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NIH Investigator Manual for Human Subjects Research

Chapter 14 - FDA Regulated Research

Overview

Key Points

  • NIH investigators and non-NIH investigators conducting human subjects research involving drugs, biological products, medical devices, or nutritional products, must comply with all applicable FDA regulations.

  • An investigator is responsible for ensuring that an investigation is conducted according to the signed Investigator Statement (Form 1572), the investigational plan, and applicable regulations.

  • Sponsors for FDA regulated research have additional responsibilities such as reporting and monitoring requirements.
What is FDA regulated research?

FDA regulated research refers to human subjects research that involves the use of drugs, biological products, medical devices, or nutritional products (e.g., dietary supplements or foods) that are under the oversight of the Food and Drug Administration (FDA). (All NIH research is also subject to HHS regulations.)

How does the FDA define research within the context of human subjects research?
  • FDA has defined clinical investigation to be synonymous with research. Clinical investigation means "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."

  • Test article means any drug (including a biological product for human use), medical device for human use, human food additive, color additive, electronic product, or any other article subject to regulation under the act or under sections 351 and 354-360F of the Public Health Service Act.

  • Human subject means 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.

  • The FDA regulations that are specific to use of investigational devices defines "subject" as a human who participates in an investigation, either as an individual on whom or on whose specimen an investigational device is used or as a control. A subject may be in normal health or may have a medical condition or disease.
What is a sponsor with regard to FDA regulated research?
  • A sponsor for FDA-regulated research is defined as a person or other entity who initiates a clinical investigation, but who does not actually conduct the investigation. i.e., the test article is administered or dispensed to or used involving, a subject under the immediate direction of another individual. An entity other than an individual (e.g., a corporation or agency) that uses one or more of its own employees to conduct a clinical investigation that it has initiated is considered to be a sponsor, and the employees are considered to be investigators.

  • The sponsor may be an individual or pharmaceutical company, governmental agency, academic institution, private organization, or other organization. The sponsor does not actually conduct the investigation unless the sponsor is a sponsor-investigator. Sponsor-Investigator led studies are not permitted in the NIH IRP. However, investigators may have sponsor responsibilities when required by regulation.
What are my responsibilities if I am an investigator on an FDA regulated study?
  • Responsibilities include but are not limited to:
    • Ensuring that an investigation is conducted according to the signed Investigator Statement, the investigational plan, IRB approved protocol and applicable regulations.
    • Protecting the rights, safety, and welfare of subjects under the investigator's care.
    • The control of the test articles under investigation including documentation, maintenance, and tracking of the test article.
      • Some or all of the duties associated with this responsibility may be delegated to other appropriate individuals. For example, at the NIH CC, the CC Pharmacy Department is responsible for the receipt, storage, dispensing and disposition of all investigational drugs.
    • Obtaining the informed consent of each subject.
    • Comply with FDA required recordkeeping and retention.
    • Submit required reports to the sponsor in a timely manner (e.g., progress reports and safety reports).
    • Follow protocol mandated reporting requirement to the sponsor (e.g., reporting SAEs, Unanticipated Adverse Device Events, and other reportable events).
    • Investigators must make records available for FDA inspection. See Policy 500, Research Involving Drugs, Biological, and Nutritional Products, 21 CFR parts 56.115(b) and 312 for more information.
    • Specific responsibilities of clinical investigators are included in 21 part 50 and part 56.
    • More information regarding FDA requirements related to investigator responsibilities when conducting research with investigational drugs and biologics can be found here starting with section 312.60.
    • More information regarding FDA requirements related to investigator responsibilities when conducting research with investigational devices can be found at this section of Subpart E of 21 CFR 812.

  • For studies being conducted under an Investigational New Drug (IND) Application, some of the responsibilities of investigators are listed on the FDA Form 1572. See additional information below about the FDA form 1572, Statement of Investigator.

Research with FDA regulated drugs or biologics

How do I know if my study includes an FDA regulated drug or biologic?
What is an Investigational New Drug Application (IND)?
  • An Investigational New Drug Application (IND) is a request from a clinical study sponsor to obtain authorization from the Food and Drug Administration (FDA) to administer an investigational drug or biological product to humans. Clinical studies are often conducted to collect safety and effectiveness information for biologic and drug products.

  • Unless exempted, the sponsor for a clinical study must obtain authorization from FDA for conducting the study by submitting an IND Application. Such authorization must be secured prior to interstate shipment and administration of any new drug or biological product that is not the subject of an approved New Drug Application or Biologics Product License Application.

  • Information regarding IND applications for CBER-regulated (biologic) products can be found in this FDA document, Investigational New Drug Applications (INDs) for CBER-Regulated Products.

  • Please note: If the use of the test article is not exempt from the requirement for an IND, the IRBO will not further review the study, and research may not begin, until a valid IND is in effect. The PI is responsible for providing documentation to the IRB confirming that a valid IND is in effect. A valid IND is in effect:
    • Thirty days after the FDA receives the IND application, unless the FDA notifies the sponsor that the investigations described in the IND are subject to a clinical hold
      OR
    • An earlier notification by FDA that the clinical investigations conducted under the IND may begin

  • Investigators should provide documentation from the FDA verifying the IND number and indicating the study is safe to proceed (e.g., the FDA letter assigning the IND number and safe to proceed letter). If the safe to proceed letter has not been received, the IRB will accept documentation from the sponsor indicating the FDA's confirmation that the study may proceed.

  • The PI is also responsible for providing the IRB a copy of the Investigator Brochure (IB) or package insert for any test articles at time of Initial Review and is responsible for reviewing and providing the IB with any updates that occur. This is important for evaluating for any new risks to research subjects.
    • If no IB exists for an investigational drug, the investigator must include in the protocol all relevant preclinical and clinical safety and efficacy data to support the proposed use of the test article in the research.

  • For additional information, see NIH Human Research Protection Program (HRPP) Policy 500 which refers to Research Involving Drugs, Biological, and Nutritional Products.
What if my study is FDA regulated but I think my study should be considered IND Exempt?
  • There are categories of clinical investigations specified in the FDA regulations that are exempt from the IND requirements. If all the criteria under these categories are not met, then the study must be conducted under an IND.

  • Note that your study is still FDA regulated even if it is IND Exempt.

  • For detailed information and discussion of the IND Exempt criteria, please refer to section IV the FDA Guidance Investigational New Drug Applications (INDs)— Determining Whether Human Research Studies Can Be Conducted Without an IND. In summary, regarding the relevant FDA regulations, a clinical investigation of a marketed drug is exempt from the IND requirements if all of the criteria for an exemption are met:
    • The drug product is lawfully marketed in the United States.
    • The investigation is not intended to be reported to FDA as a well-controlled study in support of a new indication and there is no intent to use it to support any other significant change in the labeling of the drug.
    • In the case of a prescription drug, the investigation is not intended to support a significant change in the advertising for the drug.
    • The investigation does not involve a route of administration, dose, patient population, or other factor that significantly increases the risk (or decreases the acceptability of the risk) associated with the use of the drug product.
    • The investigation is conducted in compliance with the requirements for review by an IRB (21 CFR part 56) and with the requirements for informed consent (21 CFR 50).
    • The investigation is conducted in compliance with the requirement that the investigation is not intended to promote or commercialize the drug product.
What information must I provide to the IRB if I think use of the study drug or biologic is IND Exempt?
  • When the research involves the clinical investigation of a test article you must provide written justification in the protocol for why the test article is exempt from the requirement for an IDE. (See the criteria in the preceding question.) This information should be provided to the IRB as a part of the Initial Review Submission.

  • If the Office of IRB Operations (IRBO) does not concur with the investigator that the test article is exempt, the IRBO may require the investigator to submit to the FDA for a formal determination prior to further review of the study. The FDA determination as to whether the test article is exempt or requires an IND is final.

  • If you seek guidance from the FDA to make these determinations, they will provide you an outcome letter that you will include as a part of the Initial Review Submission.
What is the FDA Form 1572 and why is it important?
  • Form FDA 1572 is the Statement of Investigator that is collected by the sponsor for studies being conducted under IND. It is an agreement signed by the investigator to provide certain information to the sponsor and assure that they will comply with FDA regulations related to the conduct of a clinical investigation of an investigational drug or biologic.

  • Form FDA 1572 is important because in signing the form, the investigator affirms that they are qualified to conduct the clinical investigation, that they commit to follow pertinent FDA regulations, and the investigator confirms they are aware of their obligations.

  • Examples of obligations that the investigator agrees to by signing the 1572 include, but are not limited to:
    • Conduct the study(ies) in accordance with the relevant, current protocol(s) and only make changes in a protocol after notifying the sponsor, except when necessary to protect the safety, rights, or welfare of subjects
    • Personally conduct or supervise the described investigation(s)
    • Ensure that the FDA requirements relating to obtaining informed consent and IRB review and approval are met
    • Report to the sponsor adverse experiences that occur in the course of the investigation(s)
    • Read and understand the information in the investigator's brochure, including the potential risks and side effects of the drug
    • Ensure that all associates, colleagues, and employees assisting in the conduct of the study(ies) are informed about their obligations in meeting the above commitments
    • Maintain adequate and accurate records in accordance with relevant federal regulations and make those records available for inspection as required by FDA
    • Promptly report to the IRB all changes in the research activity and all unanticipated problems involving risks to human subjects or other
    • Not make any changes in the research without IRB approval, except where necessary to eliminate apparent immediate hazards to human subjects

  • For more details refer to the Information Sheet Guidance For Sponsors, Clinical Investigators, and IRBs: Frequently Asked Questions Statement of Investigator (Form FDA 1572).
As the investigator, what FDA-specific reports are required when my protocol is conducted under an IND?

Direct communication with the FDA is typically initiated and the responsibility of the sponsor of the study. As the site investigator, the following reports should be submitted to the sponsor to provide them the information they need to submit the required reports to the FDA:

  • Investigator Annual Progress Reports: You should provide regular updates regarding the progress of the trial to the sponsor of the drug who is responsible for collecting and evaluating the results obtained. The sponsor is required to submit annual reports to FDA on the progress of the clinical investigation, and they may require additional information from you around the time of this submission and ask you to submit an annual progress report. The contents of this report are dictated by the sponsor. For more information, see FDA's webpage: IND Application Reporting: Annual Reports.

  • Safety or SAE Reports: The required timeframe for the submission of these event reports events should be outlined in the protocol but is often 24 hours from the time of the investigator is notified of the event. The sponsor will have their own deadline to determine if these events meet the criteria for required reporting to the FDA. They may require additional information to be submitted after the initial report to complete their evaluation and submission. Events that need to be reported to the sponsor include:
    • Serious adverse events (SAEs), whether or not considered drug related, including those listed in the protocol or investigator brochure along with an assessment of whether there is a reasonable possibility that the drug caused the event.
    • The FDA requires that all serious events be reported to the sponsor regardless of the attribution by the investigator since the sponsor has access to the complete set of aggregated safety data that allows them to do a thorough investigation of any serious adverse reactions.
    • There may be non-serious events that are events of special interest that may also need to be reported to the sponsor expeditiously. The timetable for reporting these events should be specified in the protocol.
    • For more information, visit the FDA website: IND Application Reporting: Safety Reports

  • Investigator Final Report: The sponsor is required to submit a final report to the FDA after completing an investigation, so the sponsor may ask you to provide them with an adequate investigator final report shortly after completion of the investigation at your site. The content of this report is dictated by the sponsor.
If I am reporting an event to the sponsor, does the event also need to be reported to the IRB?
  • It will depend on the event. The reporting requirements for both sponsor and the IRB should be spelled out in the protocol. There may be times when events occur that need to be reported to the sponsor but not to the IRB.

  • The most common source of confusion is related to the reporting of Serious Adverse Events (SAEs) or Serious Suspected Adverse Reactions (SUSARs) and Unanticipated Problems (UPs). For example, SAEs will require reporting to the sponsor, but the SAE may not meet criteria for reporting to the IRB (e.g., the SAE is unrelated to the research and, as such, is not a UP.) These terms are not interchangeable, and the definitions of each should be reviewed at the time of reporting to make sure the event is reported to the appropriate entity. See Policy 801, Reporting Research Events for additional information.

  • See the following for additional information regarding reporting safety information:
What are my responsibilities for maintaining records when my FDA regulated research protocol involves drugs?

As the investigator, you are responsible for ensuring recordkeeping and record retention requirements are met as per 21CFR 312.57 and NIH Manual Chapter 1743, Managing Federal Records.

  • Disposition of drug: Maintain adequate records of the disposition of the drug, including dates, quantity, and use by participants. If the investigation is terminated, suspended, discontinued, or completed, the investigator should return the unused supplies of the drug to the sponsor, or otherwise provide for disposition of the unused supplies of the drug under 21CFR 312.59. Some or all of the duties associated with this responsibility may be delegated to other appropriate individuals. For example, at the NIH CC, the CC Pharmacy Department is responsible for the receipt, storage, dispensing and disposition of all investigational drugs.

  • Case histories: It is your responsibility to prepare and maintain adequate and accurate case histories that record all observations and other data pertinent to the investigation on each individual administered the investigational drug or employed as a control in the investigation. Case histories include the case report forms and supporting data including, for example, signed and dated consent forms and medical records including progress notes of the physician, the individual's hospital chart(s), and the nurses' notes. The case history for each individual should document that informed consent was obtained prior to participation in the study.

  • Length of Record Retention: Investigators and Sponsors are required to retain the records and reports after the trial is closed for the longest of the following intervals:
    • NIH Requirements: At least 3 years as required by the NIH Manual Chapter 1743-Managing Federal Records.
    • FDA Requirements:
      • Two years after a marketing application is approved for the drug.
      • If an application is not approved for the drug, records must be maintained for 2 years after shipment and delivery of the drug for investigational use is discontinued and FDA has been notified.
    • Data from withdrawn subjects:
      • When a participant withdraws from a study conducted under an IND, the data collected on the participant to the point of withdrawal remains part of the study database and may not be removed. 
      • You may not continue to access the participant's medical record or other confidential records for additional research purposes unless the participant has provided consent to do so.

Research with FDA regulated devices

What is a medical device?
  • In its Information Sheet Guidance For IRBs, Clinical Investigators, and Sponsors: Frequently Asked Questions About Medical Devices, FDA describes medical devices as an instrument, apparatus, implement, machine, contrivance, implant, in vitro reagent, or other similar or related article, including any component, part, or accessory, which is:
    • Recognized in the official National Formulary, or the United States Pharmacopeia, or any supplement to them
    • Intended for use in the diagnosis of disease or other conditions, or in the cure, mitigation, treatment, or prevention of disease, in man or other animals, or
    • Intended to affect the structure or any function of the body of man or other animals, and which does not achieve its primary intended purposes through chemical action within or on the body of man or other animals and which is not dependent upon being metabolized for the achievement of its primary intended purposes (21 U.S.C. 321(h))

  • Medical devices range from simple (e.g., tongue depressors) to highly complex programmable implanted devices (e.g., pacemakers). Additionally, medical devices include in vitro diagnostic (IVD) products, such as reagents, test kits, and blood glucose meters. Certain energy electronic products that have a medical use or make medical claims are also considered medical devices. Examples of these include diagnostic ultrasound products, x-ray machines and medical lasers.
How do I know if my study includes an FDA regulated investigational device?
  • Investigational devices are medical devices that are the object of a clinical investigation.

  • All clinical investigations of devices must have an approved Investigational Device Exemption (IDE) or be exempt from the IDE regulations.

  • Please refer to the following to determine step by step if your study uses a medical device that is regulated by the FDA: FDA information sheet How to Determine if Your Product is a Medical Device.
What does the term IDE mean?

IDE refers to the regulations under 21 CFR 812. An approved IDE means that the IRB (for nonsignificant risk devices) or the FDA (for significant risk devices) has approved the sponsor's study application and all the requirements under 21 CFR 812 are met. A list of relevant IDE Definitions and Acronyms is available on the FDA website.

If my study includes an investigational device, what criteria need to be met to make use of the device in my study exempt from the Investigational Device Exemption (IDE) regulations?
  • Some clinical investigations of the device are exempt from the IDE requirements in 21 CFR 812 and are described in §812.2(c) of the IDE regulations. For the full list, please see FDA webpage describing the IDE Approval Process (specifically the section related to IDE Exempt Investigations.)

  • Human subjects research studies that entail clinical investigation of a device are exempt from the IDE regulations if they include:
    • Legally marketed devices when used in accordance with FDA labeling
    • Diagnostic devices that comply with the FDA 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
      • is not used as a diagnostic procedure without confirmation by another medically established diagnostic product or procedure
    • Consumer preference testing, testing of a modification, or testing of a combination of devices if the devices are legally marketed devices AND if the testing is not for the purpose of determining safety or effectiveness and does not put subjects at risk
What information must I provide to the IRB if I think my device is IDE Exempt?
  • When the research involves the clinical investigation of an investigational device, you must provide written justification in the protocol for why the device is exempt from the requirement for an IDE. (See the preceding question for information about studies that may be exempt.) This information should be provided to the IRB as a part of the Initial Review Submission.

  • If the Office of IRB Operations (IRBO) does not concur with the investigator that the device is exempt, the IRBO may require the investigator to submit to the FDA for a formal determination prior to further review of the study. The FDA determination as to whether the device is exempt or requires an IDE is final.

  • If you seek guidance from the FDA to make these determinations, they will provide you an outcome letter that you will include as a part of the Initial Review Submission.
If my study includes an investigational device, when does my device fall under IDE regulations?
  • If you are studying a medical device that is the object of a clinical investigation and it has not been determined to be exempt from the IDE regulations, your protocol is subject to the IDE regulations at 21 CFR 812.

  • An investigational device exemption (IDE) allows an investigational device to be used in a clinical study in order to collect safety and effectiveness data. Investigational use also includes clinical evaluation of certain modifications or new intended uses of legally marketed devices.

  • An approved IDE permits a device to be shipped lawfully for the purpose of conducting investigations of the device without complying with other requirements of the Food, Drug, and Cosmetic Act that would apply to devices in commercial distribution.

  • Investigations covered under the IDE regulation are subject to differing levels of regulatory control depending upon the level of risk. Devices used under IDE fall into two levels of risk:
    • Significant Risk (SR) Device is an investigational device that
      1. is intended as an implant and presents a potential for serious risk to the health, safety, or welfare of a subject.
      2. is for use in supporting or sustaining human life and represents a potential for serious risk to the health, safety, or welfare of a subject.
      3. is for a use of substantial importance in diagnosing, curing, mitigating, or treating disease or otherwise preventing impairment of human health and presents a potential for serious risk to the health, safety, or welfare of a subject.
        or
      4. otherwise presents a potential for serious risk to a subject.
      • Examples of SR devices include sutures, Electroconvulsive Therapy (ECT) devices, cardiac pacemakers, replacement heart valves, cochlear implants, biliary stents, plasmapheresis systems hydrocephalus shunts, endometrial ablation systems, extended wear contact lenses, and orthopedic implants. See the following FDA information sheet for additional examples of SR devices: Significant Risk and Nonsignificant Risk Medical Device Studies
      • Investigational devices that meet the definition of significant risk, and that do not qualify as exempt, must have FDA and IRB approval. The sponsor must submit an IDE application to FDA and obtain approval prior to the PI's submission of the protocol for initial review by the NIH IRB.
    • Non-Significant Risk (NSR) Device: NSR devices are devices that are not IND Exempt and that do not pose a significant risk to the human subjects. They are not subject to full IDE requirements and do not require that an IDE application be submitted to the FDA. However, the determination does require confirmation by the IRB at a full board meeting.

  • Sponsors are responsible for making the initial device risk determination. The PI must include this initial determination and the sponsor's explanation for why the device does not pose a significant risk in the protocol.

  • The FDA is also available to help the sponsor, clinical investigator, and IRB in making the NSR determination, but no formal IDE application needs to be submitted (unless the FDA subsequently concludes the use of the device is considered SR).

  • Examples of medical devices that the FDA considers nonsignificant risk devices include most daily-wear contact lenses and lens solutions, dental filling material, EEG recording devices, MRI devices within FDA parameters, and urological ("Foley") catheters for short term use.

  • See the following FDA information sheet for additional examples of SR and NSR devices: Significant Risk and Nonsignificant Risk Medical Device Studies.

  • For more information see the FDA Webpage IDE Approval Process. Also see NIH HRPP Policy 501, Research Involving FDA Regulated Devices.


What type of device information is required for my protocol?

The following flow chart provides information on what is needed in the protocol related to use of an investigational device:

flowchart diagram representing decision tree

As the investigator, what FDA specific reports are required when my protocol includes an IDE?

Direct communication with the FDA is typically initiated and the responsibility of the sponsor of the study. As the site investigator, the following reports should be submitted to sponsor to provide them the information they need to submit the required reports to the FDA:

  • Unanticipated adverse device effects (UADE): The investigator must submit to the sponsor and the reviewing IRB a report of any unanticipated adverse device effect as soon as possible but no later than 10 working days after the investigator first learns of the UADE.

  • Withdrawal of IRB approval: The investigator must report to the sponsor a withdrawal of approval of the reviewing IRB within 5 working days.

  • Annual Progress Reports: The investigator must submit progress reports to the sponsor at regular intervals but no less than on a yearly basis. The contents of this report are dictated by the sponsor.

  • Deviations from the investigational plan: The investigator must notify the sponsor and the reviewing IRB of any deviation from the investigational plan to protect the life or physical well-being of a subject in an emergency. The notice must be provided as soon as possible but no later than 5 working days after the emergency occurred. If it is not an emergency, prior approval from the sponsor is required for changes in or deviations from the investigational plan. If the change or deviation may affect the scientific soundness of the investigational plan or the rights, safety or welfare of the subject, IRB approval must be obtained and, for SR investigations, the sponsor must obtain FDA approval by submitting an IDE supplement.

  • Failure to obtain informed consent: If an investigator uses a device without obtaining informed consent, the investigator must report the use to the sponsor and to the reviewing IRB within 5 working days after the use occurs.

  • Final report: The investigator must submit a final report to the sponsor within 3 months after termination or completion of the investigation.

  • Additional information can be found on the FDA webpage that addresses IDE Reports.
What are my responsibilities for maintaining records when my FDA regulated research protocol involves devices under IDE regulations (SR and NSR Devices)?

As the Investigator, you must keep accurate, complete and current records as specified in 21 CFR 812.140. These records include:

  • All protocol related correspondence with other investigators, IRB, sponsor, monitors, or the FDA.

  • Records of receipt, use or disposition of a device that include:
    • The type and quantity of the device, the dates of its receipt, and the batch number or code mark.
    • The names of all persons who 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:
    • Case report forms and supporting data including, for example, signed and dated consent forms and medical records including, for example, progress notes of the physician, the participant's hospital chart(s), and the nurses' notes.
    • Documents evidencing informed consent and, for any use of a device by the investigator 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 case history for each participant should document that informed consent was obtained prior to participation in the study.
    • All relevant observations, including records concerning adverse device effects (whether anticipated or unanticipated), information and data on the condition of each participant upon entering, and during the course of, the investigation, including information about relevant previous medical history and the results of all diagnostic tests.
    • A record of the exposure of each participant to the investigational device, including the date and time of each use.

  • The protocol and documentation (date and 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 investigations or a particular investigation.

  • For further information visit the FDA webpage IDE Records.

Expanded Access

What is Expanded Access and is this an option for patients who are not eligible for my trial?
  • Expanded Access is a potential pathway for a patient with an immediately life-threatening condition or serious disease or condition to gain access to an investigational medical product (drug, biologic, or medical device) for treatment outside of clinical trials (e.g., when patient is not eligible to enroll in a clinical trial) when no comparable or satisfactory alternative therapy options are available. This is also sometimes referred to as "compassionate use".

  • The PI must obtain FDA approval prior to use of test article under the FDA expanded access regulations. If the test article is a drug or biologic under IND, a Letter of Authorization must be obtained from the sponsor to cross reference the IND.

  • Expanded access use of a drug, biologic or medical device is not research. NIH Investigators may not perform research interventions or collect or analyze data for research purposes under an expanded access protocol.

  • Informed consent must be obtained from the subject or legally authorized representative (LAR), unless the requirements at 21 CFR 50.23(a) have been met.

  • Expanded access use of a test article must be conducted in accordance with applicable federal regulations.
What information must be documented in order for a patient to be eligible for expanded access use of a test article?
  • In order for a patient to be eligible for expanded use, the NIH Principal Investigator (PI) must determine and document (e.g., in the medical record, submission to the FDA, etc.) that the following criteria are met: 
    • Patient(s) must have a serious or immediately life-threatening disease or condition, and there is no comparable or satisfactory alternative therapy to diagnose, monitor, or treat the disease or condition;
    • The potential patient benefit justifies the potential risks of the treatment, and the potential risks are not unreasonable in the context of the disease or condition to be treated;
      and
    • The expanded use of the investigational test article for the requested treatment will not interfere with the initiation, conduct, or completion of clinical investigations that could support marketing approval of the product.

  • To be enrolled on an NIH expanded access protocol, a subject must already be enrolled on an NIH research protocol.
Do expanded access protocols require prospective IRB review and approval?
  • For expanded access protocols, prospective IRB review and approval must be obtained, except in certain cases of individual patient use of investigational drugs or biologics as noted below.

  • A physician submitting a new individual patient expanded access IND may request a waiver from the FDA regarding full IRB review when the physician obtains concurrence by the IRB Chair before treatment use begins. This option is available only for single patient non-emergency and single patient emergency use.
If I am conducting an expanded access protocol, do I need to submit reports to FDA or the IRB?
  • Reports that must be submitted to FDA include:
    • Follow-up and progress reports
    • Initial and follow-up safety reports
    • Annual Reports (for INDs) and semi-annual reports (for IDEs) and
    • Final report at the completion of treatment

  • Reporting to the IRB:
    • Submit Continuing Review application for expanded access protocols that will exceed a 12-month period, except in cases of emergency use.
    • Submit reportable events as per Policy 801, Reporting Research Events.
    • Notify the IRB when treatment is complete.
Where can I get more information about Expanded Access?


Chapter 15 - International Research