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Human subject research involving drugs, including supplements, devices, and biologics must be in compliance with relevant Food and Drug Administration (FDA) and Department of Health and Human Services (DHHS) laws and regulations. Investigators planning, designing and implementing research with these products must be aware of and adhere to all applicable federal and state regulations, as well as institutional policy and procedure.

The purpose of this policy is to ensure that studies conducted by �鶹Ů�� (�鶹Ů��) investigators comply with FDA and DHHS regulations and good clinical practice (GCP) to ensure the protection and welfare of human subjects participating in research.

Prior to initiation of research involving a drug, device, or biologic, the Principal Investigator or sponsor must assess whether they must obtain an Investigational New Drug (IND) Application, Investigational Device Exemption (IDE), a Humanitarian Use Device Exemption (HDE), or a Biologics License Application (BLA) from the FDA. If not, a justification and documentation that use of the product meets the requirements for an exemption from IND or BLA requirements or the device is exempt from an IDE under 21 CFR812.2 (c) must be provided upon submission for IRB review.

All ongoing and proposed clinical trials conducted by �鶹Ů�� faculty that use investigational a drug, device, or biologic must be fully compliant with all FDA and DHHS regulations. The Institutional Review Board of record will review all clinical research protocols involving a drug, device, or biologic for evidence of compliance with the applicable laws and regulations. Initial review of research involving the use of FDA regulated products, not specifically stated in , will undergo full committee review.

As of September 27, 2018, �鶹Ů�� does not engage in FDA regulated investigator initiated clinical trials or in Phase 0 or Phase 1 industry sponsored clinical trials.

510(K) Device: Devices that are substantially equivalent to other devices that are legally on the market are called 510(K) devices and can be marketed without clinical testing.

Biologic: A biologic (e.g. biological product) includes any virus, therapeutic serum, toxin, antitoxin or similar product applicable to the prevention, treatment or cure of human diseases or injuries. The term includes a biological product that is used in vitro for diagnostic purposes. (21 CFR 600.3)

Clinical Investigation: Any experiment in which a drug is administered to, dispensed to, or used involving one or more human subjects. An experiment is any use of a drug except for the use of a marketed drug in the course of medical practice (21 CFR 312.3). Clinical investigation of a previously untested drug is generally divided into three phases (21CFR312.21).

Phase 1. Phase 1 includes the initial introduction of an investigational new drug into humans. Phase 1 studies are typically closely monitored and may be conducted in patients or normal volunteer subjects. These studies are designed to determine the metabolism and pharmacologic actions of the drug in humans, the side effects associated with increasing doses, and, if possible, to gain early evidence on effectiveness. The total number of subjects and patients included in Phase 1 studies varies with the drug but is generally in the range of 20 to 80. Phase 1 studies also include studies of drug metabolism, structure-activity relationships, and mechanism of action in humans, as well as studies in which investigational drugs are used as research tools to explore biological phenomena or disease processes.

Phase 2. Phase 2 includes the controlled clinical studies conducted to evaluate the effectiveness of the drug for a particular indication or indications in patients with the disease or condition under study and to determine the common short-term side effects and risks associated with the drug. Phase 2 studies are typically well controlled, closely monitored, and conducted in a relatively small number of patients, usually involving no more than several hundred subjects.

Phase 3. Phase 3 studies are expanded controlled and uncontrolled trials. They are performed after preliminary evidence suggesting effectiveness of the drug has been obtained and are intended to gather the additional information about effectiveness and safety that is needed to evaluate the overall benefit-risk relationship of the drug and to provide an adequate basis for physician labeling. Phase 3 studies usually include from several hundred to several thousand subjects.

Custom Device: a device that meets the following criteria:

1. Deviates from devices generally available or from an applicable performance standard or pre-market approval requirement to comply with the order of an individual physician or dentist;
2. Is not generally available to, or generally used by, other physicians or dentists;
3. Is not generally available in finished form for purchase or for dispensing upon prescription;
4. Is not offered for commercial distribution through labeling or advertising; and
5. Is intended for use by an individual patient named in the order of a physician or dentist, and is to be made in a specific form for that patient, or is intended to meet the special needs of the physician or dentist in the course of professional practice.

Device: An instrument, apparatus, implement, machine, contrivance, implant, in vitro reagent, or other similar or related article, including any component, part or accessory, which is intended for use in the diagnosis, cure, treatment or prevention of disease. A device does not achieve its intended purpose through chemical action in the body and is not dependent upon being metabolized to achieve its purpose (21 CFR 812.3).

Drug: As defined by the Food, Drug and Cosmetic Act, drugs are articles (other than food) intended for the use in the diagnosis, cure, mitigation, treatment, or prevention of disease in man or other animals, or to affect the structure or any function of the body in man or other animals.

Humanitarian Use Device: A Humanitarian Use Device (HUD) is a device that is intended to benefit patients by treating or diagnosing a disease or condition that affects fewer than 4,000 individuals in the United States per year, and where the effort of development generally does not yield a profit for manufacturers. An HDE allows a HUD to be used without the results of scientifically valid clinical investigation demonstrating that the device is effective for its intended purpose, but it must be used under certain conditions (21 CFR 814 Subpart H).

Implant: A device that is placed into a surgically or naturally formed cavity of the human body if it is intended to remain there for a period of 30 days or more. FDA may, in order to protect public health, determine that devices placed in subjects for shorter periods are also “implants”.

Investigation: A clinical investigation or research involving one or more subjects to determine the safety or effectiveness of a device.

Investigational Device: A device, including a “transitional device,” that is the object of an investigation.

Investigational Device Exemption (IDE): An approved IDE means that the FDA has approved the sponsor’s IDE application for a clinical investigation involving a significant risk device.

Investigational New Drug (IND): A drug or biologic that does not have an approved marketing application and is used in a clinical investigation. This includes marketed drugs being studied at new doses, routes of administration or indications that do not appear in the product label (21 CFR 312.2).

Investigator: An individual who actually conducts a clinical investigation; under whose immediate direction the test article is administered or dispensed to, or used involving, a subject, or, in the event of an investigation conducted by a team of individuals, is the responsible leader of that team.

Monitor: When used as a noun, means an individual designated by a sponsor or contract research organization to oversee the progress of an investigation. The monitor may be an employee of a sponsor or a consultant to the sponsor, or an employee of or consultant to a contract research organization. Monitor, when used as a verb, means to oversee an investigation (21 CFR 812.3(j)).

Noninvasive: When applied to a diagnostic device or procedure, means one that does not by design or intention: (1) Penetrate or pierce the skin or mucous membranes of the body, the ocular cavity, or the urethra, or (2) enter the ear beyond the external auditory canal, the nose beyond the nares, the mouth beyond the pharynx, the anal canal beyond the rectum, or the vagina beyond the cervical os. For purposes of this part, blood sampling that involves simple venipuncture is considered noninvasive, and the use of surplus samples of body fluids or tissues that are left over from samples taken for noninvestigational purposes is also considered noninvasive (21 CFR 812.3(k)).

Non-Significant Risk Device (NSRD): An investigational device that does not meet the definition of a significant risk device. In some cases, these devices may be qualified for an IDE. Sponsors are responsible for making the initial risk determination and presenting it to the IRB. FDA is also available to help the sponsor, clinical investigator, and IRB in making the risk determination.

Significant Risk Device (SRD) 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 purported or represented to be for a use in supporting or sustaining human life and presents 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 the health, safety, or welfare of a subject.

Sponsor: Entity that takes responsibility for and initiates a clinical investigation. 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. A person other than an individual that uses one or more of its own employees to conduct an investigation that it has initiated is a sponsor, not a sponsor-investigator, and the employees are investigators.

Sponsor-Investigator: An individual who both initiates and conducts an investigation, and under whose immediate direction the investigational drug is administered or dispensed. In some instances, clinical investigations subject to FDA regulation are initiated by an individual rather than a company or corporate entity.

Subject (Participant): A human who participates in an investigation, either as a recipient of the investigational new drug or as a control. A subject may be a healthy human or a patient with a disease.

In addition to the Responsibilities of Investigators per ; ; and :

The Principal Investigator will be responsible for:

• Not initiating the clinical investigation before obtaining all necessary approvals, specifically the IRB approval and if needed, FDA approval.
• The PI and study team must complete Good Clinical Practices (GCP) training via CITI or another �鶹Ů�� approved GCP training mechanism, prior to initiating a clinical investigation of a medical device.
• Conducting the study in accordance with the protocol, and making changes only after they obtain approval from the IRB of record, except when necessary to protect the safety, rights or welfare of participants.
• Complying with all regulatory requirements regarding the protocol.
• Personally conducting and supervising the investigation.
• Informing any potential participant when a test article is being used for investigational purposes
• Ensuring that the requirements of informed consent are met, including conveying in an understandable manner the information in the investigator’s brochure, drug, device, or biologic label, including the potential risks and side effects.
• Ensuring that the protocol has been reviewed and approved by the IRB of record before any participants are enrolled in the study.
• Reporting to the sponsor and IRB adverse events that occur in the course of the investigation.
• Ensuring that the investigation is conducted according to the signed statement, protocol and related investigational plan, and applicable laws and regulations.
• Protecting the rights, safety and welfare of the participants in the clinical study, including the confidentiality requirements.
• Maintaining control of the investigational drugs, devices, or biologics.
• Preparing and maintaining adequate documentation.

In addition to the Responsibilities of Sponsors per ; ; and :

The Study Sponsor will be responsible for:

• Ensuring that the proposed clinical investigation has appropriate FDA approvals prior to study initiation.
• Assuming all other functions of sponsor as outlined in applicable FDA regulations.

In addition to the provisions of and :

The IRB of record will be responsible for:

• Reviewing any human subject clinical investigation involving a new drug, device, or biologic for compliance with the FDA laws and regulations.
• Unless FDA has already made a risk determination for the device study, reviewing the sponsor’s SR or NSR determination for every investigational medical device study it reviews and modifying the determination if it disagrees with the sponsor.

Drugs or Biologics

The PI must initiate the required IND or BLA documentation prior to submitting an IRB application package to the IRB of record. Researchers are strongly encouraged to contact FDA to obtain further guidance prior to the submission of an IND (or BLA) application, especially if they are uncertain about the proposed study’s regulatory status.

The PI must submit, as part of the IRB application package, a copy of the FDA IND/BLA paperwork (or exemption) letter. In addition, if the sponsor doesn’t supply a standard protocol and consent template, the PI must complete Form 109, “Greater than Minimal Risk Protocol” and consent form(s) using the Form 101, “Biomedical Research Consent”.

The PI must await FDA, IRB, and Sponsored Programs approval before initiating any data collection for a clinical trial of an investigational new drug/biologic at �鶹Ů��.

Devices

The sponsor or sponsor-investigator must make an initial assessment of their study’s FDA IDE status and, if applicable, initiate the required IDE documentation prior to submitting an IRB application package. Researchers are strongly encouraged to contact FDA to obtain further guidance prior to the submission of an IDE application, especially if they are uncertain about the proposed study’s regulatory status.

The PI must submit, as part of the IRB application package, evidence of an IDE approval number, or documentation of non-significant risk or exemption status. In addition, if the sponsor doesn’t supply a standard protocol and consent template, the PI must complete Form 109, “Greater than Minimal Risk Protocol” and consent form(s) using the Form 101, “Biomedical Research Consent”.

The PI must await FDA, IRB, and Sponsored Programs approval before initiating any data collection for a clinical trial of an investigational medical device at �鶹Ů��.

Policy Renewal Date: As needed

45 CFR 46

21 CFR 50

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