CUMC IRB Investigator Meeting

Special IND/IDE Considerations:Emergency Use of Investigational Product

Compassionate Use& Emergency Research

July 21, 2005

July 21, 2005 Page 2

Objectives

Today’s session will provide information on:

• Understanding of Regulatory Requirements and Considerations

• Understanding the Options of Treating Patients with Experimental Therapies

• How to Prepare an Application to the IRB for Emergency Research

• How to Conduct Community Consultation

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FDA Regulations

Code of Federal Regulations:

-Title 21, Parts 50.23

-Title 21 CFR 50.24

-Title 21 CFR 312

-Title 21 CFR 812

Guidance:

-Humanitarian Use Device Exemptions

-Guidance on IDE Policies and Procedures

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Federal Regulations for the Protection of Subjects from Research Risks

45 CFR Part 46

Subpart A -- Basic Protections

Subpart B -- Pregnant Women, Neonates and Fetuses

Subpart C -- Prisoners

Subpart D -- Children

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Emergency Use of an

Investigational Drug or Device

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Emergency Use of an Investigational Drug or Device

-Medical care with investigational product, not research

-Only allowed in emergency, life-threatening situations, when:-no alternative standard treatment is available-another physician concurs with the assessment that the

situation is life-threatening and no alternative std. tx is available

-all efforts should be made to obtain informed consent

-Allowed for ONE time use; subsequent use requires Prospective IRB Approval (CAUTION: Trigger for FDA Audit)

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Emergency Use of an Investigational Drug or Device

-Distinction between life-threatening and site-threatening-Site threatening (i.e., loss of organ) may be allowed

-Should always consult with sponsor (i.e., IND/IDE holder) prior to use of the product in a life-threatening situation

-Data may not be used for research purposes

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Emergency Use of an Investigational Drug or Device

-Sponsor or Pharmacy may request approval from the IRB

-IRB will not approve, but will provide authorization letter in accordance with 56.104 and 50.23;

-IRB authorization letter should be generated within 3 hours upon submission of all necessary information;

-patient’s initials;-drug or device name;-patient’s diagnosis/indication for drug or device

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Emergency Use of an Investigational Drug or Device

After use of the drug or device:

Within 5 days, must submit the following to the IRB (by letter, not in RASCAL):

-documentation that the case was a life-threatening situtation;-concurrence of another physician;-whether or not informed consent was obtained; and if not, what efforts were made to obtain consent;

-submit protocol and consent form to the IRB for review if there is any expectation of a future use of the drug or device.

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Compassionate Use with an

Investigational Drug or Device

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Compassionate Use of an Investigational Drug or Device

-Generally, intent of providing therapy or treatment to a patient that would not be available in standard practice AND the subject does not qualify for a research study;

-Generally, does not fit the emergency, life-threatening criteria.

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Compassionate Use of an Investigational Drug or Device

-Needs prospective IRB approval and therefore needs a submission in RASCAL;

-Needs informed consent obtained in accordance with IRB requirements;

-Should have a sponsor’s protocol and investigator’s brochure attached;

-Should clearly state that the effort is primarily compassionate use and not research and state if time is of the essence.

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Compassionate Use of an Investigational Device

Some flexibilities are offered by FDA guidances on devices:

Humanitarian Device Exemption Regulation: Questions and Answers: Final Guidance for Industry (July 12, 2001)

http://www.fda.gov/cdrh/ode/guidance/1381.html

Guidance on IDE Policies and Procedures (January 20, 1998)

http://www.fda.gov/cdrh/ode/idepolcy.html

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Compassionate Use of an Investigational Device Flexibilities Offered

Humanitarian Device Exemption Regulation: Questions and Answers: Final Guidance for Industry (July 12, 2001)

-HUD may be used for compassionate use;

-Consult with sponsor/IDE holder;

-Physician should ensure patient protection measures are addressed;-If Research, then submit application in RASCAL;-If Medical Care w/o Research, submit a letter to the IRB (consult with

IRB first)

-Prior FDA approval is required.

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Compassionate Use of an Investigational Device Flexibilities Offered

Guidance on IDE Policies and Procedures (January 20, 1998) – Chapter III, Expanded Access to Unapproved Devices:

Individual Patient Access to Investigational Devices Intended for Serious Diseases (falls under 812.35 Supplemental Applications):

-Consult with sponsor/IDE holder;-Physician should ensure patient protection measures are addressed;

-If Research, then submit application in RASCAL;-If Medical Care w/o Research, submit a letter to the IRB (consult with

IRB first);-Concurrence from IRB Chair (not approval) is required;-Prior FDA approval is required.

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Emergency Research with an

Investigational Drug or Device

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Belmont Report, 1979

Articulates 3 Basic Ethical Principles:

Respect For Persons – Autonomy of the Individual

Beneficence – Risk Minimization

Justice – Burdens and Benefits of Research are Equitably Distributed

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Emergency Research with an Investigational Drug or Device

Exception from informed consent requirements for emergency research (21 CFR 50.24, October 2, 1996):

-Regulations require many additional considerations during IRB review

-See Handout

http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?fr=50.24

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Emergency Research with an Investigational Drug or Device

Community Consultation

-Required under 21 CFR 50.24

-discussions with, and soliciting opinions from the community/ies in which the study will take place and from which the study subjects will be drawn.

-may not always be the same; when they are not the same, both communities should be consulted.

-an IRB member or representative should attend these discussions so that they have first-hand knowledge of community reaction.

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Emergency Research with an Investigational Drug or Device

Community Consultation

FDA Guidance:

http://www.fda.gov/ora/compliance_ref/bimo/err_guide.htm#COMMUNITY

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Emergency Research with an Investigational Drug or Device

Community Consultation

Samples of community consultation done by Mayo Clinic:

http://www.fda.gov/ohrms/dockets/dailys/04/aug04/083004/95s-0158-sup0028-04-Mayo-Clinic-Rochester-NM-vol28.pdf