket surveillance?
You must submit your plan to conduct postmarket surveillance to us
within 30 days from receipt of the order (letter) notifying you that
you are required to conduct postmarket surveillance of a device.
Sec. 822.25 What are my responsibilities after my postmarket
surveillance plan has been approved?
After we have approved your plan, you must conduct the postmarket
surveillance of your device in accordance with your approved plan. This
means that you must ensure that:
(a) Postmarket surveillance is initiated in a timely manner;
(b) The surveillance is conducted in a scientifically sound manner
and with due diligence;
(c) The data identified in the plan is collected;
(d) Any reports required as part of your approved plan are
submitted to the agency in a timely manner; and
(e) Any information that we request prior to your submission of a
report or in response to our review of a report is provided in a timely
manner.
Sec. 822.26 If my company changes ownership, what must I do?
You must notify us within 30 days of any change in ownership of
your company. Your notification should identify any changes to the name
or address of the company, the contact person, or the designated person
(as defined in Sec. 822.3(b)). Your obligation to conduct postmarket
surveillance will generally transfer to the new owner, unless you have
both agreed that you will continue to conduct the surveillance. If you
will continue to conduct the postmarket surveillance, you still must
notify us of the change in ownership.
Sec. 822.27 If I go out of business, what must I do?
You must notify us within 30 days of the date of your decision to
close your business. You should provide the expected date of closure
and discuss your plans to complete or terminate postmarket surveillance
of your device. You must also identify who will retain the records
related to the surveillance (described in subpart G of this part) and
where the records will be kept.
Sec. 822.28 If I stop marketing the device subject to postmarket
surveillance, what must I do?
You must continue to conduct postmarket surveillance in accordance
with your approved plan even if you no longer market the device. You
may request that we allow you to terminate postmarket surveillance or
modify your postmarket surveillance because you no longer market the
device. We will make these decisions on a case-by-case basis, and you
must continue to conduct the postmarket surveillance unless we notify
you that you may stop your surveillance study.
Subpart F--Waivers and Exemptions
Sec. 822.29 May I request a waiver of a specific requirement of this
part?
You may request that we waive any specific requirement of this
part. You may submit your request, with supporting documentation,
separately or as a part of your postmarket surveillance submission to
the address in Sec. 822.7.
Sec. 822.30 May I request exemption from the requirement to conduct
postmarket surveillance?
You may request exemption from the requirement to conduct
postmarket surveillance for your device or any specific model of that
device at any time. You must comply with the requirements of this part
unless and until we grant an exemption for your device. Your request
for exemption must explain why you believe we should exempt the device
or model from postmarket surveillance. You should demonstrate why the
surveillance question does not apply to your device or does not need to
be answered for the device for which you are requesting exemption.
Alternatively, you may provide information that answers the
surveillance question for your device with supporting documentation to
the address in Sec. 822.7.
Subpart G--Records and Reports
Sec. 822.31 What records am I required to keep?
You must keep copies of:
(a) All correspondence with your investigators or FDA, including
required reports;
(b) Signed agreements from each of your investigators, when
applicable, stating the commitment to conduct the surveillance in
accordance with the
[[Page 52391]]
approved plan, any applicable FDA regulations, and any conditions of
approval for your plan, such as reporting requirements;
(c) Your approved postmarket surveillance plan, with documentation
of the date and reason for any deviation from the plan;
(d) All data collected and analyses conducted in support of your
postmarket surveillance plan; and
(e) Any other records that we require to be maintained by
regulation or by order.
Sec. 822.32 What records are the investigators in my surveillance plan
required to keep?
Your investigator must keep copies of:
(a) All correspondence with another investigator, FDA, or you,
including required reports.
(b) The approved postmarket surveillance plan, with documentation
of the date and reason for any deviation from the plan.
(c) All data collected and analyses conducted for postmarket
surveillance.
(d) Any other records that we require to be maintained by
regulation or by order.
Sec. 822.33 How long must we keep these records?
You and your investigators must keep all records for a period of 2
years after we have accepted your final report, unless we specify
otherwise.
Sec. 822.34 What must I do with the records if the sponsor of the plan
or an investigator in the plan changes?
If the sponsor of the plan or an investigator in the plan changes,
you must ensure that all records related to the postmarket surveillance
have been transferred to the new sponsor or investigator and notify us
within 10 days of the effective date of the change. You must provide
the name, address, and telephone number of the new sponsor or
investigator, certify that all records have been transferred, and
provide the date of transfer.
Sec. 822.35 Can FDA inspect my manufacturing site or other sites
involved in my postmarket surveillance plan?
We can review your postmarket surveillance programs during
regularly scheduled inspections, inspections initiated to investigate
recalls or other similar actions, and inspections initiated
specifically to review your postmarket surveillance plan. We may also
inspect any other person or site with postmarket surveillance
obligations, such as clinical investigators or contractors. Any person
authorized to grant access to a facility must permit authorized FDA
employees to enter and inspect any facility where the device is held or
where records regarding postmarket surveillance are held.
Sec. 822.36 Can FDA inspect and copy the records related to my
postmarket surveillance plan?
We may, at a reasonable time and in a reasonable manner, inspect
and copy any records pertaining to the conduct of postmarket
surveillance that are required to be kept by this part. You must be
able to produce records and information required by this part that are
in the possession of others under contract with you to conduct the
postmarket surveillance. We also expect those who have signed
agreements or are under contract with you to produce the records and
information upon our request. This information must be produced within
72 hours of the initiation of the inspection. We generally will redact
information pertaining to individual subjects prior to copying those
records, unless there are extenuating circumstances.
Sec. 822.37 Under what circumstances would FDA inspect records
identifying subjects?
We can inspect and copy records identifying subjects under the same
circumstances that we can inspect any records relating to postmarket
surveillance. The agency is likely to be interested in such records if
we have reason to believe that required reports have not been
submitted, or are incomplete, inaccurate, false, or misleading.
Sec. 822.38 What reports must I submit to FDA?
You must submit interim and final reports as specified in your
approved postmarket surveillance plan. In addition, we may ask you to
submit additional information when we believe that the information is
necessary for the protection of the public health and implementation of
the act. We will also state the reason or purpose for the request and
how we will use the information.
Dated: August 18, 2000.
Margaret M. Dotzel,
Associate Commissioner for Policy.
[FR Doc. 00-21827 Filed 8-28-00; 8:45 am]
BILLING CODE 4160-01-F