IRB Manual
       7.2 Drugs, Devices & Biologics for Human Use that have not received marketing approval and investigational use of marketed drugs
 

The IRB must review all research involving the administration of drugs (approved drugs and experimental drugs) or the use of medical devices. In addition, the IRB is responsible for reviewing treatment ("compassionate") and emergency uses of investigational drugs and medical devices.


 7.2.1 IND's and IDE's
   

Regulations issued by the Food and Drug Administration govern clinical investigations that support applications for research or marketing permits for products regulated by the F.D.A., including drugs for human use, medical devices for human use and biological products for human use. Consent forms for all studies regulated by the F.D.A. must specify that the F.D.A. may inspect the research records.

Drugs and biologics which are not approved for marketing and that enter interstate commerce may only be administered to a patient/subject under a Notice of Claimed Exemption for A New Drug (IND) filed with the F.D.A.

An investigational device requires an approved Investigational Device Exemption (IDE) application unless the investigation is exempt from IDE regulation. Exempt investigations include investigations of devices which F.D.A. has approved for marketing, certain diagnostic devices, and custom devices. A non-significant risk device investigation is considered to have an IDE, without submission of an application to F.D.A., if IRB approval has been obtained and certain other abbreviated IDE requirements have been met.

Drugs and devices requiring IND's or IDE's may be administered to patients/subjects (treatment and/or research) under the following conditions:

  1. The sponsor (usually the drug company but may also be the investigator) has complied with the applicable requirements under the Federal Food, Drug and Cosmetic Act.
  2. Approval of the use of the investigational drug or device use has been obtained from the IRB, RFMH and from the appropriate commissioner.
  3. Informed consent of each patient or his/her authorized representative has been obtained.
  4. An up-to-date list of all patients involved in the project is maintained by the facility director.
  5. Investigational drugs shall be used only under the direct supervision of the authorized principal investigator or treating physician.
  6. OMH facilities only:

    1. The proposed use or treatment procedure has received specific written approval from the Commissioner's Designee (research use) or the Chief Medical Officer (treatment use). At NYSPI this authority has been delegated to the Director;
    2. Use of the investigational drug has been approved by the facility's Pharmacy and Therapeutics Committee.
    3. Investigational drug products shall be stored and distributed by the facility pharmacy to individual patients when approved for use. Perpetual inventories of investigational drug products on hand and a record of disbursements shall be maintained.
    4. Investigational drug dispensing shall be documented using the Pharmacon computer system. Investigational drugs shall be so noted in the computer formulary by the designation "I" for drug type. Users should be reminded that the primary drug interaction file will not screen investigational drugs for drug - drug interactions.

   
When an investigational new drug is to be administered by a nurse or another practitioner not directly involved in the study, the following information should be provided to that person (in writing): (1) pharmacology (particularly adverse effects); (2) method of dose preparation and administration; (3) precautions to be taken; (4) authorized prescriber(s); (5) patient monitoring guidelines; and (6) any other material pertinent to the safe and proper use of the drug.


 7.2.2 Clinical Investigations of Marketed Drugs
   

Clinical investigations of a drug product that is lawfully marketed in the United States (i.e. approved for marketing by the FDA) do not require an IND if all of the following apply:
  1. The investigation is not intended to be reported to the FDA as a well-controlled study in support of a new indication for use nor intended to be used to support any other significant change in the labeling for the drug;
  2. If the drug that is undergoing investigation is lawfully marketed as a prescription drug product, the investigation is not intended to support a significant change in the advertising for the product;
  3. The investigation does not involve a route of administration or dosage level or use in a patient population or other factor that significantly increases the risks (or decreases the acceptability of the risks) associated with the use of the drug product;
  4. The investigation is conducted in compliance with the requirements for IRB review and informed consent (21 CFR 50, 56); and
  5. The investigation is conducted in compliance with regulations for the promotion and sale of investigational drugs (21 CFR 312.7).

   
A clinical investigation involving the use of a placebo is exempt from the requirement to obtain an IND if the investigation does not otherwise require submission of an IND.

 7.2.3 Emergency Use of An Investigational Drug or Biologic.
   


Emergency use is defined as the use of an investigational drug or biologic on a human subject in a life-threatening situation in which no standard acceptable treatment is available and in which there is not sufficient time to obtain IRB approval.

When a situation arises that, in the judgment of a physician, calls for the emergency use of an investigational drug or biologic in a single patient, an IND is still necessary. The usual procedure is to contact the manufacturer and determine if the drug can be made available for use (in this one patient) under the company's IND. Should the company elect not to name the physician as an investigator, the physician can contact the F.D.A. directly for an IND.

For drug products, the request should be directed to the Division of Drug Information (301) 827-4570. For biological blood products: Office of Blood Research and Review (301)827-3518.  For biological vaccine products:  Office of Vacine Research (301) 827-3070. After normal working hours the request should be directed to the Office of Crisis Management & Emergency Operations Center (301) 443-1240. Except in extraordinary circumstances, such authorization will be conditioned on the sponsor making an appropriate IND submission as soon as practicable after receiving authorization.

An investigational device may be used in an emergency if the institution or its IRB approved the use of the device in the particular situation. F.D.A. approval is not required but the sponsor should notify the F.D.A. when an investigational device has been used in such a situation.

Emergency use of an investigational drug, device or biologic product may be exempt from F.D.A. requirements for IRB review provided that such emergency use is reported to the IRB at the institution within five (5) working days. Any subsequent use of the investigational product at the institution is subject to IRB review.

The investigator is required to obtain informed consent of the subject or the subject's legally authorized representative unless both the investigator and a physician who is not otherwise participating in the clinical investigation certify, in writing, all of the following:


   
If the immediate use of a test article is required to preserve the life of the subject and there is insufficient time to obtain the independent determination required, the use of the test article must be reviewed and evaluated by an independent physician and the use of the test article reported to the IRB within five (5) working days.

Use of a test article in an investigation designed to be conducted under emergency conditions (e.g., emergency room research ) usually does not qualify for the emergency use exemption. In these circumstances, a protocol is designed well ahead of initiation of the study and ample time exists for IRBs to review the study and make provisions for informed consent.
  1. The subject is confronted by a life-threatening situation necessitating the use of the test article.
  2. Informed consent cannot be obtained because of an inability to communicate with, or obtain legally effective consent from, the subject.
  3. Time is not sufficient to obtain consent from the subject's legal representative.
  4. No alternative method of approved or generally recognized therapy is available that provides an equal or greater likelihood of saving the life of the subject.
If the immediate use of a test article is required to preserve the life of the subject and there is insufficient time to obtain the independent determination required, the use of the test article must be reviewed and evaluated by an independent physician and the use of the test article reported to the IRB within five (5) working days. Use of a test article in an investigation designed to be conducted under emergency conditions (e.g., emergency room research) usually does not qualify for the emergency use exemption. In these circumstances, a protocol is designed well ahead of initiation of the study and ample time exists for IRBs to review the study and make provisions for informed consent.

 7.2.4 Treatment Use of and Charging for Investigational Drugs
   
The FDA will permit the use of an investigational drug for treating patients outside of a controlled clinical trial under the following conditions:
  1. the drug is intended to treat a "serious" or "immediately life-threatening" disease;
  2. there is no comparable or satisfactory alternative drug or other therapy available to treat that stage of the disease in the intended patient population;
  3. the drug is under investigation in a controlled clinical trial under an IND in effect for the trial, or all clinical trials have been completed; and
  4. the sponsor of the controlled clinical trial is actively pursuing marketing approval of the drug with due diligence.

   

For "serious" diseases, the Commissioner of the FDA may deny a request for treatment use if there is insufficient evidence of safety and effectiveness to support such use. For "immediately life-threatening" diseases the Commissioner of the FDA may deny a request for treatment use if the available scientific evidence, taken as a whole, fails to provide a reasonable basis for concluding that the drug: (1) may be effective for its intended use in its intended population; or (2) would not expose the patients to an unreasonable and significant additional risk of illness or injury.

Treatment use of investigational drugs requires the investigator and the sponsor to comply with the safeguards of the IND process, including IRB review and informed consent.

With the approval of the FDA, sponsors may charge for investigational drugs under limited circumstances.

Expanded access regulations have been revised and broadened.  The regulations can be found at:
http://www.fda.gov/Drugs/DevelopmentApprovalProcess/HowDrugsareDevelopedand
Approved/ApprovalApplications/InvestigationalNewDrugINDApplication/ucm172492.htm


 7.2.5 Waiver of IRB Requirements
   
In very special circumstances - where it would be in the best interests of the subjects and where alternate mechanisms for assuring the protection of human subjects are adequate the F.D.A. may waive any of the requirements contained in the IRB regulations if requested by the sponsor or sponsor-investigator. The waiver provision does not apply to the informed consent requirement.
     
   


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