[Federal Register Volume 75, Number 17 (Wednesday, January 27, 2010)]
[Notices]
[Pages 4402-4406]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2010-1620]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2010-N-0054]


Strengthening the Center for Devices and Radiological Health's 
510(k) Review Process; Public Meeting; Request for Comments

AGENCY: Food and Drug Administration, HHS.

ACTION:  Notice of public meeting; request for comments.

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    The Food and Drug Administration (FDA) is announcing a public 
meeting entitled ``Strengthening the Center for Devices and 
Radiological Health's 510(k) Review Process.'' The purpose of the 
public meeting is to identify actions that the Center for Devices and 
Radiological Health (CDRH) can consider taking to strengthen the 
premarket notification process for review of medical devices, also 
known as the 510(k) process. FDA is seeking input on a number of 
identified challenges associated with the 510(k) process and is 
requesting comments on this topic.
    Dates and Time: The public meeting will be held on February 18, 
2010, from 8 a.m. to 5:30 p.m. Persons interested in attending and/or 
participating in the meeting must register by 5 p.m. on

[[Page 4403]]

February 12, 2010. Submit electronic or written comments by March 5, 
2010.
    Location: The public meeting will be held at the Hilton Washington 
DC North/ Gaithersburg, 620 Perry Pkwy., Gaithersburg, MD 20877. A live 
webcast of this meeting will be viewable on the day of the meeting at 
http://www.ConnectLive.com/events/fda021810. Closed captioning for this 
webcast will be available at http://www.speche.com/sbload.aspx?Load=Web,All,New&Height=90%25&Width=100%25&ClientID=31213.
    Contact Person: James Swink, Food and Drug Administration, Center 
for Devices and Radiological Health, 10903 New Hampshire Ave., Bldg. 
66, rm. 1609, Silver Spring, MD 20993, 301-796-6313, e-mail: 
james.swink@fda.hhs.gov.
    Registration: If you wish to attend the public meeting, you must 
register online at http://www.fda.gov/MedicalDevices/NewsEvents/WorkshopsConferences/default.htm (select the appropriate meeting from 
the list). Provide complete contact information for each attendee, 
including: Name, title, affiliation, address, e-mail, and telephone 
number. Registration requests should be received by February 12, 2010.
    If you wish to make an oral presentation during any of the open 
comment sessions at the meeting (see section II of this document), you 
must indicate this at the time of registration. FDA has included 
general discussion topics and specific questions for comment in section 
III of this document. You should also identify which discussion topic 
you wish to address in your presentation. In order to keep each open 
session focused on the discussion topic at hand, each oral presentation 
should address only one discussion topic. FDA will do its best to 
accommodate requests to speak. Individuals and organizations with 
common interests are urged to consolidate or coordinate their 
presentations, and to request time for a joint presentation. FDA will 
determine the amount of time allotted to each presenter and the 
approximate time that each oral presentation is to begin.
    If you would like to participate in the planned end-of-day round-
table discussion (see section II of this document), you must indicate 
this at the time of registration, and also submit a brief statement 
that describes your experience with the 510(k) program. FDA is seeking 
participants interested in engaging in an end-of-day round-table 
discussion reflecting on the presentations given earlier in the day. 
The round-table discussion will include no more than 10 non-FDA 
participants. Only one participant from an organization or company will 
be assigned to the discussion group. FDA will attempt to have a range 
of constituencies participate in the discussion group. Others in 
attendance at the public meeting will have an opportunity to listen to 
the discussion.
    Registration is free and will be on a first-come, first-served 
basis. Early registration is recommended because seating is limited. 
FDA may limit the number of participants from each organization based 
on space limitations. Registrants will receive confirmation once they 
have been accepted. Onsite registration on the day of the public 
meeting will be provided on a space-available basis beginning at 7 a.m.
    If you need special accommodations due to a disability, please 
contact James Swink at 301-796-5610, james.swink@fda.hhs.gov at least 7 
days in advance of the public meeting.
    Comments: FDA is holding this public meeting to obtain information 
on a number of questions regarding the 510(k) process. The deadline for 
submitting comments related to this public meeting is March 5, 2010.
    Regardless of attendance at the public meeting, interested persons 
may submit electronic or written comments. Submit electronic comments 
to http://www.regulations.gov. Submit a single copy of electronic 
comments or two paper copies of any mailed comments, except that 
individuals may submit one paper copy. Submit written comments to the 
Division of Dockets Management (HFA-305), Food and Drug Administration, 
5630 Fishers Lane, rm. 1061, Rockville, MD 20852. Comments are to be 
identified with the docket number found in brackets in the heading of 
this document. In addition, when responding to specific questions as 
outlined below, please identify the question you are addressing. 
Received comments may be seen in the Division of Dockets Management 
between 9 a.m. and 4 p.m., Monday through Friday.

SUPPLEMENTARY INFORMATION:

I. Background

    The premarket notification (or 510(k)) process for the review of 
medical devices was established under the Medical Device Amendments of 
1976 (MDA) to the Federal Food, Drug, and Cosmetic Act (act). A post-
MDA device may be legally marketed without an approved premarket 
approval application (PMA) if FDA concludes, through review of a 510(k) 
submission (unless the device is exempt from this submission 
requirement), that the device meets the comparative standard of 
``substantial equivalence'' to a ``predicate'' device. By regulation, 
substantial equivalence may be determined by a comparison to a device 
that was legally marketed prior to May 28, 1976 (a pre-amendments 
device), or a device which has been reclassified from class III to 
class II or I (the predicate), or a device which has been found to be 
substantially equivalent through the 510(k) premarket notification 
process. (21 CFR 807.92(a)(3)).
    Congress enacted the Safe Medical Devices Act of 1990 (SMDA) to 
define ``substantial equivalence'' consistent with the agency's 
administration of the 510(k) program. ``Substantial equivalence'' 
means, with respect to a device being compared to a predicate device, 
that the device has the same intended use as the predicate device and 
that the FDA by order has found the device either has the same 
technological characteristics as the predicate device, or has different 
technological characteristics and the information submitted that the 
device is substantially equivalent to the predicate device contains 
information, including appropriate clinical or scientific data if 
deemed necessary by the FDA, that demonstrates that the device is as 
safe and effective as a legally marketed device and does not raise 
different questions of safety and effectiveness than the predicate 
device. (Section 513(i)(1)(A) of the act (21 U.S.C. 360c(i)(1)(A))).
    The current 510(k) program reflects the statutory framework and 
FDA's implementation of that framework. It is intended to meet two 
important public health goals: To make available to consumers devices 
that are safe and effective, and to promote innovation in the medical 
device industry. The 510(k) premarket notification process provides a 
mechanism for the classification of a device that is found to be 
substantially equivalent to a predicate device that does not require 
premarket approval. Over the past several years, concerns have been 
raised about whether the 510(k) program optimally achieves its intended 
goals.
    In light of these concerns, FDA commissioned the Institute of 
Medicine (IOM) to conduct an independent review of the program and, if 
necessary, to recommend administrative, regulatory, and/or statutory 
changes. Given that the IOM study is not expected to conclude until 
March 2011, CDRH has also convened an internal 510(k) Working Group to 
recommend possible actions that CDRH could take in the short term to 
strengthen the program, and to identify longer term

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options FDA could consider to strengthen the program.

II. Public Meeting

    The objective of this public meeting is to receive public input on 
key challenges related to the 510(k) program, focusing on the following 
four areas: (1) Issues related to predicate devices, (2) issues related 
to new technologies and scientific evidence, (3) issues related to 
practices CDRH has adopted in response to a high volume of 
510(k)submissions, and (4) issues related to postmarket surveillance 
and new information about marketed devices.
    During the meeting, FDA staff will present a brief overview of each 
of the areas of challenge listed previously. Each of the four FDA 
presentations will be followed by an open comment session, during which 
members of the public may present oral comments related to the topic 
under discussion. Specific questions related to each discussion topic 
are listed below (see section III of this document). As described 
previously, individuals who are interested in making an oral 
presentation during any of the open comment sessions must indicate this 
at the time of registration and must also identify which discussion 
topic they intend to address (see the Registration section of this 
document). In order to keep each open session focused on the discussion 
topic at hand, each oral presentation should address only one 
discussion topic. Commentators are free to submit written comments on 
any discussion topic(s) to the open docket (see the Comment section of 
this document). FDA will schedule speakers for each open session as 
time permits.
    After the four open comment sessions, the meeting will close with a 
round-table discussion between FDA staff and selected participants 
representing a range of constituencies (for more information about 
participating in the round-table discussion, see the Registration 
section of this document). The participants in the round-table 
discussion will reflect on the day's presentations, engage in a 
dialogue with each other and FDA staff, and provide closing thoughts. 
The participants will not be asked to develop consensus opinions during 
the discussion, but rather to provide their individual perspectives. 
Others in attendance at the meeting will have an opportunity to listen 
to the round-table discussion.
    In advance of the meeting, additional information, including a 
meeting agenda with a speakers' schedule for each open comment session, 
will be made available on the Internet. This information will be placed 
on file in the public docket (docket number found in brackets in the 
heading of this document), which is available at http://www.regulations.gov. This information will also be available at http://www.fda.gov/MedicalDevices/NewsEvents/WorkshopsConferences/default.htm 
(select the appropriate meeting from the list).

III. Issues for Discussion

    The discussion of the four general topics described in the 
following section of this document should not be limited by current 
statutes or regulations, as the recommendations the 510(k) Working 
Group develops may include recommendations for changes to current law.

A. Issues Related to Predicate Devices

    1. FDA maintains a searchable online database to provide interested 
parties, including prospective 510(k) submitters, with information 
about devices that have been cleared for marketing through the 510(k) 
process. Currently, if a device has been cleared, CDRH's Office of 
Device Evaluation (ODE) and Office of In-Vitro Diagnostics (OIVD) post 
online FDA's ``Substantially Equivalent'' (SE) letter to the 510(k) 
submitter with the Indications for Use page for the device, as well as 
the 510(k) Summary (written by the 510(k) submitter) or the 510(k) 
Statement for the 510(k) (as specified by 21 CFR 807.93) (see 21 CFR 
807.87(h)). OIVD also posts a ``decision summary'' (written by FDA 
reviewers) which includes a summary of submitted data and a comparison 
of the device to the predicate(s). With respect to the information 
described previously, please comment on the following:
    a. How effective is the 510(k) database and search engine in 
helping prospective submitters find and evaluate the adequacy of 
predicate devices for 510(k) submissions, and write substantial 
equivalency rationales? What aspects of the database and search engine 
are useful? What could be improved? What, if anything, should be added 
to the 510(k) database and search engine?
    b. How effectively do the publicly released documents listed 
previously describe the cleared indications for use of each device, the 
technological characteristics of the device, and the methods and type 
of information that were used to determine substantial equivalence to 
the device's predicate(s)? If these documents are not sufficient, 
please describe what additional information or documentation would be 
useful to interested parties.
    c. Should FDA require 510(k) holders who receive a substantial 
equivalence decision for their device to submit a redacted version of 
their 510(k) submission after clearance, for public release? Please 
explain why or why not.
    2. Some 510(k) submitters do not accurately portray the 
similarities and differences between the device under review and the 
predicate device(s). It is unclear whether this problem is due to the 
submitters' lacking complete information about devices that have been 
cleared previously and may be used as predicates, or whether there are 
other contributing factors. Please comment on this problem and what 
steps FDA should take to address it.
    3. Generally, a device that has a clearance under the 510(k) 
process may be used as a predicate, regardless of whether or not the 
device is still in use, remains relevant to current standards of care, 
or has been replaced by new technology. Please comment on the utility 
of this generally inclusive strategy and its positive or negative 
impact on achieving the two public health goals of the 510(k) program. 
Should there be stricter criteria for what predicate devices are 
eligible for use in new 510(k) submissions? If so, what criteria should 
be used, and how should those criteria be defined so that they can be 
consistently and effectively applied? Where possible, please also 
provide specific examples of cases in which the use of an ``outdated'' 
predicate device may have been beneficial or problematic.
    4. Incremental device changes may seem innocuous individually 
(i.e., in one 510(k) submission), but over time such changes may 
accumulate to create a device that is significantly different from the 
original device (referred to as ``predicate creep''). Similarly, 
clinical non-inferiority studies may be submitted as evidence of 
substantial equivalence between a device under review and a predicate. 
When a series of such studies is conducted over time (i.e., device B is 
non-inferior to A, device C is non-inferior to B, and device D is non-
inferior to C), the difference in effectiveness between device A and D 
may approach clinical significance (referred to as ``non-inferiority 
creep''). Please comment on what if any changes should be made to the 
510(k) program based on the occurrence of predicate creep and non-
inferiority creep. Are there circumstances under which FDA should 
consider a more thorough review of multiple incremental device changes 
between 510(k) submissions, or a more thorough review of the 
appropriateness of clinical non-inferiority studies when

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assessing differences in device safety and effectiveness? Please 
explain.
    5. In some cases, more than one predicate device has been submitted 
by the 510(k) submitter in its evaluation of substantial equivalence. 
For example, if there is not a single predicate device that has the 
same indication for use and technological characteristics as the device 
under review, a submitter may cite one predicate device in an effort to 
demonstrate the same intended use, and a different predicate device in 
an effort to demonstrate the same technological characteristics. The 
use of more than one predicate in this manner, in an effort to 
demonstrate substantial equivalence, has been referred to as using a 
``split predicate.'' When a submitter uses a split predicate, the 
``new'' device may be very different from any other device on the 
market. In other instances, a submitter has used more than one 
predicate device in the hope that each predicate individually (not 
combined with the other predicate) supports substantial equivalence. 
Please comment on whether the use of a split predicate or more than one 
predicate serves the public health goals of the 510(k) program. If 
possible, please include examples.
    6. To find that a device is substantially equivalent, FDA must 
determine, among other things, whether or not a new device has the same 
``intended use'' as the predicate device (Section 513(i) of the act). 
FDA uses a standardized series of questions, organized into a flowchart 
(available at http://www.fda.gov/downloads/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/UCM081395.pdf), to guide 
all 510(k) reviews. Currently, the flowchart distinguishes between an 
``indication for use'' and an ``intended use'': A device under review 
may have a different ``indication for use'' than the predicate, yet 
still be determined to have the same ``intended use'' and therefore may 
be found substantially equivalent.
    a. Please describe your understanding of an ``indication for use'' 
as compared to an ``intended use.'' Please describe what criteria, if 
any, FDA should use to determine whether or not to consider a different 
``indication for use'' to be a different ``intended use.'' Please 
provide examples of different ``indications for use'' that you believe 
should or should not be considered different ``intended uses'' and 
explain your reasoning.
    b. What are the advantages and disadvantages of distinguishing 
between the terms ``indication for use'' and ``intended use'' during 
the review process? What are the advantages and disadvantages of 
combining these concepts into one term?

B. Issues Related to New Technologies and Scientific Evidence

    1. Section 513(i) of the act defines the term ``different 
technological characteristics'' as ``a significant change in the 
materials, design, energy source, or other features of the device from 
those of the predicate device.'' Without regard to the statutory 
definition, what ``other features'' should FDA consider (or not 
consider) to be ``different technological characteristics''? If you do 
not believe any other features should be considered different 
technological characteristics, please state why.
    2. When a 510(k) submitter receives a Not Substantially Equivalent 
(NSE) determination from FDA, the submitter may petition FDA, if this 
type of device has not been approved through the PMA process, to 
classify this new type of device through the Evaluation of Automatic 
Class III Designation (or de novo) process. FDA may classify such a 
device as Class I is if the device type is generally of low risk and 
general controls are determined to be adequate to provide reasonable 
assurance of safety and effectiveness, or as Class II if special 
controls can be developed and are adequate, along with general 
controls, to provide reasonable assurance of safety and effectiveness 
for the device type. What criteria should FDA use to determine which 
risks can be mitigated through general controls alone or with special 
controls, and which risks are sufficient to make the device ineligible 
for de novo classification?
    3. If a device under review has ``different technological 
characteristics'' than the predicate(s), it may still be determined to 
be substantially equivalent if ``the information submitted that the 
device is substantially equivalent to the predicate contains 
information, including appropriate clinical or scientific data if 
deemed necessary by the [FDA] * * *, that demonstrates the device is as 
safe and effective as a legally marketed device and (II) [the device 
under review] does not raise different questions of safety and 
effectiveness than the predicate device'' (section 513(i) of the act). 
How should FDA identify and characterize the risks associated with a 
new technology that do not raise ``different questions of safety and 
effectiveness?'' Are there types of new technology that should not be 
considered appropriate to be cleared for market through the 510(k) 
process? Should FDA define ``different questions of safety and 
effectiveness?'' If so, please provide suggestions for such a 
definition.
    4. In some circumstances, FDA may consider data from one of the 
following four types of comparison studies, or a combination of any of 
them, to determine whether a new device is substantially equivalent to 
a predicate device: (1) A comparison of specifications to an FDA-
recognized standard; (2) a comparison of specifications through bench 
testing; (3) a comparison of specifications through bench and animal or 
bench and clinical testing; or (4) a comparison of specifications 
through bench, animal, and clinical testing.
    a. For each particular type of comparison, describe when the 
comparison is appropriate for a new device.
    b. When clinical testing is deemed necessary, such testing is often 
used to determine whether a device is at least as safe and effective as 
the predicate (i.e., no worse than the predicate by a small, clinically 
insignificant difference called the non-inferiority margin). If the 
device is not expected to perform any better than the predicate, then a 
large sample size may be necessary to show non-inferiority in 
accordance with the small margin. By contrast, clinical studies 
conducted to demonstrate superiority to a control, instead of non-
inferiority to a predicate, may require a relatively small sample size. 
Considering that devices under the 510(k) program may represent 
relatively minor changes compared with a predicate, are there 
circumstances under which one could show that a device is at least as 
safe and effective as the predicate without the need to conduct a large 
non-inferiority study? Please explain.
    c. The previous comparisons in (2), (3), and (4) each require some 
type of testing. Under what circumstances should such testing be 
performed on the new device alone, and under what circumstances should 
such testing be performed on the new device in addition to a predicate 
device as a concurrent comparison? Are there circumstances when a 
clinical study that does not use the predicate device as the comparator 
(e.g., uses a standard of care or a reference method instead) would be 
appropriate to evaluate substantial equivalence? Please explain.
    5. Some 510(k) submitters do not always initially provide 
sufficient engineering and design information for their devices under 
review, to enable FDA to have a sufficient understanding of how the 
device operates, and whether there are any design issues that would 
prevent it from operating as intended. Has FDA established sufficiently 
clear

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guidelines concerning the provision of such information in 510(k) 
submissions? If not, what additional guidance might be helpful?
    6. Section 513(f)(5) of the act (21 U.S.C. 360c(f)(5)) states that 
FDA may not withhold an initial classification determination based on 
``a failure to comply with any provision of the act unrelated to a 
substantial equivalence decision,'' including current good 
manufacturing practice (cGMP) requirements, unless there is a 
substantial likelihood that such failure will potentially present a 
serious risk to human health. Would it be beneficial for FDA to have 
greater authority to withhold an initial classification determination 
based on a failure to comply with cGMP requirements or other provisions 
of the act? Please explain.
    7. Currently, some 510(k) submissions include as the ``indication 
for use'' a device function that is not associated with a specific 
clinical utility (e.g., treatment or diagnosis of a specific 
condition).
    a. For new devices, should a requirement of the 510(k) program be 
that a device's ``indication for use'' be proven to FDA to provide 
clinical utility?
    b. Please provide examples of devices whose ``indications for use'' 
statements do not describe a clinical utility, and whether this may be 
beneficial, harmful, or neither. Examples may include devices that are 
capable of monitoring or measuring a new physiologic parameter that has 
no standard clinical context, or tool-type devices such as scalpels or 
lasers that may be cleared to cut and coagulate tissue.
    8. How effective is FDA's current implementation of section 
513(i)(1)(E) of the act with respect to curbing off-label use that 
could cause harm? The current implementation is described in 
``Determination of Intended Use for 510(k) Devices; Guidance for CDRH 
Staff (Update to K98-1)'' which is available at http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/ucm082162htm. Without regard to current law, should FDA consider 
modifying its approach? Please explain why or why not. If FDA should 
consider modifying its approach, how should FDA modify it?

C. Issues Related to Practices CDRH has Adopted in Response to a High 
Volume of 510(k) Submissions

    FDA receives a very large number of 510(k) submissions each year. 
In response to this high volume of work, CDRH has adopted a number of 
practices to allow for less resource-intensive reviews, including the 
third party review program, the Special 510(k) under the 510(k) 
Paradigm, bundling of devices in 510(k) submissions, and reliance on 
510(k) submitters' assertions of conformance to recognized standards 
(as in the Abbreviated 510(k) program). Due to resource constraints, 
CDRH often must rely on a single reviewer to assess each 510(k) 
submission. Please comment on the advantages and disadvantages of each 
of these practices, as related to the quality and timeliness of 510(k) 
reviews.

D. Issues Related to Postmarket Surveillance and New Information about 
Marketed Devices

    1. FDA generally does not require postmarket surveillance studies 
as a condition of medical device 510(k) clearance. Without regard to 
current law, please comment on whether or not it might be beneficial 
for FDA to impose such studies as a condition of medical device 510(k) 
clearance.
    2. Without regard to current law, should FDA allow for the 
rescission of 510(k) clearance decisions under a broad range of 
circumstances? If so, what specific criteria might justify the 
rescission of a 510(k) clearance decision?
    3. FDA obtains a significant amount of postmarket information for 
510(k)-cleared devices, including adverse event reports, recalls, and 
inspectional findings. Without regard to current law, should such 
information influence the premarket 510(k) review of similar devices? 
If so, how?
    4. FDA regulations require the submission of proposed labeling 
(including indications for use, directions for use, precautions, 
warnings, and contraindications) in a 510(k) prior to clearance of a 
device. However, 510(k) holders sometimes alter the labeling after 
clearance, so that the final printed labeling is different from that 
submitted to FDA in the 510(k). Please comment on whether or not it 
might be beneficial for FDA to review and clear the final printed 
labeling for all 510(k) devices or for selected 510(k) devices prior to 
marketing.
    5. FDA does not always know when there has been a purchase, sale, 
or transfer of ownership of a 510(k) for a particular device. Even 
though the new owner of the 510(k) is required to register and list, 
FDA may not be aware that the ownership of the 510(k) for the device 
has legally transferred. Should FDA exercise more authority in this 
area? If so, how?

IV. Transcripts

    Transcripts of the public meeting may be requested in writing from 
the Freedom of Information Office (HFI-35), Food and Drug 
Administration, 5600 Fishers Lane, rm. 6-30, Rockville, MD 20857, 
approximately 15 working days after the public meeting at a cost of 10 
cents per page. A transcript of the public meeting will be available on 
the Internet at http://www.regulations.gov.

    Dated: January 22, 2010.
David Dorsey,
Acting Deputy Commissioner for Policy, Planning and Budget.
[FR Doc. 2010-1620 Filed 1-22-10; 4:15 pm]
BILLING CODE 4160-01-S