Medical Devices SOP - Medical Devices by tyndale

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									Program for the Protection of Human Subjects (PPHS)
Devices: Policies and Procedures
Purpose
The purpose of this policy is to establish procedures for the Program for the Protection of
Human Subjects (PPHS/IRB) and Investigators when researchers wish to use a device in the
context of research (or when the use of a device has been designated to require IRB review)

Background
Before a device that is not approved by the Food and Drug Administration can be used in
human research, certain processes need to occur. These processes involve various parties,
including Sponsors, Investigators, IRB’s, and the FDA. Different factors can lead to different
pathways toward approved use of an unapproved device. This section will provide definitions,
explanations, and guidance on how the processes work.

Classes of Devices
The FDA classifies devices into three categories, Class I, II, and III. The FDA classification of a
device is determined by the amount of regulation necessary to provide a reasonable assurance
of safety and efficacy.

        Class I devices present minimal potential for harm to the user and are often simpler in
         design than Class II or Class III devices. Class I devices are subject to the least
         regulatory control. Examples of Class I devices include elastic bandages, examination
         gloves, and hand-held surgical instruments.
        Class II devices are those for which stricter regulatory controls are required to assure
         safety and effectiveness. Devices in Class II are held to a higher level of control than
         Class I devices. These special controls may include special labeling requirements,
         performance standards, and post market surveillance. The FDA considers that these
         controls are sufficient. Devices in this class are typically non-invasive and will perform
         as indicated and will not cause injury or harm to a patient or user. Examples of Class II
         devices include powered wheelchairs, infusion pumps, and surgical drapes.
        Class III devices are those that support or sustain human life, are of substantial
         importance in preventing impairment of human health, or which present a potential,
         substantial risk of illness or injury.1 Examples of Class III devices include replacement
         heart valves, silicone gel-filled breast implants, and implantable pacemakers.

FDA Device Approval Process
Once a device is developed, before the device can be marketed, the sponsor must first submit
to the FDA a pre-market notification, or 510(k), to determine if the new device is substantially
equivalent to a device already placed into one of the three device classification categories. If
the new device is deemed to be substantially equivalent to a current device, it may be marketed
immediately without clinical testing, but the FDA may request that the sponsor collect further
clinical data. If this occurs, the sponsor must still adhere to the regulations pertaining to
investigational devices (21 CFR 812) IRB review and informed consent regulations.

If the FDA determines that a new device is not substantially equivalent to a current device, then
safety and efficacy data must be collected under IRB approved clinical research. Once this data
is collected a Pre Market Approval (PMA) application can be submitted to the FDA to obtain

1
  FDA Device Advice guidance classifies Class III devices as having an unreasonable risk of illness or injury;
however, this definition does not coincide with the recent guidance. The term substantial risk was more appropriate
in this context.
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Mount Sinai School of Medicine (MSSM)
Program for the Protection of Human Subjects (PPHS) Policies & Procedures
Revised: 7/30/07
approval to market the device. The submission of a PMA application is the FDA process of
scientific and regulatory review to evaluate the safety and effectiveness of Class III medical
devices, and permit them to be marketed in the United States.

In order to collect the clinical data to support a PMA or 510(k) submission, an Investigational
Device Exemption (IDE) application must be submitted before studies are initiated unless the
device study meets IDE exemption requirements (see below). An approved Investigational
Device Exemption (IDE) allows an investigational device to be used in a clinical research study
to collect safety and effectiveness data on humans. If not exempt, the Sponsor must submit an
IDE to the FDA (for significant risk devices) or to the PPHS (non-significant risk devices).

Exemptions from IDE requirements
Under 21 CFR 812, the FDA allows for some device studies to be exempt from the IDE
requirements. As previously stated, those devices that are exempt are generally classified into
Class I or Class II categories. In determining if a device is exempt from the IDE regulations, the
device must fall into one of the following categories:
   1. a legally marketed device when used in accordance with its labeling
   2. a diagnostic device if it complies with the labeling requirements in §809.10(c) and if the
        testing:
                  is noninvasive;
                  does not require an invasive sampling procedure that presents significant
                    risk;
                  does not by design or intention introduce energy into a subject; and
                  is not used as a diagnostic procedure without confirmation by another
                    medically established diagnostic product or procedure;
   3. The device test must be limited to:
             consumer preference testing,
             testing of a modification, or
             testing of a combination of devices if the device(s) are legally marketed device(s)
                 and the testing is not for the purpose of determining safety or effectiveness and
                 does not put subjects at risk

If a device meets the criteria to be exempt from the IDE requirements, the IRB does not have to
decide whether the study poses a significant risk or non-significant risk, however, the IRB will
review the study in accordance with the requirements for IRB review and approval under Part 56
and the requirements for obtaining informed consent under Part 50. The Sponsor must provide
adequate justification to the IRB to support the determination of the exemption. For a list of
exempt devices go to http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpcd/315.cfm.

Policy
The IRB must review and approve protocols involving investigational devices.

Procedure
Material to be provided to IRB
Sponsors are responsible for making the initial determination about the potential risk that the
device presents. To help in the determination of the risk status of a device, the PI should submit
the following documentation to the IRB:
          Sponsor’s risk assessment of the device
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Mount Sinai School of Medicine (MSSM)
Program for the Protection of Human Subjects (PPHS) Policies & Procedures
Revised: 7/30/07
          Device description
          Reports of prior investigations with the device
          Proposed investigational plan (i.e. this includes background, specific aims, inclusion
           and exclusion criteria, etc)
          Participant selection criteria description
          Monitoring procedures
          Device Brochure
          Determinations to be made by other IRBs, if applicable
          FDA’s risk assessment of the devices risk, if applicable

Significant Risk/Non-Significant Risk Device Determination
IRB Responsibilities
When a device is being evaluated for safety and/or efficacy, the device is considered
investigational and is generally subject to the requirements of the IDE regulations (21 CFR 812).
Unless the FDA has already made a determination with a risk determination of the device (in
which case such documentation should be provided and their determination is final), or it meets
the requirements for exemption from the IDE regulations, the IRB must designate a risk
category as either a Significant Risk (SR) or Non-Significant Risk (NSR) for investigational
devices at a convened meeting.

The risk determination is based on the proposed use of a device in an investigation, not on the
device alone. The IRB will consider the potential harm a procedure could cause, as well as the
potential harm caused by the device. The IRB may consult with the FDA for its opinion at any
time.

Significant Risk Devices
Definition
A device that is determined to be a Significant Risk device is one that presents the potential for
serious risk to the health, safety, or welfare of a subject and is
         intended as an implant, and/or
         used in supporting or sustaining human life, and/or
         substantially important in either diagnosing, curing, mitigating or treating disease or in
            preventing impairment of human health.
Examples include sutures, cardiac pacemakers, hydrocephalus shunts, and orthopedic implants.

IRB Responsibilities
If the IRB determines that the research involves a SR device, the IRB must obtain evidence that
the Sponsor received an approved IDE from the FDA, unless it qualifies for an exemption from
IDE requirements (see IDE Exemption section). If an IDE has not already been obtained, the
IRB should notify the PI in writing that the IRB approval is pending receipt of an approved IDE
[21 CFR 812.30].

Investigator Responsibilities
The PI must provide the IRB with the IDE approval documentation, IDE exemption
documentation, evidence that 30 days have elapsed from submission of the IDE application to
the FDA, or other FDA correspondence.



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Mount Sinai School of Medicine (MSSM)
Program for the Protection of Human Subjects (PPHS) Policies & Procedures
Revised: 7/30/07
Furthermore, research involving the use of a SR device must be conducted in accordance with
the full requirements of the IDE regulations (21 CFR 812) as well as the Informed Consent (21
CFR 50) and IRB regulations (21 CFR 56). The investigator must maintain accurate and
complete records relating to the investigation under §812.140. These records include:

   1. all correspondence with another investigator, the IRB, the sponsor, a monitor, or FDA,
        including required reports
   2.   records of receipt, use, or disposition of the investigational device, that relate to the:
             type and quantity of device
             date of receipt
             batch number or code
             name of person that received, used, or disposed of each device
             why and how many units of the device have been returned to the sponsor,
                repaired, or otherwise disposed of
   3.   records of each subject's case history and exposure to the device which must include:
             signed and dated consent forms
             condition of each subject upon entering the study
             relevant previous medical history
             record of the exposure to the investigational device, including the date and time
                of each use and any other therapy
             observations of adverse device effects
             medical records (physician and nurse progress notes, hospital charts, etc.)
             results of all diagnostic tests
             case report forms
             any other supporting data
   4.   the protocol and documentation, including the date and the reason for each deviation
        from the protocol.
   5.   any other records that FDA requires to be maintained by regulation or by specific
        requirement for a category of investigation or a particular investigation
   6.   Research with an investigational device must be conducted in accordance with the
        MSSM policies to ensure that there is an adequate plan for device management,
        purchasing, billing, and cost recovery.

Non-Significant Risk Devices
Definition
A device would be classified as non-significant risk if it did not meet the criteria for a significant
risk device. Therefore, non-significant risk devices may NOT present the potential for serious
risk to the health, safety, or welfare of a subject AND may not be:
                 intended as an implant, and/or
                 used in supporting or sustaining human life, and/or
                 substantially important in either diagnosing, curing, mitigating or treating disease
                     or in preventing impairment of human health.
Examples include functional non-invasive electrical neuromuscular stimulators, wound
dressings, tongue depressors, etc.

IRB Responsibilities
The IRB will review the documentation provided by the Sponsor regarding the initial NSR
assessment. The IRB will consider the proposed use of the device as well as any protocol
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Mount Sinai School of Medicine (MSSM)
Program for the Protection of Human Subjects (PPHS) Policies & Procedures
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related procedures and tests, not just the device alone. If the IRB agrees that the device poses
"Non-Significant Risk" in the context of the research proposed, obtaining IDE approval from the
FDA is not necessary, and the research may begin when IRB approval occurs.

Some NSR device studies may qualify as “minimal risk” and may be reviewed through an
expedited review procedure (21 CFR 56.110). However, research on cleared/approved
marketed devices that significantly increases the risks or decreases the acceptability of the risks
associated with the use of the product, is not eligible for expedited review. The FDA considers
an investigation of a non-significant risk device to have an approved IDE when the IRB concurs
with the non-significant risk determination and approves the study.

Investigator Responsibilities
The Sponsor must provide an initial explanation to support its NSR determination. Research
involving the use of a NSR device must be conducted in accordance with the abbreviated
requirements of the FDA 21 CFR 812.2(b), IRB review and informed consent regulations.
Clinical investigators must maintain the records of each subject’s history and exposure to the
device under §812.140(a)(3)(i). Case histories should include case report forms and supporting
data, including signed and dated consent forms and medical records, including progress notes
of the physician, the individual’s hospital chart(s), and the nurses’ notes. Records must include
documents demonstrating informed consent and, for any use of a device without informed
consent, any written concurrence of a licensed physician and a brief description of the
circumstances justifying the failure to obtain informed consent. The history of each study
participant should have documentation that informed consent was obtained prior to participation
in the study. In addition, research with an investigational device (SR/NSR) must be conducted
in accordance with MSSM policies to ensure that there is an adequate plan for device
management, purchasing, billing, and cost recovery.

After the Determination of Device Study Risk
The IRB’s determination of significant risk or non-significant risk of a device as used in the
proposed study will be noted in IRB meeting minutes. The IRB minutes will also describe the
reasoning for its SR or NSR determination. The Investigator will be notified of this determination
in the investigator memo.

Once the final risk determination has been determined, the IRB must consider whether or not
the study should be approved. The IRB will assure that:
    1. risks to subjects are reasonable in relation to the anticipated benefits, the risks and
       benefits of the investigation should be compared to the risks and benefits of alternative
       devices and procedures,
    2. subject selection is equitable,
    3. informed consent materials and procedures meet the informed consent regulations and
       assure that:
        no claims should be made to state or imply, directly or indirectly, that the device is
           safe and effective for the purposes under investigation
        the consent should contain a statement that the device is investigational and not
           FDA approved
        a statement should be included that the FDA may have access to the participants
           medical records as they pertain to the study


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Mount Sinai School of Medicine (MSSM)
Program for the Protection of Human Subjects (PPHS) Policies & Procedures
Revised: 7/30/07
         the investigator must ensure that throughout the consenting process and study
          participation, the subject understands that the device is experimental and that its
          benefits for the condition are unproven
   4. provisions for monitoring the study are adequate and
   5. protecting the privacy of subjects is acceptable

Investigator Maintenance of Records
According to the FDA, investigators must maintain the required records (see “Investigator
Responsibilities” under Significant Risk devices) for a period of two years after the date the
investigation is completed or terminated, or when the records are no longer required to support
a PMA whichever date is later. Further, institutional requirements may apply; therefore,
relevant institutional resources should be consulted (MSSM Handbook for Research: Acquisition
and Storage of Data, HIPAA for Research).

An investigator may withdraw from the responsibility to maintain records for the time required by
transferring custody to another person who will accept responsibility for them. If an investigator
or sponsor transfers custody of the records to another person, FDA must be notified within 10
working days after the transfer occurs. The IRB should be notified through an Amendment
submission, for Instructions refer to the Personnel Changes guidance at
http://www.mssm.edu/PPHS/pdfs/personnel_changes.pdf.

Sponsors, IRBs, and investigators are required to permit authorized FDA employees reasonable
access at reasonable times to inspect and copy all records of an investigation. Upon notice,
FDA may inspect and copy records that identify subjects.

Special Cases for use of an unapproved device, or an approved device for an
unapproved indication
An unapproved medical device may normally only be used on human subjects through an
approved clinical study in which the subjects meet certain criteria and the device is only used in
accordance with the approved protocol by a clinical investigator participating in the clinical trial.
However, there may be circumstances under which a health care provider may wish to use an
unapproved device to save the life of a patient or to help a patient suffering from a serious
disease or condition for which no other alternative therapy exists. Patients/physicians faced with
these circumstances may have access to investigational devices under one of four main
mechanisms by which FDA may make an unapproved device available. These mechanisms
include:

       1.   Emergency Use
       2.   Compassionate Use
       3.   Treatment Use
       4.   Continued Access

Emergency Use
Under usual circumstances, the use of an investigational device in human subjects requires
prior approval of the IRB. Rarely, there are emergency circumstances where it is in the best
interest(s) of a patient for an investigational device to be used when IRB review and approval
have not yet been possible. The “emergency use provision” in the FDA regulations [21 CFR
56.104(c)] is an exemption from prior review and approval by the IRB. The exemption, which

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Mount Sinai School of Medicine (MSSM)
Program for the Protection of Human Subjects (PPHS) Policies & Procedures
Revised: 7/30/07
may not be used unless all of the conditions described in 21 CFR 56.102(d) exist (see below)
allows for ONE emergency use of a test article on ONE individual without prospective IRB
review at an institution.

Emergency use is defined as the use of an investigational device with a human subject in which:

      The subject has a disease or condition which is life-threatening (e.g., the likelihood of
       death is high) or severely debilitating (e.g., may cause irreversible morbidity, such as
       blindness, loss of limb, loss of hearing, paralysis or stroke);
      no generally acceptable alternative for treating the patient is available AND
      no IRB approved protocol exists for the manner in which the device needs to be used,
       the physician is not yet part of an existing clinical study, the patient in question is
       ineligible for participation in IRB-approved protocol(s) AND there is not sufficient time to
       obtain IRB or FDA approval.

The FDA expects the physician to determine whether these criteria have been met, to assess
the potential for benefits from the unapproved use of the device, and to have substantial reason
to believe that benefits will exist. If the physician determines that the patient’s circumstances
meet the criteria for the use of the device the physician must follow as many of the following
procedures as possible:

   1. If the physician is expecting an emergency use might be necessary, the physician
      should contact the PPHS staff, in order to get the regulatory process underway.
   2. The physician must notify the device Sponsor of the request for emergency use, and
      verify that the sponsor will make the device available for the PI’s use. If an IDE does
      not exist, the physician should notify FDA of the emergency use request, and provide
      FDA with a written summary of the conditions constituting the emergency, subject
      protection measures, and (afterward) results from the use. The physician can contact
      the CDRH Program Operation Staff at (301) 594-1190.
   3. The physician must obtain permission for emergency use of the investigational device in
      writing to his/her Chairperson or Division Chief. This letter must include a description of
      the patient's condition and an explanation as to why the test article is the only acceptable
      course of treatment the patient can receive.
   4. A written, independent assessment by an uninvolved physician must be obtained. In
      appropriate cases, the Dept or Division Chair could serve in this role.
   5. The physician must explain the situation to the patient or their legally authorized
      representative/health care proxy/surrogate and obtain informed consent for use of the
      device. The physician should use the institutional form “Permission Slip #3” (Form C-2-
      F-3 available at all nursing stations) to document this informed consent process. If the
      patient is unable to provide informed consent, see the section entitled “Emergency Use
      of an Investigational Device Without Informed Consent”.
   6. Upon receiving the written approval of the Department Chairperson or Division Chief, the
      physician/investigator must take this letter, along with Permission Slip #3 (standard
      clinical form available at all nursing stations throughout the hospital) to the Director of the
      Pharmacy, Annenberg Building, B2-12 (extension 212-241-2493) The director of the
      Pharmacy is the individual designated by the Institutional Review Board as being the
      institutional official authorized to approve emergency use requests. The Pharmacy will
      notify the Institutional Review Board on behalf of the physician of the request for
      emergency use of the device, within five (5) working days.
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Mount Sinai School of Medicine (MSSM)
Program for the Protection of Human Subjects (PPHS) Policies & Procedures
Revised: 7/30/07
   7. For emergency use of a test article at the Bronx VA Medical Center, VA policy M-3, Part
      1, Chapter 9.15(f)(2)(a) requires separate authorization from the Under Secretary for
      Health for patients outside a research protocol for each such emergency use of a test
      article without IRB review, contact the VA Research Compliance at (718) 584-9000
      extension #6014 to obtain the appropriate Emergency Use device forms. These forms
      must be filed with the Chief of Pharmacy Services.

When granted, "emergency use" will allow that physician/investigator to treat that one
patient for one course of treatment at the institution. Any other subsequent use can only
be conducted under an approved protocol. The IRB does not have the capacity to allow the
use of the device more then once for emergency use. FDA regulations require that any
subsequent use of the investigational product at an institution have prospective IRB review and
approval. An investigator who anticipates the need to use the device in other individuals in the
future at the institution should not delay submission to the IRB so as to create a situation where
prospective IRB review is impracticable prior to subsequent uses.

Furthermore, Federal regulations for the protection of human subjects do not permit research
activities to be started, even in emergencies, without prior IRB review and approval of a
research protocol and applicable consent forms. Thus, if a patient is treated via this emergency
use mechanism, then that patient, and any data derived from the treatment of that patient, may
not be used for research.


Emergency Use of an Investigational Device Without Informed Consent
Even for an emergency use, the investigator is required to obtain informed consent of the
subject or the subject's legally authorized representative. If, in the investigator's opinion,
immediate use of the test article is required to preserve the subject's life and it is not feasible to
obtain informed consent, special provisions for exception from informed consent requirements
must be met. The physician must certify in writing to the PPHS that all four of the following
specific conditions have been met:

   1. The subject has a disease or condition which is life-threatening (e.g., the likelihood of
      death is high) or severely debilitating (e.g., may cause irreversible morbidity, such as
      blindness, loss of limb, loss of hearing, paralysis or stroke);
   2. No alternative method of approved or generally recognized therapy is available that
      provides an equal or greater likelihood of saving the subject's life.
   3. Informed consent cannot be obtained because of an inability to communicate with, or
      obtain legally effective consent from, the subject;
   4. Time is not sufficient to obtain consent from the subject's legally authorized
      representative

This certification should be added to the request presented to the Dept/Division Chair as
described above in the section “Emergency Use”. All other steps delineated above in the
section “Emergency Use” (except Permission Slip #3) should be followed.

For more information on Emergency use of Devices go to
(http://www.fda.gov/oc/ohrt/irbs/devices.html#emergency).

Compassionate Use (or Single Patient/Small Group Access)
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Mount Sinai School of Medicine (MSSM)
Program for the Protection of Human Subjects (PPHS) Policies & Procedures
Revised: 7/30/07
The compassionate use provision allows access for patients who do not meet the requirements
for inclusion in the clinical investigation but for whom the treating physician believes the device
may provide a benefit in treating and/or diagnosing their disease or condition. This provision is
typically approved for individual patients but may be approved to treat a small group. The
Compassionate Use of a device is allowed only after a clinical trial has been initiated, if a patient
has a:

                 Serious disease or condition and
                 There is no alternative intervention available

FDA recognizes that there are circumstances in which an investigational device is the only
option available for a patient faced with a serious, albeit not life-threatening, disease or
condition. In these circumstances, FDA uses its regulatory discretion in determining whether
such use of an investigational device should occur.

The sponsor must agree with the Principal Investigator’s Compassionate Use of the device and
must receive FDA approval before the use occurs. Under these circumstances IRB
review/concurrence of the IRB Chair and informed consent is required.

Treatment Use
An approved IDE specifies the maximum number of clinical sites and the maximum number of
human subjects that may be enrolled in the study. During the course of the clinical trial, if the
data suggests that the device is effective, then the trial may be expanded to include additional
patients with life-threatening or serious diseases and the following conditions are met:

             There is no alternative intervention available AND
             The treatment use is being used under a controlled clinical trial AND
             The Sponsor is pursuing marketing approval

A device that is not approved for marketing may be under clinical investigation for a serious or
immediately life- threatening disease or condition in patients for whom no comparable or
satisfactory alternative device or other therapy is available. During the clinical trial or prior to
final action on the marketing application, it may be appropriate to use the device in the
treatment of patients not in the trial under the provisions of the treatment investigational device
exemptions (IDE) regulation. (§812.36)

The sponsor must agree with the Principal Investigator’s Treatment Use of the device and must
receive FDA approval before the use occurs. Under these circumstances IRB review and
informed consent is required.

Continued Access
Continued Access allows access to a device while a marketing application is being prepared
and reviewed and can be used to collect additional evidence of safety and effectiveness, as well
as to address new questions regarding the investigational device. The Continued Access may
be applied for after the completion of the clinical trial if there is:

                      A Public health need for the device and

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Mount Sinai School of Medicine (MSSM)
Program for the Protection of Human Subjects (PPHS) Policies & Procedures
Revised: 7/30/07
                 There is preliminary evidence that the device is likely to be effective and no
              significant safety concerns have been identified for the proposed indication.

The sponsor must agree with the Principal Investigator’s Continued Access Use of the device
and must receive FDA approval before the use occurs. Under these circumstances IRB review
and informed consent is required.

Humanitarian Use Device (HUD)/Humanitarian Device Exemption (HDE)
In some circumstances the FDA allows for some devices to be utilized as a Humanitarian Use
Device (HUD). A Humanitarian Use Device (HUD) is a device “intended to benefit patients in
the treatment and diagnosis of diseases or conditions that affect or is manifested in fewer than
4,000 individuals in the United States per year.” The HUD provision of provides an incentive for
the development of devices for use in the treatment or diagnosis of diseases affecting these
populations. After receiving this designation from the FDA, the sponsor can then submit a
Humanitarian Device Exemption (HDE) application to the FDA to allow the marketing of the
device in the United States. An HDE application is similar to a PMA application in that safety of
the device must be shown, but it does not require proof of efficacy like an IDE application. If the
FDA were to require efficacy data, given the relative rarity of the condition/disease, it would
block the progress of the device coming to market for many years. After the FDA approves the
HDE, the HUD is authorized for its labeled use, but even this non-research use requires local
IRB approval; since rigorous safety and efficacy data was not required prior to permitting it to be
used, the FDA, in effect, delegates the oversight of the use of the devices to local IRBs.

Requirements for use of an HUD at Mount Sinai and its affiliate institutions
Initial Review
The IRB must approve the use of an HUD and determine whether expedited continuing review
is appropriate, during the initial review by full-board review procedures. The IRB has the option
of granting approval on a case-by-case basis, or the IRB can grant approval for the indicated
uses for an entire year. The scope of the IRB approval should be documented in the IRB
minutes and communicated to the PI in the approval letter. IRB approval for the use of the
device should be forwarded to the holder of the HDE (sponsor) and current IRB approval must
be maintained for continuing use of the device.

The PI should report adverse events associated with the use of the device, modifications for the
use and patient population, etc. as per standard PPHS policies. It is imperative that any
changes in the status of the device as an HUD are communicated to the IRB in a timely manner
(e.g., the HDE is withdrawn by the FDA, or the device is cleared/approved for marketing either
for a separate indication or the same indication).

Please note that the use of the HUD only applies for individuals who are registered to use the
device. Each individual who would like to use the HUD must be associated with an IRB
approved application—therefore it would behoove departments to collaborate when filing such
applications, so that individuals who intend to be able to use the device will all be registered on
the same project. All personnel using the HUD must understand the obligations of using the
device.

Continuing Review
For continuing review, the IRB has the option of reviewing HUDs under expedited review. As
per FDA guidance:
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Mount Sinai School of Medicine (MSSM)
Program for the Protection of Human Subjects (PPHS) Policies & Procedures
Revised: 7/30/07
IRBs are responsible for initial as well as continuing review of the HUD. For initial review
of an HUD, IRBs are required to perform a full board review. For continuing review,
however, IRBs may use the expedited review procedures (section 56.110) unless the
IRB determines that full board review should be performed. The FDA believes that the
expedited review procedures are appropriate for continuing review since the initial
review would have been performed by the full board and use of a HUD within its
approved labeling does not constitute research.
http://www.fda.gov/cdrh/ode/guidance/1381.html

The determination of whether expedited continuing review is appropriate for a particular device
should be made at the time of initial full board review. Regardless of the initial determination, at
the time of the IRB renewal application, an expedited review is only appropriate if no substantive
modifications have been made regarding the use of the device and if no additional risks have
been identified. Expedited continuing review should be done by a board member with expertise
in the particular clinical area for which the device will be used, in conjunction with review by one
of the IRB chairs.

Investigator Responsibilities: Submission requirements for use of a non-research HUD
In order to have a HUD initially reviewed by the IRB, an application must be logged in at the
GCO office with 3 copies of documents given to the PPHS office. The PI should submit the
following documents:
     1. All required GCO forms
     2. Description of the device (from the sponsor)
     3. Copy of the HDE letter from the FDA authorizing use of the device
     4. Patient information booklet (from the sponsor)
     5. Humanitarian Use Device form
     6. PPHS form 4 (assurance page)
     7. Any other relevant documents regarding the device from the FDA or sponsor.
     8. A consent document is generally not needed nor does the PI need to request a waiver of
        informed consent. However, it is strongly encouraged that subjects be informed that the
        device has not been proven to be safe and effective and be provided with brief
        information on the device, in language that can be understood by individuals with no
        medical background. If the patient information booklet from the sponsor does not
        accomplish this mission, the IRB may determine that the PI should create a
        consent document to be used in conjunction with the patient information supplied
        by the sponsor.

For continuing review, the most recent versions of these documents should be submitted, with
original signatures. A progress report should be prepared as per the checklist for continuing
review applications. The progress report should include any updates from the FDA or sponsor
regarding the status of the HDE.

Use of HUD’s in research
If the device will be evaluated for research purposes (e.g., gather outcome data, or safety and
efficacy data to support a PMA), then a full PPHS application will be required, in addition to the
documents listed above. Informed consent and research HIPAA authorization must be obtained
from patients. Full-board review by the IRB is required for new applications.

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Mount Sinai School of Medicine (MSSM)
Program for the Protection of Human Subjects (PPHS) Policies & Procedures
Revised: 7/30/07
Emergency use of a HUD (device has not yet received IRB approval for the PI’s intended use)
IRB approval should be sought prior to use of the device under the indications in the HDE
application. However, in the case of an emergency situation in which IRB approval cannot be
granted prior to the use of the device, the HUD may be used. The device also may be used in
the case of an emergency situation for which off-label use of the HUD is sought. The FDA has
particular policies with regard to the use of unapproved devices under IDEs in emergency
situations, which should be followed for these devices (www.fda.gov/cdrh/ode/idepolcy.html, see
section on “Emergency Use of Unapproved Medical Devices). Before the device is used, if
possible, the physician should obtain:
     the IRB chairperson’s concurrence,
     informed consent from the patient or his/her legal representative,
     an independent assessment by an uninvolved physician.
     authorization from the HDE holder would be needed before the emergency use
        of the HUD, and
     after the emergency use occurs, the physician should submit a follow-up report
        on the patient’s condition and information regarding the patient protection
        measures to the HDE holder, who would then submit this report as an
        amendment to the HDE. http://www.fda.gov/cdrh/ode/guidance/1381.html

Non-emergency off-label use of HUDs (sometimes called “compassionate use”)
For “off-label” use of a HUD, the sponsor must agree with the Principal Investigator’s
Compassionate Use of the HUD device and must receive FDA approval before the use occurs,
unless it is an emergency situation (See Emergency Use of a HUD). Under these
circumstances IRB review/concurrence of the IRB Chair and informed consent is required.

For further information on HUD’s/HDE’s please go to
http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfHDE/HDEInformation.cfm.

Relevant Material
Investigational Device Form
MSSM PPHS Device Diagram
Humanitarian Use Device form

Reference Documents
21 CFR 50 and 56
21 CFR 50.24
21 CFR 812.2(b)
21 CFR 812.7
21 CFR 812, 814
FDA Tables for Expanded Access Mechanism

For FDA guidance and examples of NSR & SR devices go to
http://www.fda.gov/cdrh/d861.html.


Abbreviations
Pre Market Approval (PMA)
Investigational Device Exemption (IDE)
                                           Page 12 of 13

Mount Sinai School of Medicine (MSSM)
Program for the Protection of Human Subjects (PPHS) Policies & Procedures
Revised: 7/30/07
Significant Risk (SR)
Non-Significant Risk (NSR)
Humanitarian Use Device (HUD)
Program for the Protection of Human Subjects (PPHS)
Institutional Review Board (IRB)




                                           Page 13 of 13

Mount Sinai School of Medicine (MSSM)
Program for the Protection of Human Subjects (PPHS) Policies & Procedures
Revised: 7/30/07

								
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