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DEPARTM EN T OF H EALTH & HU M AN SERVICES

Public Health Service
Food and Drug Admjnislratlon
1 0G03 New Hampshire Ave.
Silver Sprtrig, MD 20993-0002

April 1 1 , 201 3
VIA U NITED PARCEL SERVICE

James F. NIcGuckin, Jr., M .D .
Chief Operating Officer, Principal Investigator
1 450 Parkside Avenue, Unit 1 6
Trenton, NJ 08638
Dear Dr. McG uckiri:
The purpose of this letter is to inform you of the findings of a Food and Drug
Administration (FDA) inspection of your clinical site from July 2, 201 2, to July 20,
201 2, by investigators from the FDA New Jersey District Office. This inspection
was conducted to deterrhlne whether activities and procedures related to your
participation in the clinicai study titled, "Multi-center Registry of Chronic
Cerebrospinal Insufficiency Testing and Treatment," (the Hubbard Protocol)
compiled virith applicable federal regulations. The catheters and stents used in
this study are devices as defined in section 201 (h) of the Federal Food, Drug,
and Cosmetic Act (the Act), 21 U .S.C. § 321 (h), because they are intended for
use in the diagnosis of disease or other conditions or In the cure, mitigation,
treatment, or prevention of disease, or to affect the structure or function of the
body.
The clinical study is an investigation of a significant risk device, which means
FDA approval of an application for Investigational Device Exemption (IDE) is
required prior to commencement of the study. At the tim e you conducted the
investigation and as of the day this letter was signed, the study sponsor, the
Hubbard Foundation, had yet to obtain IDE approval from FDA, in violation of
section 520(g) of the Act. 21 U.S.C. § 360i(g) and 21 CFR 81 2.20 and 81 2.42.
The Inspection was conducted under a program designed to ensure that data
and information contained in requests for IDEs, Prem arket Approval applications,
and Premarket Notification subm issions are scientifically valid and accurate.
Another objective of the program is to ensure that hum an subjects are protected
from undue hazard or risk during the course of scientific investigations.
Our review of the Inspection report prepared by the district office revealed
several violations of Title 21 , Code of Federal Regulations (CFR) Part 81 2 -

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Investigational Device Exem ptions, and Part 50 - Protection of H uman Subjects,
wtiich concerns requirements prescribed under section 520(g) of the Act. 21
u s e . § 360j(g).
At the close of the inspection, the FDA Investigator presented an inspecticnal
observations Form FDA 483 for review and d is cu s s ^ the observations listed
the form vwth Laurie Brown, RN ES N (Study Coordinator an d Director of Clinic
Compliance), and Cynthia Gould, RN BSN (Center M anager). Th e deviations
noted on th e Form FDA 483, your written response dated August 9, 201 2, and
our review of the inspection report, are discussed below. Although you stated In
your August 9, 201 2. response that you Im mediately discontiriued any further
involvement with th e H ubbard Foundation after FD A's Inspection, we have the
following concerns with your response to the Form FDA 483, particularly because
your response alludes to participation In future studies. I t Is Imperatrve that these
issues be corrected should you choose to be Involved in this or another clinical
study of a device in th e future.
(1 . Failure to conduct the Investigation according to signed agreem ent, thai
investigational pian,^ap 9llcable FDA regu lations, and any conditions of}
'approval imposed) &iran In stitutional Review Board (LRB) or FDA. [2 1
iCFR 81 2.1 00. 21 CF Rqi2.1 1 0(b )lJ

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fAn investigator Is responsible for ensuring that an I nv^tig a tlo n is conducted]^
'according to the signed agreem ent, the investigational plan, and appilcabie FDAi
{regulations. In addition, an investigator Is responsible for ensuring that an^
investigation is conductinig according to ariy conditions of approval imposed by)
ithe IRB or FD A. The inspection conducted at your site revealed several!
instan ces where y o ^ k l n^ot adh ere to this fesponstbility. This failure can^i
Icompromlse the^fellabilH^.'of the data from th e study. The safety of h u m eri
subjects participating In the study may also be affe ^e d resultin g in increased risl<i
(of harm to thiem. Examples of this failure Include,' b u ta re not limited^to. jthe)
fq ljpwn g :'.
You did not obtain creatinine values to evaluate th e kidney function for at least 1 4^
^subjects, as stated on th e case report form s. Abnorm al kidney function Is a study/
^exclusion criteria set forth in the protocol.. Subjects with abnormal creatinine)
(values and probable abnormal kidney function may have been Improperly)
'enrolled in the study. As a result, these subjects would be at increased risk ofj
'developing.worsening, kidney disease or kidney failure.)
— - y
obtain^Magnetic Resonance Imaging (MR!) testing at 6,
'months for at le a stjl t'su bjects as stipulated In the protocol. Thls)^
com prom ised the safety of study subjects because tim ely MR! testing and)
(lbllQW_upj5an he lp mitigate certain risks such as hemorrhage and vascular)

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(r^tenosfs associated vnth the study. To ensure subject s d f^ , importar^
(diagnosttc tests like M RI should be performed accotding to the protocol.
Cb-^You did not report serious adverse events, which your staff identified as
'severe, for three subjects: worsening symptoms of depression (su bj^^
t1 001 ), fatigue and pressure in the back of the head (subject 1 009), and)
tallergic reaction (subject 1 1 21 040). The Investigator Statement of)
'Agreement with BioMed IRB and the IRB approval letter, dated March^d^
'201 1 . required reporting serious adverse events occurring at your site
^within 1 0 calendar days from the date of discovery by the investigator.
Reporting adverse events to the IRB Is important for ensuring the safety)
(and welfare of study subjects. These symptorns are clinically significant^
(as they may represent worsening disease or a new medical condition.)
^The IRB should be aware of this information as It helps it evaluate and)
decide whether changes need to be mEKte to the study to ensure subiert)
'safety.T~

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0. You did not file significant protocol deviations with the IRB. for significant
protocol deviations described in items a-c above, as required by the'
'.Investigator Statem ent of Agreement with BioM ed IRB. Protocol^ _
(deviations reports are important.components of the study that are als^
(needed to ensure subject safety. They should be filed u/ith the IRB in ^
'^m ely manner so lh at they can be reviewed an d appropriate action taken^

lif needed.r^

You did not report the June 30, 201 1 , clinical site closures for the J e rs ^
(City and Piscataway, New Jersey, sites to the IRB as instructed by th^
lIRB's site approval letter, dated March 30 201 1 . According to the)
(continuai approval notification, dated April 4. 201 2, these sites were still
Active in 201 2.)
6- Y ou used recruitm ent materials not approved by the IRB. The IRB V
r^quireTneTits^re'sti
in the Investigator Statement of Agreement)
iwith BioMed iRB:and the IRB approval letter, dated March 30, 2011 . YouFO
'(failure to secure IRB approval of recruitment materials prevented the IRBj
(from ensuring that the rights and welfare of study subjects are protected.)
AdheiBfice to the investigational plan, signed investigator agree ment, FDA
regulations, and IRB conditions helps ensure that research subjects will not be
exposed to known hazards that would place th em in jeopardy or invalidate the
outcome of the research. Your ad herence to the Investigational plan, investigator
agreement, and IRB approval requirements In future studies is important to
minimize unnecessary risks to subjects. Adherence to these requirements is
particularly important in; studies such as this, which involve invasive procedures
and a high risk study population with an unpredictabie course of disease.

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Page 4 - James F. McGuckin, Jr., M.D.

[Wo acknowledge that, in your August 9, 201 2, response you statedjhat
discontinued any furtfier invptvement with the Hubbard Foundation.'^ _____
iNevertheiess, we have particular concerns about your responses and correcti^
(actions, which pertain to the research subjects you treated under the Hubbardi
^Protocol as well as future studies in which you may choose to participated
(^Specificaliy, in your written response, you acknowledge the deficiencies notedi
(above and Indicate that^you have created a Clinical Research Manual to apply~t$
(all future studies in which Vascular Access Centers personnel participate. Also,^
lyou submitted a^c^eck-off'sheet signed by site staff to evidence that they hayej
£read and understand the new procedures. Section H4di of your new manual!
ititled.VThi^.Protection of H um an Subjects In Research," states th atplln ica i^
(laboratory testing will be performed within industry standard. We h^ej^pncern^
(about thjsjf^^pdnse^since clinical research must foliow the f^rptoppj,^
(investigatibnal plan, arid requirements of the reviewing IRB.'
In addition, Section B of the Clinical Research Man ual describes educatingi
research staff, but does not give sufficient detail about the training process or
(timing; when hiring new staff, in particular.- Moreover, your response does noti
laddress how the new manual will prevent the issues identified above from)
(^recurring.)

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\\Ne are also concerned that, ^ i t e Section 1 2.A of your Clinical Research Manual!
indicates that you will require IRB review of your promotionai materials, it does)
Cnot specify that^prbmpMnaJ ^materials must be approved by the iRB,before use^
i2._Fallur6 to en sure that inform ed consent was obtained in accordance)
with 21 CFR Part 50,FC21 CFR 81 2.1 00; 21 CFR S0.2S(a)(1 i ajid (6)1 )
(As an investigator, y o u j ^ responsible for protecting the rights, saifety, andi
(welfare of subjects^unde^ycur care by ensuring informed consent is obtained i ^
(accordance with 21 CFR Parts 50. You failed to ensure that informed consent)
(was obtained from subjects and documented in accordance.with these)
(fBguiations. Specifically, you used Informed consent documents that did n ^
(include the duration of subject participation ornotice that FDA may Inspect the)
(records.)
(A valid informed consent process ensures that before research subjects decide)
(to participate they have; a clear understanding of the length of their participation)
and who. may review or inspect their study records. Although you submitted a'
(corrected informed consent document, you did not provide a training plan that
(addresses.how you will implement revised procedures with your staff.)

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Page 5 - James F. McGuckin, Jr., M.D.
The violations described above are not intended to be an all-inclusive list of
problerhs that may exist with your clinical study. It is your responsibility as a
clinical investigator to ensure compliance with the Act and applicable regulations.
We will verify your corrective actions, in particular your assertion that you are no
longer conducting clinical studies, during our next inspection.
iWe request that you Identify all subjects who participated in the clinical protocoli
.supplied by the Hubbard.Foundation. Please also provide us with a copy of the^
(IRB-approved letter that informed subjects that the study referenced in tills lette^
i^has been closed. The letter should have included any pertinent information that^
(was missing from.the informed, consent document {I.e., the d i ^ ti p ri ^ su bj^ T
'participation and a notice that FDA may Inspect the records).)
iln addition, before engaging in any clinical studies In the future, please descrlb^
how your new manual will ensure that the training process Is adequate and that^
(any new staff will be trained as they are hired.. Provide FDA confirmatian
i ^ in i n g In human subject research for yourself and your research staff. F or[
(example, this may be accomplished by providing completed training certificates)
(that include the title of the training, the staff members trained, and date)
(completed. In addition, please correct your Clinical Research Manual to r^uire)
'new materials to be approved by the IRB before use. Please also provide)
documentation of ariy other actions that you have taken or will take to correal
these violations and to proveht the recurrence of similar violations In current o r)
future studies for which you are the clinical investlgator.r
Your response should reference "CTS # EC1 20360/E001 " and be sent to:
Attention: Anne T. Hawthorn
Food and Drug Administration
Ceriterfor Devices and Radiological Health
Office of Compliance
Division of Bioresearch.Monitoring
1 0903 New Hampshire Avenue
Building 66, Room 3504
Silver Spring, Maryland 20993-0002.
A copy of this letter has been sent to FDA's New Jersey District Office, 1 0
Waterview Blvd, Third Floor, Parsippany, NJ 07054. Please send a copy of your
response to that office.
You will find information to assist you In understanding your responsibilities and
planning your corrective actions in the FDA Information Sheets Guidance for
institutional Review Boards and Clinical Investigators, which can be found at
httD://www.fda.QGv/oc/ohrt/irfas/.

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Page 6 - James F. McGuckin, Jr., M.D.
The Division of Bioresearch Monitoring has developed introductory triaining
modules in FDA-regulated device clinical research practices, which are available
on the FDA website. The modules are forpersons Involved In FDA-regulated
device dlnical research activities. These modules are located at the following
^website address: httD://www.fda.aov/TralnlnQ/CDRHLearn/ucm1 6201 5.htm.
If you have any questions, please contact Anne Hawthorn at (301 ) 796-6561 or
Anne.Hawthorn@fda.hhs.aov.
Sincerely yours,

Steven D. Silverman
Director
OfTice of Compliance
Center for Devices and
Radiological Health

cc:
Hubbard Foundation
d o David Hubbard, MD
1 0065 Old Grove Rd. Suite 1 03
San Diego, CA 921 31 .
Blomed IRB
d o Holly Hunter Skull, IRB Chairman
7676 Hazard Center Drive, Suite 500
San Diego, CA 921 08

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