Transcript Sponsor vs. Investigator

INDs :
Does My Study Need One?
Edith Paal
UAMS Office of Research Compliance
526-6876
August 22, 2003
Scenarios
New drug that hasn’t been approved yet –
that’s an easy one. Yes, the study needs an
IND.
An approved drug used for a new
indication – this gets a bit trickier.
Using an approved drug for a
new indication
It can be prescribed it as part of regular
medical care with no problem.
But, say that after trying it in a few patients
as part of their standard care, you’ve gotten
promising results and you want to formally
study it.
Does the study need an IND?
21 CFR 312.2(b) (1) lists the
circumstances that, if all are met, make an
IND unnecessary.
Various guidances and draft guidances also
include more details about whether an IND
is required.
If ALL of these conditions are met, then
an IND is NOT required…
The study is not intended to support FDA
approval of a new indication or significant
change in the product labeling.
The study is not intended to support a
significant change in advertising for the
product.
(continued…)
If all of these conditions are met, then
an IND is NOT required…
The study is conducted in compliance with
IRB and informed consent regulations.
The study is conducted in compliance with
21 CFR 312.7, promotion and charging for
investigational drugs.
It does not intend to invoke 21 CFR 50.24,
(emergency research).
(continued…)
One last condition to meet…(and this is
the biggie)
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).
What might increase the risk, or
decrease the acceptability of the
risk?
Changing the dose level or the route of
administration
Is there a chance that subjects in a study
might receive a less effective treatment for
their condition than the standard of care?
The IND criteria for marketed oncology
drugs are a bit more flexible.
A draft guidance from the FDA addresses
oncology drugs specifically.
The National Cancer Institute’s Cancer
Therapy Evaluation Program’s
Investigator’s Handbook also has
information on INDs
http://ctep.cancer.gov/handbook/hndbk_1.html
Why are oncology drugs handled a bit
differently?
 In oncology practice, modifications of ordinary
dosing are not uncommon.
 Because of the way cancer drugs are used,
toxicity, even potentially lethal toxicity, is often
described in the approved labeling.
 Off-label therapy with cancer drugs is relatively
common in practice.
One step to take when trying to decide
if an IND is necessary
If you are changing the dose, route, or
schedule of administration, or you’re trying
a new combination of marketed drugs,
check the literature.
If no safety data of the changed dosage, route, schedule,
or new combination are available in the literature, you
probably need an IND.
Want a second opinion?
Call the FDA and ask for a written opinion.
But before you do that, call the Office of
Research Compliance. We can help you put
together what you’ll need to tell the FDA.
Phone Numbers
 FDA Drug Information Branch
301-827-4573
Barry Poole is the current contact there. He’s at
301-827-4570
 Phone numbers for other products are in the IRB
information sheet titled “Off-Label and
Investigational Use of Marketed Drugs,
Biologics, and Medical Devices”
Sponsor vs.
Sponsor-Investigator INDs
Carole Hamon
ACHRI Research Compliance
August 22, 2003
Sponsor
The sponsor takes responsibility for
and initiates a clinical investigation.
21 CFR 312.50
The sponsor may be a pharmaceutical
company, a private or academic
organization, or an individual.
Sponsor-Investigator
A Sponsor-Investigator is an individual
who both initiates and conducts a
clinical investigation and under whose
immediate direction the
investigational drug is being
administered or dispensed.
Caveats
For administrative reasons, only one
individual should be designated as
sponsor.
If a pharmaceutical company supplies
the drug, but does not submit the IND,
the company is NOT the sponsor.
Contract with supplier should define
who does what.
General Requirements for
INDs
FDA Form FD-1571
FDA Form FD-1572
Thirty day waiting period
21 CFR 312.40
FDA Form FD-1571
Twenty item form which must be
completed and signed by the SponsorInvestigator.
Willfully falsifying statements on this
form is a criminal offense.
FDA Form FD-1571- Box 12
HOWEVER, if the investigational drug
is prepared or altered in any way after
shipment by the supplier, complete
manufacturing (or compounding) and
controls information, including
information on sterility and pyrogenicity
testing for parenteral drugs, must be
submitted for that process in Box 7.
FDA Form FD-1572
This form is required for EVERY
physician or sub-investigator who is
going to be a part of the study and is
obtained BEFORE the release of drug
to the physician. This form satisfies the
requirements of Box 12, Item 6 b-d.
Overview of FDA Requirements
for Sponsor-Investigators
Review the applicable federal
regulations before performing any
sponsor duties
If you are a Sponsor-Investigator, you
MUST meet the requirements of both
the sponsor and the Investigator.
http://www.access.gop.gov/nara/cfr/wai
sidx_00/21cfr312_00.html
If you still want to be a
Sponsor-Investigator
The following needs to be in place
BEFORE you apply for the IND.
Monitoring and Compliance
Will select a monitor to oversee the
progress of the investigation.
21 CFR 312.53(d)
Will comply with FDA regulations
regarding emergency use of test
article.
21 CFR 312.54
Monitoring and Compliance
 Will keep investigators informed on the
safety and effectiveness of the drug.
21 CFR 312.55
 Need Data Safety Monitoring Board when
appropriate.
Monitoring and Termination
The Sponsor shall monitor the
progress of all clinical investigations
being conducted under their IND.
21 CFR 312.56(a)
The Sponsor shall terminate
investigator’s participation when
investigators fail to follow protocol.
21 CFR 312.56(b)
Drug Safety and
Effectiveness
The Sponsor shall review and
evaluate the evidence relating to
the safety and effectiveness of the
drug as it is obtained from each
investigator.
21 CFR 312.56(c)
Drug Safety & Effectiveness
The Sponsor shall discontinue the
study if the investigational drug
presents an unreasonable and
significant risk to subjects
The FDA, IRB, and all investigators
must be notified of the discontinuance.
21 CFR 312.56(d)
Reporting Requirements
Progress Reports – Your investigators
must furnish these to you as the
sponsor.
21 CFR 312.64(a)
IND Safety Reports – Adverse
Reactions
21 CFR 312.32
Annual Reports – Within 60 days of
anniversary of IND
21 CFR 312.33
Reporting Requirements
Final Reports – must obtain from your
investigators and submit to FDA
21 CFR 312.64(c)
Financial Disclosure Reports from
investigators must be received and
updated for one year post study
completion.
21 CFR 312.64(d)
Drug Accountability
The Sponsor must:
– Maintain adequate records showing
the receipt, shipment, or other
disposition of the investigational
drug.
21 CFR 312.57
–Assure that investigators return
all investigational drugs.
21 CFR 312.59
Drug Accountability
– Require investigators to maintain
adequate drug records.
21 CFR 312.62
– Require investigators to store the
investigational drug in a secure area.
21 CFR 312. 69
Label and Promotion
“Caution: New Drug – Limited by
Federal (or United States) law to
investigational use”
Promote and distribute the drug in
accordance with FDA regulations
21 CFR 312.7
IRB, Case Histories,
Payments
The sponsor must:
– require investigators to meet local
IRB requirements.
– maintain complete and accurate
records of payments made to clinical
investigators.
IRB, Case Histories,
Payments (cont’d)
– require investigators to keep case
histories on each individual
administered the investigational drug
or employed as a control in the
investigation.
Amendments
 Protocol Amendments
– New Protocol not already submitted
– Changes to a submitted protocol
21 CFR 312.30
 Information Amendments – Essential
information that is not within the scope of
a protocol amendment, IND safety
reports, or annual report.
21 CFR 312.31
New Protocol
Any study not covered by a protocol
already contained in the IND
May begin after two conditions are met
– The protocol has been submitted to the
FDA for its review
– The protocol has been approved by the
IRB in accordance with 21 CFR 56
21 CFR 312.30(a)
Changes to Submitted
Protocol
Phase 1 – any change significantly
affecting the safety of subjects
Phase 2 & 3 – any change significantly
affecting the safety of subjects, scope
of the investigation or the scientific
quality of the study.
21 CFR 312.30(b)
Information Amendments
New chemistry, toxicology, or other
technical information
Report of discontinuation of study
Submit as necessary but, to extent
feasible, not more than every 30 days.
21 CFR 312.31 (a-b)