5.1 – Determining Whether FDA Regulations Apply5.2 – IRB ...



-205740762000LifeBridge Health Drug, Device and Biologic Studies PolicyTABLE OF CONTENTS Section Page NumbersPurpose2Scope2Definitions2Policy2 Procedures5.1 – Determining Whether FDA Regulations Apply5.2 – IRB Review5.3 – Principal Investigator Responsibilities5.4 – Emergency Use of a Test Article5.5 – Expanded Access/Compassionate Use of Investigational Drugs and Devices223679PurposeThe purpose of this Policy is to describe requirements and procedures for research that is subject to regulations of the Food and Drug Administration (FDA).ScopEThis policy applies to all Human Subject Research subject to FDA regulations for which the LBH IRB serves as the IRB of Record. DefinitionsAdverse event means any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug-related. Emergency Use means the use of an investigational product with a human subject in a “life-threatening” or “severely debilitating” situation in which no standard acceptable treatment is available and in which there is not sufficient time to obtain IRB approval.Independent Physician means a physician not otherwise participating in the patient’s care. Life-threatening means diseases or conditions where the likelihood of death is high unless the course of the disease is interrupted, and diseases or conditions with potentially fatal outcomes, where the end-point of clinical trial analysis is survival. The criteria for life-threatening do not require the condition to be immediately life-threatening or to immediately result in death. Rather the patient must be in a life-threatening situation requiring intervention before review at a convened meeting of the IRB is feasible.Severely Debilitating means conditions that cause major irreversible morbidity. Examples of severely debilitating conditions include blindness, loss of arm, leg, hand or foot, loss of hearing, paralysis or stroke.Unanticipated Adverse Device Effect is any serious effect on health or safety, any life-threatening problem, or death caused by, or associated with a device, if that effect, problem or death was not previously identified in nature, severity or degree of incidence in the investigational plan or application, or any other unanticipated serious problem associated with a device that relates to the rights, safety or welfare of subjects. PolicyThe LBH IRB and investigators will comply with applicable FDA laws and regulations in reviewing and conducting research involving drugs, devices, and biologics.ProceduresDetermining Whether FDA Regulations ApplyThe LBH Department of Research will determine which FDA regulations, if any, apply to a research study during pre-review of the IRB application materials provided by the Principal Investigator (in the absence of specific information from the FDA). The assessment may require obtaining additional information from the Principal Investigator, the sponsor, and/or the FDA. Issues to be considered include the following: Does the activity meet the FDA’s definition of “clinical investigation”? FDA defines “clinical investigation” as any experiment that involves a test article and one or more human subjects, and that either must meet the requirements for prior submission to the FDA or the results of which are intended to be later submitted to, or held for inspection by, the FDA as part of an application for a research or marketing permit. The terms?“research”, “clinical research”, “clinical study”, “study”,?and?“clinical investigation”?are deemed to be synonymous by the FDA.Does the activity involve the use of human subjects, as defined by the FDA? FDA defines “human subject” as an individual who is or becomes a participant in research, either as a recipient of the test article or as a control. A subject may be either a healthy individual or a patient.Is the research exempt from IRB review, as defined by the FDA (21 CFR 56.104)? Exempt research includes: Emergency use of a test article, provided that such emergency use is reported to the IRB within 5 working days; andTaste and food quality evaluations and consumer acceptance studies, under specified conditions. Is the activity considered investigational drug research that is governed by 21 CFR 312?The Principal Investigator will be asked whether an IND is required and the basis for that determination via IRBNet, and LBH Department of Research will ask the Principal Investigator for additional information if the assessment suggests that the Principal Investigator’s conclusion may be inaccurate. Is the activity considered investigational device research that is governed by 21 CFR 812?The Principal Investigator will be asked whether an IDE is required and the basis for that determination via IRBNet. The LBH Department of Research will ask the Principal Investigator for additional information if the assessment suggests that the Principal Investigator’s conclusion may be inaccurate. Does the activity involve the use of a Humanitarian Use Device (HUD) that is governed by 21 CFR 814? If yes, follow LBH Humanitarian Use Device Policy. If the FDA has stated that the research involving the specific use of the item is subject to its regulations, relevant FDA regulations will be applied in the IRB review. IRB ReviewPre-review. LBH Department of Research conducts a pre-review of the application materials provided by the Principal Investigator (a) to determine whether the FDA regulations apply to the research, following the procedures described above in Section 5.1 and, if yes, which FDA regulations apply, and (b) to determine whether the research requires review by a full convened IRB, or is eligible for expedited review pursuant to LBH Expedited Review Policy. Note: The existence of, or apparent need for, an IND or IDE disqualifies the study for expedited review. Determination of whether an IND or IDE is required.LBH Principal Investigators who are sponsor-investigators and who believe they need an IND or IDE are strongly encouraged to submit their IND and IDE application to the FDA before or at the same time as submitting the IRB application to the IRB, to reduce delays in study start-up time. The IRB asks the Principal Investigator whether an IND or IDE is required and the basis for that determination. If the IRB believes that the study requires an IND or IDE but the Principal Investigator and/or sponsor do not, the IRB has the authority to require the Principal Investigator and/or sponsor to provide or obtain confirmation from the FDA that an IND or IDE is not required. Device risk assessment. For studies involving an investigational device, the convened IRB must determine whether the use of the device involves “significant risk” or “non-significant risk”. The risk determination is specific to the use of the device in the proposed study. The Principal Investigator is responsible for providing the IRB with any information relevant to this determination, including a copy of the FDA’s determination (if one has been made). The sponsor is required by FDA regulations to provide the IRB with its risk assessment and rationale. If the sponsor believes that the use of the device is “non-significant risk”, then an IDE application is not required by the FDA and there will be no FDA determination of risk. If the sponsor has submitted an IDE application to the FDA, then approval of the IDE by the FDA indicates that the FDA considers the device to be significant risk. When the FDA has already made a risk determination, if the determination was “significant risk”, the FDA’s decision is final and the IRB’s determination must concur; and if the determination was “non-significant risk”, the IRB may choose to concur with the FDA or it may override the FDA’s determination with a “significant risk” determination. The IRB’s risk assessment decision is based on some or all of the following: Risk determination already made for the study.Risk determination for other uses of the device. Information in the database maintained by the applicable device division of the FDA. Sponsor’s risk assessment and rationale. Principal Investigator’s risk assessment and rationale. Nature and description of the device, including its inherent risks. Description of procedures and tests that are required because of the device. (For example, the IRB may consider the potential harm caused by a surgical procedure necessary to implant a device as well as the potential harm caused by the device itself). Subject population and selection criteria. (The use of a device may have more potential for harm in certain subject populations than in others – for example, subject populations comprised of frail elderly individuals with significant health issues).Reports of any prior investigations conducted with the device. Review of the device and study by other IRBs. The IRB’s determination is communicated as follows: To the Principal Investigator. The IRB is required to communicate the determination to the Principal Investigator and in the IRB meeting minutes. The minutes should describe the IRB’s reason for its risk determination and may also include the documentation used to establish the IDE status for the study. For a significant risk determination, such documentation may include, for example, a copy of the IDE approval or conditional approval letter from FDA. For a non-significant risk determination, the documentation may include FDA's NSR determination where the agency has made the determination. FDA will issue an NSR letter upon written request.To the sponsor. A significant risk decision must be communicated to the sponsor. This is accomplished by Department of Research staff writing a memo to the sponsor. To the FDA. The sponsor is responsible for communicating a significant risk decision to the FDA within 5 days after learning of the decision. The risk determination affects the requirement for an IDE. If the IRB determines that the device is “significant risk”, the study must have an IDE application approved by the FDA and documented for the IRB. Consent form elements. The IRB confirms that the following are included in the consent process and forms: FDA review. A statement indicating that the FDA may review subject medical records and research records which identify the subjects. Clinical trial registration. For applicable clinical trials which must be registered with the database, the following statement informing subjects that the clinical trial has been registered with the database, and that some research data will be submitted to the database: “A description of this clinical trial will be available on? required by U.S. Law. This Web site will not include information that can identify you. At most, the Web site will include a summary of the results. You can search this Web site at any time.” The FDA regulations (21 CFR 50.25(c)) require that this exact statement be used, without revision. Risks. The IRB reviews the Investigator Brochure to ensure that the risk information in the consent form conforms to the information in the Brochure. For device studies, the IRB includes a consideration of the risk of implants, the possible need to remove them, and how removal would be managed and funded. Waiver of documentation of consent. The FDA allows a waiver of documentation of consent, but in more limited circumstances than is allowed by the HHS (“Common Rule”) regulations. See LBH Informed Consent Policy.Principal Investigator Responsibilities in Drug and Device StudiesIn addition to the general responsibilities of Principal Investigators set out in other LBH policies, the Principal Investigator conducting IND or IDE research is responsible for complying with all other applicable requirements set out in 21 CFR Part 312 (for investigational drug studies) and 21 CFR Part 812 (for investigational device studies). These responsibilities include but are not limited to the following reporting obligations: Adverse drug event reports (21 CFR 312.64, 21 CFR 312.66)The Principal Investigator must report to the sponsor any Adverse Event (AE) that may be reasonably regarded as caused by or possibly caused by the drug. The Principal Investigator must report promptly to the IRB all Unanticipated Problems that, in the judgement of the PI or study sponsor, are more likely than not to meet the definition of an UPIRSO, including AEs that are Unanticipated Problems. In general, an AE observed during the conduct of a study should be considered an Unanticipated Problem and reported to IRB if it is unexpected, serious and could have implications for the conduct of the study. An individual AE occurrence ordinarily does not meet these criteria unless it is (i) a serious, unexpected event that is uncommon and strongly associated with drug exposure; or (ii) a serious, unexpected event that is not commonly associated with drug exposure but is uncommon in the study population. Reportable AEs also may include those that are addressed in the investigator’s brochure, protocol or informed consent documents but (i) that occur at a specificity or severity that is inconsistent with prior observations; or (ii) for which the rate of occurrence in the study represents a clinically significant increase in the expected rate of occurrence. For multi-center studies, the Principal Investigator may rely on the sponsor’s assessment and provide to the IRB a report of the Unanticipated Problem prepared by the sponsor. Unanticipated adverse device effects (UADEs) (21 CFR 812.3(s)) The Principal Investigator must report UADEs to the sponsor and IRB as soon as possible and in no event later than 10 working days after (s)he first learns of the event. The sponsor must investigate UADEs and report results to the FDA, IRB and participating investigators within 10 working days after receiving notice of the UADE. 5.4Emergency Use of a Test ArticleIndividual Patient Emergency Use.Physicians must contact the Department of Research to determine whether a full board meeting can be convened before use of the investigational drug, device, or biologic is necessary. Expedited review procedures may not be used to grant approval of an emergency use.In situations where time does not allow for review by the convened IRB, a one-time Emergency Use of an investigational product is allowed without prior IRB approval, provided that such Emergency Use is reported to the IRB within 5 working days. The report must contain the following information:The name of the physician responsible for administering the investigational product;The name of the investigational product;The initials of the patient who received the investigational product;The date the investigational product was administered;A summary of the conditions that constituted the emergency use (i.e., life-threatening or severely debilitating situation in which no standard acceptable treatment is available); The outcome;A copy of the informed consent document used or a signed certification as noted below under “Informed Consent”; andA signed attestation by the physician indicating that the situation under which the investigational product was used met the definition of “Emergency Use.”Any subsequent use of the same investigational product by the same physician must have prior IRB approval.Under FDA regulations, the Emergency Use of a test article, other than a medical device, is a clinical investigation, the patient is a research subject, and the FDA may require data from an Emergency Use to be reported in a marketing permit. DHHS regulations do not permit data obtained from patients to be classified as human subject research, nor permit the outcome of such care to be included in any report of a research activity subject to DHHS regulations.Some manufacturers may request LBH Department of Research acknowledgement prior to emergently shipping the investigational drug, biologic, or device. If there is not time to convene a meeting of the full board to review the Emergency Use, the IRB chair or designee will issue a letter indicating that the IRB is aware of the proposed use under the FDA regulations at 21 CFR 56.014(c).Specific approvals by and reporting to the FDA may also be required, including requirements to obtain verbal authorization by a reviewing FDA official for use of an investigational drug and to submit an expanded access IND or protocol within 15 working days of FDA’s authorization of the use. For FDA contact information for emergency use of drugs and biologics, see . For FDA contact information for emergency use of medical devices, see . Informed Consent. Even in Emergency Use situations, informed consent must be obtained whenever feasible. If time does not allow for a convened IRB meeting, the consent form, whenever possible, should be reviewed by Department of Research staff. If there is no time to seek Department of Research staff review, the physician is responsible for ensuring that the appropriate elements of informed consent are included. (See Informed Consent Policy.)An exception from the requirement to obtain informed consent is allowed only when both the physician responsible for the Emergency Use and an Independent Physician, before use of the investigational article, certify in writing that all of the following exist:The patient is confronted by a Life-threatening or Severely Debilitating situation necessitating the use of the investigational rmed consent cannot be obtained because of an inability to communicate with, or obtain legally effective consent from, the patient.Time is not sufficient to obtain consent from the patient’s legal representative.No alternative method of approved or generally recognized therapy is available that provides an equal or greater likelihood of saving the patient’s life.If, in the physician’s opinion, immediate use of the investigational product is required to preserve the patient’s life, and if time is not sufficient to obtain an independent physician’s determination, the physician responsible for the Emergency Use may alone make the certification prior to administering the investigational product. The situation must then be reviewed and evaluated by a physician who is not involved in the patient’s care, and this individual should certify that the above-listed conditions were met.The certifications noted above must be submitted to the Department of Research along with the Emergency Use report within 5 working days from the use of the test article.Review of Emergency Use Report. The IRB chair will review the Emergency Use report and certifications regarding exception to obtain informed consent. The IRB will be notified of the Emergency Use at a convened IRB meeting. The meeting minutes will document IRB notification.5.5Expanded Access/Compassionate Use of Investigational Drugs and DevicesInvestigational Drugs.Except for emergency expanded access use when there is not sufficient time to secure prospective IRB review (see Section 5.3 above) or FDA waiver of IRB review requirements (see Section 5.5(a)(ii) below), an investigator treating a patient with an investigational drug under expanded access (also known as compassionate use) is responsible for obtaining IRB review and approval consistent with FDA regulations before treatment with the investigational drug may begin, regardless of whether the expanded access protocol is submitted in a new IND or as an amendment to an existing IND. In the case of emergency expanded access use, FDA authorization is still required (21 CFR § 312.310(d)), but it is not necessary to wait for IRB approval to begin treatment. The FDA may waive the requirement for IRB review of an individual patient expanded access IND if FDA concludes that such a waiver is appropriate provided that the physician obtains concurrence by the IRB chairperson or another designated IRB member before treatment use begins.FDA instructions for expanded access use of investigational drugs are available at . Investigational Devices. Except for emergency expanded access use of an investigational device for a patient when there is not sufficient time to secure prospective IRB review (see Section 5.4 above), a physician treating a patient who has a life-threatening or serious disease or condition and for which there exists no generally acceptable alternative treatment with an investigational device under expanded access (also known as compassionate use) is responsible for obtaining IRB approval and satisfying all other FDA requirements (including obtaining FDA approval) before treatment with the investigational device may begin. If the Department of Research determines, in discussion with the IRB chair, that there is not sufficient time to obtain convened IRB review, the expanded access use may proceed upon concurrence of the IRB chair (as permitted by FDA guidance). Any problems associated with expanded access use of an investigational device should be reported to the IRB as soon as possible. In addition, the physician should submit to the IRB a copy of the report of patient outcome provided to the FDA.FDA instructions for expanded access use of investigational devices are available at . ................
................

In order to avoid copyright disputes, this page is only a partial summary.

Google Online Preview   Download