Transcript Slide 1
educate • fund • connect • support
MIAP – Introduction to INDs and IDEs
E Mitchell Seymour, PhD RAC
Research Faculty
Regulatory Project Manager
educate • fund • connect • support
MICHR is here to enable & enhance clinical &
translational research. We do this by being a
catalytic partner who educates, funds,
connects, and supports research teams at U-M.
educate • fund • connect • support
Created in 2006, awarded a $55M CTSA grant
from the NIH in 2007, and renewed in May
2012, MICHR is part of a consortium of CTSA
institutions working together to
accelerate discoveries toward better health.
Why
MICHR serves the entire U-M campus.
educate • fund • connect • support
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MICHR Research Support
Services
Michigan Clinical Research Unit
IND/IDE Regulatory Assistance
Biostatistical Design & Analysis
Study Monitoring
Database Development
Study & Data Management
Mentoring
Clinical Trials Office
Clinical Research Informatics Tools
“MICHR IND/IDE INVESTIGATOR ASSISTANCE
PROGRAM”
MIAP
Regulatory assistance with IND/IDE
application submission & support
What is the definition of a drug?
“Articles intended for use in the diagnosis, cure,
mitigation, treatment, or prevention of
disease…” and
“Articles (other than food) intended to affect the
structure or any function of the body of man or
other animals”
What constitutes a drug?
Exogenous compounds (small and large molecule,
organic and inorganic)
Endogenous compounds
Live organisms
Cosmetics
Food (when used/applied in a certain way…)
Dietary supplements
Conventional foods
Applicable Regulations
The Federal Food, Drug, and Cosmetic Act (FD&C Act) gives
the FDA authority to regulate drugs and devices
Drugs/Biologics
Code of Federal Regulations (CFR)
21 CFR Part 312: Investigational New Drugs (IND)
Devices
Code of Federal Regulations (CFR)
21 CFR Part 812: Investigational Device Exemptions (IDE)
Academic Research – “Investigator” vs.
“Sponsor-Investigator”
Sponsor is an individual, company, academic institution, or other
organization that takes responsibility for and initiates a clinical
investigation. The sponsor is not the “funding organization” by FDA
definitions.
Investigator is an individual under whose immediate direction a
drug/device is administered or dispensed.
Sponsor-Investigator is an individual who both initiates and conducts an
investigation. The requirements/responsibilities under this part include
both those applicable to an investigator and a sponsor. SponsorInvestigators must also conclude or close investigations.
When is an IND Needed??
Sponsor-Investigator intends to conduct a clinical
study with an investigational drug
Sponsor-Investigator intends to conduct a study
with an approved drug, but…
In a new indication/population
Dosage form OR
Dosage range that is not covered in the current package insert
(off label)
Changed Risk of Product and/or to
Population
Route of Administration
Drug approved for oral administration is going to be given
intravenously
Dose
Increases in dose, frequency, or duration of administration can
increase risk
Decrease in dose can also increase risk
Patient Population
Adult to children
Moving from very ill population to a less ill population
IND Exemption Criteria
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 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 and with the requirements for informed consent.
The investigation is not intended to promote or commercialize the drug
product.
January 2004
http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/
Guidances/UCM071717.pdf
October 2010
http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM229175.pdf
What Information is Submitted in an IND
Application?
Clinical Protocol
Draft Informed Consent Document
Draft Case Report Forms
PI CV (signed and current, dated)
Investigator Brochure (for investigational study drug, also for multisite studies with an approved drug)
Labeling information (for approved drug)
Letter of Authorization (LOA) to Cross-reference the approved drug
Relevant reference articles
IND Application Content Requirements
per 21 CFR 312.2
* Not required for Sponsor-Investigator
INDs for single-site studies
Cover Sheet (FDA Form 1571)
Table of Contents
Introductory statement and General Investigational Plan
Investigator Brochure* (provided by the company or by investigator)
Study Protocol and Informed Consent
Chemistry, Manufacture, and Control Information (can be via LOA, IB)
Pharmacology and Toxicology Information (can be via LOA, IB)
Previous Human Experience (can be via LOA, IB)
Additional Information (draft Case Report Forms, pertinent professional
guidances, manuscripts)
Written by or provided by the investigative team!
IND Maintenance
IND Amendments
Protocol Amendments
New protocol
Changes in protocol
New investigator
Information Amendments
New toxicology, chemistry, or other technical information
New Investigator’s Brochure
IND Safety Reports
Unexpected fatal or life threatening suspected adverse reactions – 7 calendar days
Unexpected serious suspected adverse reactions – 15 calendar days
IND Annual Reports
Submitted to FDA within 60 calendar days of the IND Anniversary Date
Expanded Access to Investigational Drugs
Types of Expanded Access
Single-patient - Emergency Use
Single-patient - Non-emergency Use
Intermediate-size patient populations
Treatment IND or treatment protocol
Devices
The first regulatory hurdle…
“Significant Risk”, or “Non-significant Risk”?
January 2006
http://www.fda.gov/downloads/RegulatoryInformation/Guidances/UCM126418.pdf
Who Decides Whether a Device is SR or
NSR?
Sponsor-Investigator
- makes the initial risk determination
- presents the IRB with this information
IRBs
Required to determine whether the device study involves a SR or NSR device. For
an investigational device that is considered to be non-significant risk, the IRB can
approve the “IDE”.
FDA
Is available to help, and is the final arbiter!
What is the sponsor’s responsibility to
the IRB for NSR device studies?
Provide reviewing IRB(s) with an explanation of why the
device is not a SR
- Description of device
- Reports of prior investigations
- Proposed investigational plan
- Subject selection criteria
Inform IRB if FDA determined the study to be NSR
A Significant Risk 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.
Non-significant Risk (NSR) Devices
NSR devices are devices that do not pose a potential for serious risk to
the human subjects.
A NSR device study requires only IRB approval prior to initiation of a
clinical study. Sponsors of studies involving NSR devices are not required
to submit an IDE application to FDA for approval. Submissions for NSR
device investigations are made directly to the IRB of each participating
institution.
If the IRB disagrees and determines that the device poses a SR, the
sponsor must report this finding to FDA within five working days
[§812.150(b)(9)].
FDA considers an investigation of a NSR device to have an approved IDE
when IRB concurs with the NSR determination and approves the study.
What are the Requirements for NSR Device
Studies?
Abbreviated requirements per 21CFR 812.2(b)
Labeling
IRB approval
informed consent
monitoring
record keeping
reports
prohibition against promotion.
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NSR studies are considered to have an approved IDE therefore no IDE to FDA
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Sponsors and IRBs do not have to advise FDA of NSR device studies
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IRBs must make a SR or NSR determination for every NSR study (21 CFR 812.66)
IDE Exempt if:
Used in accordance with indications/labeling
Non-invasive diagnostic
Consumer preference testing
Solely for veterinary use
Research on or with lab animals
IDE Application Content Requirements
per 21 CFR 312.2
Written by or provided by the investigative team!
(1) The name and address of the sponsor.
(2) A complete report of prior investigations of the device and a complete investigational plan (Protocol)
(3) A description of the methods, facilities, and controls used for the manufacture, processing, packing, storage, and,
where appropriate, installation of the device
(4) An example of the agreements to be entered into by all investigators to comply with investigator obligations under this
part, and a list of the names and addresses of all investigators who have signed the agreement.
(5) A certification that all investigators who will participate in the investigation have signed the agreement, that the list of
investigators includes all the investigators participating in the investigation, and that no investigators will be added to the
investigation until they have signed the agreement.
(6) A list of the name, address, and chairperson of each IRB that has been or will be asked to review the investigation and
a certification of the action concerning the investigation taken by each such IRB.
(7) The name and address of any institution at which a part of the investigation may be conducted
(8) If the device is to be sold, the amount to be charged and an explanation of why sale does not constitute
commercialization of the device.
(9) An environmental assessment (if applicable) or claim of exemption therefrom
(10) Copies of all labeling for the device.
(11) Copies of all forms and informational materials to be provided to subjects to obtain informed consent.
(12) Any other relevant information FDA requests for review of the application.
Providing valuable support
services for research studies
MICHR IND/IDE Investigator Assistance Program
(MIAP)Provides Comprehensive:
Regulatory Expertise…
Regulatory Support…
Regulatory Education…
…to Investigators and their Team involved in FDA-regulated
research.
MIAP Team
[email protected]
Jeanne Wright
MIAP Lead
[email protected]
Kevin Weatherwax
Manager, MIAP
[email protected]
Mona Moore
MIAP Team Member
[email protected]
E. Mitchell Seymour, PhD
MIAP Team Member
[email protected]
Bill Reisdorph
MIAP Team Member
[email protected]
MIAP Team
• Various certifications from the Regulatory Affairs Professional Society,
the Association of Clinical Research Professionals, the Society of
Clinical Research Associates, the National Association of IRB
Managers, and the American Society for Quality.
• Varied backgrounds in academia and industry with expertise in life
sciences, chemistry (drug discovery R&D), nursing, Human Subjects
Research Protection, Good Clinical Practice, Good Laboratory Practice,
Good Manufacturing practice, quality assurance, and clinical trial
operations.
• Mean year professional experience = 26.3
Research (clinical + preclinical) = 15.2
Regulatory Affairs = 10.5
MIAP SERVICES OVERVIEW
Agent/Device
development/regulatory strategy
consultation
IND/IDE consultation including
determination of need for IND or
IDE
Pre-IND/IDE FDA meeting requests
and support
Clinical hold/conditional approval
response preparation/submission
Communication with the FDA, IRB
and other regulatory bodies
IND/IDE “maintenance” support
– Safety report submissions
– Protocol amendments
Protocol/Informed Consent review
– Annual reports
IND/IDE application preparation
and submission to FDA
– Investigator Amendments
– Informational Amendments
Contact us!
[email protected]
https://www.michr.umich.edu/services/regulatorys
upport/miap
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