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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. Page 1 of 13 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 Page 2 of 13 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. Page 3 of 13 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, 2. 3. 4. 5. 6. including required reports 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 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 the protocol and documentation, including the date and the reason for each deviation from the protocol. any other records that FDA requires to be maintained by regulation or by specific requirement for a category of investigation or a particular investigation 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 Page 4 of 13 Mount Sinai School of Medicine (MSSM) Program for the Protection of Human Subjects (PPHS) Policies & Procedures Revised: 7/30/07 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 Page 5 of 13 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. 2. 3. 4. Emergency Use Compassionate Use Treatment Use 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 Page 6 of 13 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-2F-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. Page 7 of 13 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) Page 8 of 13 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 Page 9 of 13 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: Page 10 of 13 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. Page 11 of 13 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