Document ID: FDA-2010-P-0176-0084
Agency: fda
Document Type: Notice
Title: SEDASYS Computer-Assisted Personalized Sedation System; Ethicon Endo-Surgery, Inc.'s Petition for Review of FDA's Denial of Premarket Approval - Notice of Meeting
Posted Date: 2011-11-21T05:00Z

[Federal Register Volume 76, Number 224 (Monday, November 21, 2011)]
[Notices]
[Pages 71980-71982]
From the Federal Register Online via the Government Printing Office [www.gpo.gov]
[FR Doc No: 2011-29888]

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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2010-P-0176]

SEDASYS Computer-Assisted Personalized Sedation System; Ethicon 
Endo-Surgery, Incorporated's Petition for Review of the Food and Drug 
Administration's Denial of Premarket Approval; Notice of Meeting

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice.

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    This notice announces a forthcoming meeting of a public advisory 
committee of the Food and Drug Administration (FDA). The topic to be 
discussed is the Center for Device and Radiological Health's (CDRH's) 
denial of a premarket approval application (PMA) for the SEDASYS 
computer-assisted personalized sedation system (SEDASYS) submitted by 
Ethicon Endo-Surgery Inc. (EES)--the sponsor for SEDASYS. The meeting 
will be open to the public.
    Name of Committee: Medical Devices Dispute Resolution Panel of the 
Medical Devices Advisory Committee.
    General Function of the Committee: To provide advice and 
recommendations to the Agency on scientific disputes between CDRH and 
sponsors, applicants, and manufacturers
    Date and Time: The meeting will be held on December 14, 2011, from 
8 a.m. to 6 p.m.
    Location: The meeting will be held at the Hilton Washington, DC/
North, Salons A, B, C, and D of the Ballroom, 620 Perry Pkwy., 
Gaithersburg, MD.
    Contact Person: Nancy Braier, Center for Devices and Radiological 
Health, Food and Drug Administration, 10903 New Hampshire Ave., Bldg. 
66, Rm. 5454, Silver Spring, MD 20993, (301) 796-5676, FAX: (301) 847-
8510, email: nancy.braier@fda.hhs.gov, or FDA Advisory Committee 
Information Line, 1-(800) 741-8138 (301) 443-0572 in the Washington, DC 
area), and follow the prompts to the desired center or product area. 
Please call the Information Line for up-to-date information on this 
meeting. A notice in the Federal Register about last minute 
modifications that affect a previously announced advisory committee 
meeting cannot always be published quickly enough to provide timely 
notice. Therefore, you should always check the Agency's Web site and 
call the appropriate advisory committee hot line/phone line to learn 
about possible modifications before coming to the meeting.
    Registration and Presentations: Interested persons may present 
data, information, or views, orally or in writing, on issues pending 
before the committee. Written submissions from persons other than EES 
and CDRH may be made to the docket on or before December 7, 2011. 
Submit electronic comments to http://www.regulations.gov. Submit 
written comments to the Division of Dockets Management (HFA-305), Food 
and Drug Administration, 5630 Fishers Lane, Rm. 1061, Rockville, MD, 
20852. It is only necessary to send one set of comments. It is no 
longer necessary to send two copies of mailed comments. Identify all 
written and electronic comments and submissions with the docket number 
found in brackets in the heading of this document. All written and 
electronic comments and submissions will be considered to be publicly 
disclosable.
    Oral presentations from persons other than EES and CDRH will be 
scheduled between approximately 8:15 to 8:45 a.m., and 2:15 to 2:45 
p.m. on December 14, 2011. If you wish to make an oral presentation 
during the meeting, you should register on or before November 30, 2011. 
Send registration information (including name, title, firm name, 
address, telephone, and FAX number), and requests to make oral 
presentations to Nancy Braier (see Contact Person). You should provide 
the docket number appearing in the heading of this notice. You also 
should submit a brief summary of the presentation, including the 
discussion topic(s) that will be addressed and the approximate time 
requested for your presentation. The amount of time to be allotted to 
each presenter may be limited to provide opportunities to as many 
persons wishing to present as possible. If the number of registrants 
requesting to speak is greater than can be reasonably accommodated 
during the scheduled open public hearing session, FDA may conduct a 
lottery to determine the speakers for that session. We encourage 
individuals and organizations with common interests to consolidate or 
coordinate their presentations to allow adequate time for each request 
for presentation. Nancy Braier will notify interested persons regarding 
their request to speak by December 5, 2011. On the day of the meeting 
scheduled open public speakers should identify themselves at the 
registration desk.
    After the scheduled speakers have spoken, the Chair of the advisory 
committee may ask them to remain if the advisory committee wishes to 
question them further. The Chair may recognize unscheduled speakers 
should time allow.

I. Background

    FDA is announcing that, in accordance with section 515(g)(2) of the 
Federal Food, Drug, and Cosmetic Act (FD&C Act) (21 U.S.C. 360e(g)(2)), 
a public advisory committee will review CDRH's denial of a PMA for the 
SEDASYS Computer-Assisted Personalized Sedation System submitted by 
EES--the sponsor for SEDASYS.
    On March 25, 2008, EES submitted a PMA (PMA P080009) for SEDASYS. 
SEDASYS is an integrated patient monitoring and drug delivery system. 
The device's proposed indication is for the intravenous administration 
of 1 percent (10 milligrams per milliliter (mg/mL)) propofol injectable 
emulsion for the initiation and maintenance of minimal-to-moderate 
sedation in adult patients (American Society of Anesthesiology physical 
status I and II) undergoing colonoscopy and esophagogastroduodenoscopy 
(EGD) procedures.
    At a May 28, 2009 meeting, the Anesthesiology and Respiratory 
Therapy Devices Panel met to discuss, and provide recommendations 
regarding, the PMA. The panel recommended, by a vote of 8-2, that the 
PMA be found ``approvable with conditions.''

[[Page 71981]]

    On February 26, 2010, CDRH issued a letter to EES indicating that 
PMA P080009 was not approvable under Sec.  814.44(f) (21 CFR 814.44(f)) 
because CDRH concluded that the data and information offered in support 
of the PMA did not provide a reasonable assurance that the device is 
safe under the conditions of use prescribed, recommended, or suggested 
in the proposed labeling, as required by section 515(d)(2)(A) of the 
FD&C Act.
    On March 25, 2010, EES requested review of the not approvable 
letter. Submitted in the form of a petition for reconsideration under 
21 CFR 10.33 (see Sec.  814.44(f)(2)), EES's petition stated that, in 
accordance with Sec.  814.44(f), EES considered the not approvable 
letter to be a denial of approval of PMA P080009 under Sec.  814.45 (21 
CFR 814.45). In accordance with section 515(d)(4) of the FD&C Act, EES 
requested review of this denial under section 515(g)(2) of the FD&C 
Act.
    Subsequently, on October 26, 2010, CDRH issued an order denying 
approval of the SEDASYS PMA (Denial Order), as required by Sec.  
814.45(e)(3). On November 5, 2010, in accordance with section 515(g)(2) 
of the FD&C Act, FDA granted EES's petition for review of the order 
denying PMA P080009.
    In accordance with section 515(g)(2) of the FD&C Act, the Office of 
the Commissioner referred PMA P080009 and the basis for the order 
denying its approval to the Medical Devices Dispute Resolution Panel, 
an advisory committee of experts established, in part, to receive 
referrals of petitions for advisory committee review under section 
515(g)(2)(B) of the FD&C Act. (See 76 FR 15321, March 21, 2011.) The 
advisory committee of experts for this review consists of nine persons, 
qualified by training and experience to evaluate the clinical and 
scientific basis of CDRH's order denying approval of the PMA. After 
independent study of the data and information furnished to it by the 
Office of the Commissioner, and other data and information before it, 
this advisory committee will submit to the Chief Scientist and Deputy 
Commissioner for Science and Public Health (Chief Scientist), the 
Commissioner's designee and an official authorized to perform all 
delegable functions of the Commissioner, a report and recommendation 
with respect to the order, together with the underlying data and 
information and a statement of the reasons or basis for the 
recommendation. (See section 515(g)(2)(A) of the FD&C Act.)
    The Office of the Commissioner will make the report and 
recommendation public in accordance with section 515(g)(2)(C) of the 
FD&C Act. The Office of the Commissioner will also provide a copy of 
that report and recommendation to EES and CDRH, and will offer EES and 
CDRH the opportunity to submit comments on the report and 
recommendation before a final order is rendered. In accordance with 
section 515(g)(2)(C) of the FD&C Act, the Chief Scientist will issue an 
order either affirming or reversing the order denying PMA P080009 and, 
if appropriate, approving or denying approval of the PMA.

II. Meeting Issues and Process

A. Issues

    Two major disputed clinical and scientific issues raised in CDRH's 
Denial Order are as follows: (1) Whether, given CDRH's view that, as it 
states in that order, ``the SEDASYS System is associated with an 
increased incidence of deeper-than-intended sedation'' in the pivotal 
study, the PMA provides a reasonable assurance that SEDASYS is safe for 
its proposed intended use by health care providers who have not been 
trained in the administration of general anesthesia; and (2) the 
adequacy and appropriateness of the control arm used by EES in the 
pivotal clinical trial for the device.
    Regarding the first issue, CDRH's Denial Order maintained that the 
data provided demonstrates that ``the SEDASYS System is associated with 
an increased incidence of deeper-than-intended sedation, including 
episodes of general anesthesia, compared to the `Current Standard of 
Care' arm that was used as a control.'' CDRH asserted in that order 
that it considered these observations to represent a ``serious safety 
signal'' that would require restricting use of the device to persons 
trained in the administration of general anesthesia. EES's position is 
that the five patients experiencing transient episodes of general 
anesthesia do not represent a safety concern because none experienced 
any apnea or oxygen desaturation, that the device has built-in safety 
features designed to avoid progression to apnea or oxygen desaturation, 
and that SEDASYS was associated with a significant reduction in the 
primary safety endpoint (AUCDesat), among other reasons.
    CDRH's Denial Order also maintained that EES's ``current proposal 
to mitigate the risks associated with the observed increased incidence 
of deeper-than-intended sedation, namely a targeted-training program, 
is inadequate because an outcome-based clinical study that would enable 
evaluation of the proposed training protocol has not been conducted.'' 
EES's petition for review of CDRH's Not Approvable determination 
countered that EES's proposed training program for SEDASYS ``is 
validated by the training the pivotal study investigators received 
prior to the start of the study and the outcomes of the study.''
    With respect to the control arm used in the clinical trial, EES's 
pivotal study was a non-blinded comparison of propofol administration 
by gastroenterology teams via SEDASYS with administration of 
benzodiazepine/opioid combinations by gastroenterology teams. CDRH 
maintains that, given the risks involved in administering propofol with 
SEDASYS that it believed were demonstrated in the pivotal study, the 
use of the device by the intended group of clinicians needs to be 
compared to propofol administration in a treatment arm without the 
device by health care professionals trained in the administration of 
general anesthesia, as contemplated by the drug labeling for propofol. 
EES's position is that the clinical trial design appropriately compares 
the device with the ``current standard of care''--benzodiazepine/opioid 
combinations--that it would supplant and provides reasonable assurance 
of safety and effectiveness.
    Questions for the advisory committee to consider relative to the 
safety issue are:
    1. Do the incidents of deeper-than-intended sedation observed in 
the SEDASYS pivotal trial, including general anesthesia in five 
patients in the SEDASYS group compared to one patient in the control 
group, represent a clinically significant safety concern?
    2. Do any probable benefits to health from use of SEDASYS outweigh 
any probable risks?
    3. Was the clinical trial comparing propofol administration by 
gastroenterology teams via SEDASYS with administration of 
benzodiazepine/opioid combinations by gastroenterology teams 
appropriate to determine whether there is a reasonable assurance that 
the device is safe for its proposed intended use?
    4. Should a clinical trial instead compare administration of 
propofol by gastroenterology teams via SEDASYS with administration of 
propofol without the device by persons trained in the administration of 
general anesthesia?
    5. Does the PMA demonstrate that the training EES proposed for the 
intended user group adequately addresses the risk of incidents of 
deeper-than-intended sedation, including the incidents of general 
anesthesia seen in the pivotal

[[Page 71982]]

trial, and the possible consequences of these events?
    6. Does the training program need to be validated to ensure that it 
adequately mitigates such risks, and, if so, how could this be done?

B. Process

    Although no statute or regulation requires that separation of 
functions be applied to this proceeding, the Agency is observing 
separation of functions as a matter of policy in this matter. As the 
Center responsible for the action under review, CDRH will be, like EES, 
a party to the advisory committee meeting and will be responsible for 
presenting its position at that meeting.
    In addition, as a corollary to its decision to observe a separation 
of functions, until the Commissioner issues an order either affirming 
or reversing the order denying approval of PMA P080009, the Office of 
the Commissioner will not engage in any ex parte communication (see 21 
CFR 10.3(a)) with anyone participating as a party or any person outside 
the Agency with respect to the matter under consideration. Any written 
ex parte communication has been and will continue to be immediately 
served on the two parties and filed in the docket. Any oral ex parte 
communication has been and will continue to be immediately memorialized 
in writing, served on both parties, and filed in the docket.
    At the meeting, each party will be provided 2 hours during the 
first portion of the meeting to present relevant information or views 
orally. The parties may use the allotted time as desired, consistent 
with an orderly meeting, and may be accompanied by additional persons, 
who may present relevant information or views. The parties will 
subsequently be allowed 15 minutes for rebuttal. During the advisory 
committee's open discussion, the advisory committee members may pose 
questions to, or requests for clarification from, EES and/or CDRH. 
Thereafter, each party will be allocated 15 minutes for summation, 
after which advisory committee deliberation and voting will occur.
    FDA welcomes the public's attendance at this advisory committee 
meeting and will make every effort to accommodate persons with physical 
disabilities or special needs. If you need special accommodations due 
to a disability, please contact Nancy Braier (see Contact Person) at 
least 7 days in advance of the meeting.
    FDA is committed to the orderly conduct of its advisory committee 
meetings. Please visit our Web site at http://www.fda.gov/AdvisoryCommittees/AboutAdvisoryCommittees/ucm111462.htm for procedures 
on public conduct during advisory committee meetings.
    Because this is a public meeting before an advisory committee, it 
is subject to our regulations concerning the policy and procedures for 
electronic media coverage of public agency administrative proceedings 
(Sec. Sec.  10.200 through 10.206 (21 CFR 10.200 through 10.206)). 
These procedures are primarily intended to expedite media access to our 
public proceedings. Representatives of the electronic media may be 
permitted, subject to certain limitations, to videotape, film, or 
otherwise record our public administrative proceedings, including the 
testimony of witnesses in the proceedings. Accordingly, the parties and 
nonparty participants, and all other interested persons, are directed 
to Sec.  10.200 through 10.206, for a more complete explanation of 
those regulations' effect on this meeting.
    All documents filed or posted in this matter are available for 
public review under Docket No. FDA-2010-P-0176 in the Division of 
Dockets Management (see Registration and Presentations) between 9 a.m. 
and 4 p.m., Monday through Friday. Persons with access to the Internet 
may obtain documents at http://www.regulations.gov. FDA intends to make 
background material, including briefing materials for the advisory 
committee provided by CDRH and EES, available to the public no later 
than 2 business days before the meeting. If FDA is unable to provide 
the background material prior to the meeting, the background material 
will be made publicly available at the location of the advisory 
committee meeting, and the background material will be available in the 
Division of Dockets Management (see Registration and Presentations) and 
at http://www.regulations.gov after the meeting.
    Notice of this meeting is given under the Federal Advisory 
Committee Act (5 U.S.C. app. 2).

III. Transcripts

    Please be advised that as soon as a transcript is available, it 
will be accessible at http://www.regulations.gov. It may be viewed at 
the Division of Dockets Management (HFA-305), Food and Drug 
Administration, 5630 Fishers Lane, Rm. 1061, Rockville, MD.

    Dated: November 14, 2011.
Leslie Kux,
Acting Assistant Commissioner for Policy.
[FR Doc. 2011-29888 Filed 11-18-11; 8:45 am]
BILLING CODE 4160-01-P