[Federal Register: January 27, 2010 (Volume 75, Number 17)] [Notices] [Page 4402-4406] From the Federal Register Online via GPO Access [wais.access.gpo.gov] [DOCID:fr27ja10-98]
———————————————————————–
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.
———————————————————————–
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
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
https://www.ConnectLive.com/events/fda021810. Closed captioning for this
webcast will be available at https://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 https://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 https://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
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 https://
www.regulations.gov. This information will also be available at https://
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
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 https://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
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 https://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 https://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
