21 CFR 312 Investigational New Drug Regulations
15-155 Describe the FDA'S definition of a "severely debilitating" disease? 21 CFR 312.81
The correct answer is: A disease or condition that may cause irreversible morbidity
15-155 What is FDA's definition of a "severely debilitating" disease?
The correct answer is: A disease or condition that may cause irreversible morbidity. 21 CFR 312.81
15-7: Define "contract research organization," according to the FDA's IND regulations?
The correct answer is: A person working with the sponsor as an independent contractor who assumes one or more of the obligations of the sponsor.
Define clinical hold?
The correct answer is: An order issued by the FDA to a sponsor to delay a clinical study.
15-55: What are the time requirement for filing IND safety reports with the FDA?
The correct answer is: As soon as possible and never later than fifteen calendar days after the sponsor's initial receipt of the information.
15-8: What types of products are generally subject to IND regulations?
The correct answer is: Investigational new drugs, biological drugs and biological products used in vitro for diagnostic purposes that are used in a clinical investigation.
15-10: What are labeling requirements for investigational drugs with respect to safety or effectiveness of the product?
The correct answer is: Label can bear no misleading statemetn and shall not represent that the drug is safe or effective for the purposes for which it is being investigated.
15-150 How must an investigator store the investigational drugs which are also controlled substances? 21 CFR 312.69
The correct answer is: Must be in a securely locked, substantially constructed cabinet or other enclosure with limited access to prevent theft or diversion of the substance into illegal channels of distribution.
15-120: Who has responsibility for ensuring that the IRB that complies with the requirements of 21CFR 56 will provide review and approval of an investigation?
The correct answer is: The investigator.
15-57: For purposes of filing an IND safety reports with the FDA, what is the definition of a "life-threatening event?"
The correct answer is: The patient was at immediate risk of death from the reaction as it occurred.
15-148 Name at least two types of information which an investigator must promptly report to the reviewing IRB?
15-148 The correct answer is: 1. All changes in the research. 2. All unanticipated problems involving risk to human subjects or others.
15-166 In general, FDA accepts foreign studies not conducted under an IND, provided what conditions are present?
15-166 The correct answer is: Provided the studies are: 1. Well designed. 2. Well conducted. 3. Performed by qualified investigator. 4. Conducted in accordance with ethical principles acceptable to the world community.
15-132 How long must the sponsor retain records of clinical investigations?
15-132 The correct answer is: Two years after a marketing application is approved for the drug, or if an application is not approved for the drug, until two years after shipment and delivery of the drug for investigational use is discontinued and the FDA has been notified.
15-133 The sponsors are required to reserve samples of any test article and reference standards used in bioequivalence or bioavailability studies, yet are not required to release these samples to the FDA. True or False?
15-133 The correct answer is: False. The sponsor is requested to release these samples to the FDA, upon their request.
15-134 What authority does FDA have regarding inspection of sponsor records?
15-134 The correct answer is: The FDA may have access to, inspect, copy, and verify any records and reports relating to a clinical investigation at reasonable times.
15-143 Maintenance of adequate and accurate case histories for study subjects includes documentation that informed consent was obtained prior to the subject's participation in the study. True or False?
15-143 The correct answer is: True.
15-144 A investigator is required to prepare and maintain adequate and accurate records and case histories for all study subjects. True or False?
15-144 The correct answer is: True.
15-145 For how many years must a investigator retain records of investigational drug supplies and study subject case records?
15-145 The correct answer is: Two years after NDA approval or, if an NDA is not approved, two years after the investigation has been discontinued and the FDS has been informed.
15-146 What types of reports is a investigator obligated to provide to the sponsor of a study?
15-146 The correct answer is: 1. Progress reports. 2. Safety reports. 3. A final report. 4. Financial disclosure reports.
15-147 What information must an investigator provide to the sponsor regarding his/her financial interests?
15-147 The correct answer is: Sufficient, accurate information to allow the sponsor to file required reports with the FDA, and any changes to their financial interests during or for one year after the close of the study.
If a clinical hold order is issued by the FDA for an ongoing study, what actions must the sponsor take?
Notify all investigators to stop recruitment of new subjects and to remove subjects from the investigational drug, unless specifically permitted to continue the ongoing patients, in the interest of safety.
15-156 What types of early consultation meetings are usually available for the INDs to evaluate life-threatening or severely debilitating illnesses?
The correct answer is: 1. A Pre-IND meeting to review animal data or study design, to discuss Phase 1 trial designs or data presentations in the IND. 2. An End-of Phase 1 meeting to discuss the design of Phase 2 trials. 21 CFR 312.82
Generally, sponsors may request FDA comment and advice for which components of an IND submission?
The correct answer is: 1. Adequacy of technical data to support an investigational plan. 2. Design of a clinical trial. 3. A determination of whether proposed investigations are likely to produce the data and information needed for an NDA.
15-108: What is the proper sequence of actions the sponsor should take when attempting to resolve an administrative or procedural dispute with the FDA>
The correct answer is: 1. Attempt to resolve the dispute with the reviewing division of CDER or CBER, beginning with the assigned Consumer Safety Officer (CSO). 2. If the dispute is not resolved via the CSO, seek resolution via an ombudsman.
15-109: What is the proper sequence of actions the sponsor should take when attempting to resolve a scientific or medical dispute with the FDA?
The correct answer is: 1. Discuss the matter directly with the responsible reviewing officials. 2. If unresolved, request a meeting with the reviewing officials and management representatives.
15-156 What are types of the early consultation meetings are usually available for IND's to evaluate life-threatening or severely debilitating illnesses? 21 CFR 312.82
The correct answer is: 1. Pre-IND meeting to review animal data or study design, used to discuss Phase 1 trial designs or data presentations in the IND. 2. End-of-Phase 1 meeting used to discuss the design of Phase 2 trials.
15-110: List at least three general responsibilities of the sponsors?
The correct answer is: 1. Select qualified investigators, providing them with information to properly conduct the trial. 2. Ensure proper monitoring. 3. Ensure the study is conducted in compliance with the protocol. 4. Maintain an effective IND. 5. Ensure FDA and investigators are provided full safety information.
Name at least two elements required to be reported for each individual study reported in an IND annual report
The correct answer is: 1. Study title, indentifier and purpose description of patient population and completion status. 2. Total number of subjects a) initially planned for inclusion, b) entered to date, c) who completed as planned, d dropped for any reason 3. Brief description of any interim or final analysis results, if available.
15-163 Import of investigational new drugs into the US is permissible provided the consignee meets one of three criteria. Please name the 3 criteria. 21 CFR 312.110
The correct answer is: 1. The US sponsor of the IND 2. A qualified investigator named in the IND 3. the domestic agent go the foreign sponsor, who is responsible for the control and distribution of the drug and is so identified in the IND.
15-117: Who must be specifically named on FDA Form 1572?
The correct answer is: 1. The investigator 2. The institution where the investigation will be conducted. 3.The clinical laboratory to be used in the study. 4.The IRB responsible for review and approval . 5. Any sub- investigators who will assist the investigator.
15-164 Name at least one of the two individuals who may submit a request for authorization to the FDA to export investigational drug outside of the United States. 21 CFR312.110
The correct answer is: 1. The person in the US who seeks to export the drug OR 2. An authorized agent of the country to which the drug is proposed to be shipped.
Name at least three grounds for FDA imposition of a clinical hold for a Phase 1, 2, or 3 investigation.
The correct answer is: 1.Subjects would be exposed to unreasonable and significant risk or illness or injury. 2. Unqualified investigators. 3. Inadequate Investigator Brochure. 4. Gender bias on subject eligibility.
15-154 Name the criteria for life-threatening diseases or conditions to which special IND regulations apply? 21 CFR 312.81
The correct answer is: Diseases or conditions: -Where the likelihood of death is higher unless the disease is interrupted - With the outcome where the end point of the clinical trial analysis is survival
15-9: What statement must the label of all investigational drugs have?
The correct answer is: "Caution: New Drug--Limited by Federal [or United States] law to investigational use".
15-121: What actions must the investigator take to make changes in a study protocol?
The correct answer is: 1. Inform the sponsor, request the change, and obtain a protocol amendment, if required. 2 Inform the IRB as needed, and request review and approval of the amendment. 3. Modify the consent form, if required, and obtain IRB approval. 4. Inform study patients of the pertinent changes, and obtain new informed consent, if applicable.
A revised copy of an Investigator Brochure in an IND annual report must be accompanied by what other additional information?
The correct answer is: A description of the revision(s).
15-61: If a sponsor evaluates an adverse experience and determines that is reportable as an IND safety report, but it was originally reported as such, how long does the sponsor have to report this event as an IND safety report?
The correct answer is: As soon as possible, but in no event later than fifteen calendar days after the determination is made.
15-60: When are sponsors required to file follow-up information for the IND safety reports?
The correct answer is: As soon as the relevant information is available
15-56: How soon must FDA be notified of a fatal or life-threatening adverse experience which is associated with use of a drug?
The correct answer is: By telephone or facsimile transmission, no later than seven calendar days after sponsor receipt of the information, followed by a written report no later than fifteen calendar days after the initial receipt of the information by the sponsor.
15-154 What is the criteria for life-threatening diseases or conditions to which special IND regulations apply for clinical trials?
The correct answer is: Conditions or diseases: -Where likelihood of death is high unless the disease is interrupted -with outcomes where the end point of the clinical trial analysis is survival. 21 CFR 312.81
15-151 If an investigator is disqualified by the FDA, what impact might that cause the sponsor? 21 CFR 312.70
The correct answer is: Data received from the disqualified investigators may be eliminated from the NDA consideration, and ultimately result in the FDA's failure to approve the NDA. Also, for approved drugs, data from the disqualified investigators could result in withdrawal of marketing approval by the FDA.
15-161 For what type of studies do the FDA officials intend to monitor study progress and evaluation to facilitate appropriate progress of the study trials! 21CFR 312.87
The correct answer is: Drugs intended to treat life-threatening or for severely debilitating illnesses.
15-161 For what type of studies does the FDA officials intend to monitor study progress and evaluation to facilitate appropriate progress of the trials?
The correct answer is: Drugs intended to treat life-threatening or severely debilitating illnesses. 21 CFR 312.87
15-62: If a sponsor submits an IND safety report, it is assumed by FDA that the drug caused or contributed to the event, unless it is specifically denied by the sponsor. True or False?
The correct answer is: FALSE Mere submission of a report under the IND safety report requirements does not reflect the conclusion, by either the sponsor or the FDA, that the drug caused or contributed to the reported event.
What is the FDA form for the investigator to use when filing a treatment IND.
The correct answer is: FDA FORM 1571
15-116: What FDA document must all investigators sign prior to participation in an investigation of a drug?
The correct answer is: FDA Form 1572
Clinical holds always apply to all clinical investigations under the IND.
The correct answer is: False A clinical hold order may apply to one or more investigations covered under an IND.
The FDA clinical holds apply to all sponsored clinical investigations under an IND, but do not apply to treatment INDs.
The correct answer is: False Clinic holds may apply to all research with a drug including a treatment IND.
Summary information for clinical trials activity within the past year is required in an IND annual report, while results of pre clinical studies are not
The correct answer is: False Pre clinical summary information for studies completed or concluded within the past year must be included in the IND annual report.
15-167 The FDA may disclose the existence of an IND, even though it was not previously been made public. True or False? 21 CFR 312.130
The correct answer is: False. FDA may not disclose that an IND exists if the fact has not been previously disclosed.
15-152 Once an investigator is disqualified by the FDA, he or she may never again receive investigational drug. True or False?
The correct answer is: False. The FDA may reinstate a disqualified investigator if the FDA Commissioner determines the investigator presents adequate assurances that they will work in full compliance with applicable regulations. 21 CFR 312.70 .
15-12: Can investigational drugs be commercially distributed or test-marketed by sponsors or investigators. T or F?
The correct answer is: False. Commercial distribution of investigational products is permitted.
15-11: Promotional claim is acceptable on investigational drug supply labeling, provided the claim was previously approved by the FDA. T or F?
The correct answer is: False. Promotional claims may not appear on the investigational drug supply labels.
15-126 Investigators are responsible for periodically requesting updates regarding new information received by a sponsor during the course of a clinical investigation. True or False? 21 CFR 312.55
The correct answer is: False: The sponsor is responsible to provide relevant new information about a drug, particularly with respect to adverse events and safe use via revisions to an Investigators Brochure, reprints of the published studies or reports or through other appropriate means
15-152 Once an investigator has been disqualified by the FDA, the investigator may never again receive investigational drug True or False? 21 CFR 312.70
The correct answer is: False: The FDA may reinstate a disqualified investigator if the FDA Commissioner determines that the investigator presents adequate assurances that they will work in full compliance with applicable regulations.
15-160 For what purposes might FDA undertake focused regulatory research? 21 CFR 312.86
The correct answer is: For evaluating critical rate-limiting aspects of the drug development process in facilitating the development of therapies to treat life-threatening or severely debilitating illnesses.
15-124: When the sponsor is conducting investigations under 21CFR 50.24, in emergency research conditions, what information must the sponsor promptly file with the FDA under the IND?
The correct answer is: Information received from the IRB concerning the public disclosure required by the regulation.
15- 149 In addition to granting permission to authorized FDA representative to have access to, copy, and verify study records, what information is an investigator required to divulge regarding each study subject?
The correct answer is: None, no other information. The investigator may withhold subject names unless the records of particular subjects require a more detailed study, or if there is reason to believe the records do not represent the actual cases, or results. 21 CFR 312.68
15-115: To whom may the sponsor provide investigational drugs?
The correct answer is: Only investigators participating in the clinical investigations under the IND.
15-118: According to the FDA Form 1572, what are an investigator's obligations for conducting the study and supervising those who assist the investigator in the conduct of the study?
The correct answer is: Personally conduct or supervise the investigation and ensure that all associates, colleagues, or employees involved in the investigation, are informed of the investigator's obligations.
15-153 Name the basic premise, relative to risk, of the IND regulations regarding drugs intended to treat life-threatening and severely debilitating disease? 21 CFR 312.80
The correct answer is: Physicians and patients alike are generally more willing to accept greater risks or side effects from drugs intended to treat severely debilitating or life-threatening illnesses.
15-142 Which records must be maintained by investigators for investigational drug supplies? 21 CFR 312.62
The correct answer is: Records of drug disposition that include dates, quantities, and use by study subjects.
15-142 What are records that must be maintained by investigators for investigational drug supplies?
The correct answer is: Records of drug disposition to include dates, quantities, and use by study subjects. 21 CFR 312.62
15-122: What is the sponsor's responsibility with respect to selecting monitors for a study?
The correct answer is: Select monitors who are qualified by training and experience to monitor the progress of the investigation.
15-111: If the sponsor desires to transfer some obligations to a contract research organization, what documentations must the sponsor prepare?
The correct answer is: Sponsors must describe, in writing, the specific responsibilities being transferred unless all responsibilities are being transferred, in which case a general statement will suffice. Any obligation not described in writing is deemed no to have been transferred.
15-13: Sponsors are prohibited from unduly prolonging clinical investigations, once adequate data has been generated for support of a marketing application. True or False?
The correct answer is: TRUE
15-15: Charging a reasonable amount for the investigational drugs under a treatment IND is permissible provided certain criteria are met and there is no commercialization or promotion involved. True or False?
The correct answer is: TRUE
15-1: IND regulations typically do not apply to investigations with lawfully marketed drugs which are being studied for purposes other than supporting a change in labeling or a change in advertising, so long as the study complies with IRB and consent regulations and it does not significantly increase risks or decrease acceptability of risks. True or False?
The correct answer is: TRUE
15-2: Some clinical investigations that involve an in vitro diagnostic biologic product may be exempt from the IND regulations if it used only to confirm a diagnosis made by another medically established diagnostic product or procedure. True or False?
The correct answer is: TRUE
15-3: Clinical research on blood grouping serum, reagent red blood cells and anti human globulin are generally exempt from FDA's IND regulation. True or False
The correct answer is: TRUE
15-4: Clinical investigations involving placebos may be exempt from IND regulations if the investigation does not otherwise require a submission of an IND application. True or False?
The correct answer is: TRUE
15-59: For marketed drugs, a sponsor is not required to file the IND safety report for events which are from non-clinical trial sources. True or False?
The correct answer is: TRUE
15-5: Use of marketed drug or biologic product for an unlabeled indication in the practice of medicine is not subject to IND regulations. True or False?
The correct answer is: TRUE
15-6: Researchers planning an investigation may contact the FDA to obtain guidance regarding the applicability of the IND regulations to a particular study. True or False?
The correct answer is: TRUE
15-71: "Treatment use" protocols are generally used once a drug's initial safety in Phase 2 trials has been demonstrated. True or False?
The correct answer is: TRUE
15-54: Who must be notified, via means of an IND safety report, of serious, unexpected adverse experiences that are associated with use of the drug?
The correct answer is: The FDA and all investigators conducting studies under the IND.
15-168 What additional information is available from FDA that applies to and supports interpretation of the FDA regulations? 21 CFR 312.145
The correct answer is: The FDA guidance documents which support interpretation of the regulations are available from both Center for Drug Evaluation and Research and the Center for Biologics Evaluation and Research.
Who must the sponsor notify if an effective IND is withdrawn by a sponsor for safety reasons?
The correct answer is: The FDA, all clinical investigations, and all reviewing IRBs; notification must include the reason for such withdrawal.
15-14: What is the FDA requirement for charging for investigational drugs under an IND.
The correct answer is: The charge for investigational drugs under an IND is not permitted without prior written approval from the FDA. Written explanation of why charges are necessary and not a normal cost of doing business is also required.
15-58: Who must approve modifications on the reporting format or frequency of the IND safety reports prior to a sponsor deviating from the regulations
The correct answer is: The director of the new drug review division of either the Center of Drug Evaluation and Research (CDER) or the Center for Biologics Evaluation and Research (CBER).
15-153 What is the basic premise, relative to risk, of the IND regulations regarding drugs which are intended to treat life-threatening and severely debilitating disease?
The correct answer is: The patients and physicians are generally more willing to accept greater risks or side effects from drugs intended to treat severely debilitating or life-threatening illnesses. 21 CFR 312.80
When FDA approves shipment of a drug for emergency use from a telephone request, what additional requirement typically is made of the sponsor
The correct answer is: The sponsor must make an appropriate IND submission as soon as practicable after receiving the approval.
15-150 How must investigators store investigational drugs which are also controlled substances?
The correct answer is: They must be securely locked, substantially constructed cabinet or other enclosure with limited access to prevent theft or diversion of the substance into illegal channels of distribution. 21 CFR 312.69
Unless the FDA notifies the sponsor that investigations in an IND are subject to a clinical hold, how soon may the sponsor begin a clinical investigation after filing the IND?
The correct answer is: Thirty days (30) after the FDA receives the IND submission.
15-112: When the sponsor transfers some or all its obligations to a CRO, the CRO is required to comply with all regulations designated as sponsor requirements for the transferred obligations.
The correct answer is: True
15-123: During an investigator selection process, sponsors are required to obtain a commitment from an investigator to provide financial disclosure statements before, during, and for one year after the completion of a study?
The correct answer is: True
15-158 A NDA is required for drugs intended to treat life-threatening diseases, however, special recognition of the medical risk/benefit must be given by FDA. True or False 21 CFR312.84
The correct answer is: True
15-159 Along with the approval of a drug for a life-threatening or severely debilitating disease, the FDA may request that the sponsor conduct Phase 4 studies to further evaluate the drug, TRUE OR FALSE 21 CFR 312.85
The correct answer is: True
15-162 All safeguards incorporated in FDA regulations regarding informed consent (21CFR 50), IRB review (21 CFR 56), IND (21 CFR 312), NDA (21 CFR 314) and Biologics (21 CFR 600) also apply to drugs intended to treat life-threatening or severely debilitating illnesses. True or False? 21 CFR 312.88
The correct answer is: True
An IND annual report should include the update description of the general investigational plan for the coming year.
The correct answer is: True
FDA Commissioner may deny requests for treatment-use of a drug for serious or life-threatening diseases if there is insufficient evidence to support its use.
The correct answer is: True
For a treatment INDs, the investigator is responsible for reporting safety information directly to the FDA.
The correct answer is: True
For serious or life-threatening diseases in patients for whom no alternative drug or comparable therapies are available may be evaluated outside of sponsor-planned clinical trials in a treatment protocol
The correct answer is: True
IF a licensed medical practitioner files a treatment IND with the FDA, the investigator becomes a sponsor-investigator, even though the sponsor may be supplying the drug
The correct answer is: True
The sponsor may withdraw an effective IND at anytime, without prejudice.
The correct answer is: True
15-158 Although a full NDA is required for drugs intended to treat life-threatening diseases, special recognition of the medical risk/benefit must also be given by the FDA. True or False?
The correct answer is: True. 21 CFR 312.84
15-159 Concurrent with approval of a drug for life-threatening or severely debilitating disease, the FDA may request the sponsor conduct Phase 4 studies to further evaluate the drug. True or False?
The correct answer is: True. 21 CFR 312.85
What does the phrase emergency use of an investigational drug imply, in FDA's IND regulations?
The correct answer is: Use of a drug in an emergency situation for which an IND application has not yet been filed.
15-63: What is the time frame in which the sponsor must file an IND annual report?
The correct answer is: Within 60 days of the anniversary date that the IND went into effect.