INDIANA UNIVERSITY HEALTH
BLOOMINGTON
TITLE: Research With Investigational
Test Articles
APPROVED: Wanda Katinszky
ORIGINATION: 10/21/2013
IRB – INSTITUTIONAL REVIEW BOARD
POLICY NUMBER: RR 408
PAGE 1 OF 9
REVIEW WITH REVISION: 10/25/2013
REVIEW ONLY:
1. POLICY
The Code of Federal Regulations (CFR) Title 21 describes the procedures and requirements
governing the use of investigational new drugs (§312) and clinical investigations of devices
(§812). This SOP describes the policies at Indiana University Health Bloomington (IUHB) for
conducting research with these test articles, including the responsibilities of clinical
investigators and sponsors, when a clinical investigator assumes the sponsor function of an
investigational test article.
Pursuant to FDA regulations, investigators are responsible for ensuring that an investigation
is conducted according to the signed investigator statement or agreement, the
investigational plan, and applicable regulations, for protecting the rights, safety, and welfare
of subjects under the investigator’s care, and for the control of drugs and devices under
investigation.
2. POLICIES
2.1 Research Involving Investigational Drugs
2.1.1 Pursuant to 21 CFR 312.53(c)(1), an investigator must sign an investigator
statement (Form FDA-1572).
2.1.2 When the principal intent of the investigational use of a test article is to develop
information about the product's safety or efficacy, submission of an
Investigational New Drug (IND) application ordinarily must be submitted.
However, in certain circumstances, FDA does not require an IND.
2.1.3 Control of Investigational Drug. The Investigator shall administer the drug only to
subjects under the investigator’s personal supervision or under the supervision of
a sub-investigator responsible to the investigator. The Investigator shall not
supply the investigational drug to any person not authorized to receive it.
2.1.4 Recordkeeping and Record Retention
2.1.4.1 Disposition of Drug. The investigator is required to maintain adequate
records of the disposition of the drug, including dates, quantity, and use
by subjects. If the investigation is terminated, suspended, discontinued,
or completed, the investigator shall return the unused supplies of the
drug to the sponsor, or otherwise provide for disposition of the unused
supplies of the drug under §312.59. Unused study drug must not be
passed on to other investigator, used for animal research, or dispensed
to non-study subjects.
TITLE: Research With Investigational Test
Articles
REVIEW WITH REVISION: 10/25/2013
POLICY NUMBER: RR 408
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2.1.4.2 Case Histories. The investigator is required to prepare and maintain
adequate and accurate case histories that record all observations and
other data pertinent to the investigation on each individual
administered the investigational drug or employed as a control in the
investigation. Case histories include the case report forms and
supporting data including, for example, signed and dated consent forms
and medical records, including for example, progress notes of the
physician, the individual’s hospital chart(s), and the nurses’ notes. The
case history for each individual shall document that informed consent
was obtained prior to participation in the study.
2.1.4.3 Record Retention. The investigator shall retain records required to be
maintained for a period of 2 years following the date a marketing
application is approved for the drug for the indication for which it is
being investigated; or, if no application is to be filed or if the application
is not approved for such indication, until 2 years after the investigation
is discontinued and FDA is notified.
2.1.5 Investigator Reports
2.1.5.1 Progress Reports. The investigator shall furnish all reports to the sponsor
of the drug who is responsible for collecting and evaluating the results
obtained.
2.1.5.2 Safety Reports. The investigator shall promptly report to the sponsor any
adverse effect that may reasonably be regarded as caused by, or
probably caused by, the drug. If the adverse effect is alarming, the
investigator shall report the adverse effect immediately.
2.1.5.3 Final Report. The investigator shall provide the sponsor with an adequate
report shortly after completion of the investigator’s participation in the
investigation.
2.1.5.4 Financial Disclosure Reports. The investigator shall provide the sponsor
with sufficient accurate financial information to allow an applicant to
submit complete and accurate certification or disclosure statements as
required under 21 CFR 54. The investigator shall promptly update this
information if any relevant changes occur during the course of the
investigation and for 1 year following the completion of the study.
2.1.6 Inspection of Investigator’s Records and Reports. The investigator shall, upon
request from any properly authorized officer or employee of FDA, at reasonable
times, permit such officer or employee to have access to, and copy and verify
any records or reports made by the investigator pursuant to §312.62,
Investigator Recordkeeping and Record Retention. The investigator is not
required to divulge subject names unless the records of particular individuals
require a more detailed study of the cases, or unless there is reason to believe
TITLE: Research With Investigational Test
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REVIEW WITH REVISION: 10/25/2013
POLICY NUMBER: RR 408
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that the records do not represent actual case studies, or do not represent actual
results obtained.
2.1.7 Handling of Controlled Substances. If the investigational drug is subject to the
Controlled Substances Act, the investigator shall take adequate precautions,
including storage of the investigational drug in a securely locked, substantially
constructed cabinet, or other securely locked, substantially constructed
enclosure, access to which is limited, to prevent theft or diversion of the
substance into illegal channels of distribution.
2.2 Sponsor-Investigator Responsibilities for Research Involving Investigational Drugs.
Pursuant to §312.3(b), a Sponsor-Investigator is an individual who both initiates and
conducts an investigation, and under whose immediate direction the investigational
drug is administered or dispensed. When an investigator assumes the sponsor function,
there are additional responsibilities.
2.2.1 Investigational New Drug Application (IND)
2.2.1.1 When the principal intent of the investigational use of a test article is to
develop information about the product's safety or efficacy, submission
of an Investigational New Drug (IND) application ordinarily must be
submitted. However, in certain circumstances, FDA does not require an
IND.
2.2.1.2 The sponsor-investigator shall submit an IND to the FDA if he/she
intends to conduct a clinical investigation with an investigational new
drug that is subject to §312.40.
2.2.1.3 The sponsor-investigator shall not begin a clinical investigation subject
to §312.2(a) until the investigation is subject to an IND which is in effect
in accordance with §312.40.
2.3 Investigational Drug Services
2.3.1 All INPATIENT studies conducted at an IUHB facility should use the services of the
facility’s pharmacy department. The only exception is if the investigator, after
consultation with the pharmacy, determines that he/she has adequate
manpower, facilities, knowledge, and time to assume all the responsibilities the
pharmacy would have provided.
2.3.2 OUTPATIENT studies are not required to, but may use the pharmacy, if they wish.
Using the services of the pharmacy is strongly recommended for studies
involving the use of an investigational drug:
2.3.2.1 that requires preparation in a sterile hood (All IV drugs); and
2.3.2.2 that requires admixing of any kind.
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2.3.3 Receipt and Inventory of Study Drug. Upon receipt of an investigational drug, the
investigator or other designated individual should document that information on
the packing slip matches what was sent to the site, including the amount, lot
numbers, and quantity. Any discrepancies, damage, or tampering should be
reported promptly to the Sponsor.
2.3.4 Prescribing and Dispensing of Study Drug. Study drugs may only be dispensed by
authorized individuals according to state and federal regulations, and
hospital/facility policies. If an investigator will be dispensing an investigational
drug for an outpatient study, the following should be documented in the protocol
and carried out during the study:
2.3.4.1 Individuals authorized to prescribe and/or dispense the study drug.
These individuals must be listed in the investigators list and FDA Form
1572, as applicable. A record of authorized individuals’ signatures and
initials should be maintained at all times.
2.3.4.2 Documentation of the order or prescription, e.g. order form, script,
signed by authorized individuals. Study drug should only be dispensed
according to the dose, route, and frequency written in the order.
2.3.4.3 Documentation of any changes, titrations, or deviations made to dosing
orders or protocol dosing, along with the signature(s) of authorized
individuals. Dosing changes or deviations from the protocol should only
be made to protect the subject and should be reported to the IRB
according to the Unanticipated Problems and Noncompliance SOP.
2.3.4.4 Each time study drug is dispensed, documentation should be made of
the amount and to whom it was dispensed, and the date and signature
(or initials) of the individual dispensing the study drug. Subjects should
be instructed in the proper storage, use, precautions, and potential risks
of the study drug.
2.3.4.5 Subjects should be advised to return all study drug containers (used and
unused) to the original study drug dispensation site, unless other means
of disposition have been approved. Study personnel should record the
amount, e.g. number of bottles/pills, and date of return. If a subject
does not return study drug containers, study personnel should
document attempts to retrieve them from the subject, including a
certified letter, if necessary.
2.3.4.6 Discrepancies in amounts of study drug used and returned (actual and
suspected) by the subject should be documented, along with the
reason(s) for the discrepancy. Major discrepancies should be followedup on with the subject and/or pharmacy to obtain an explanation.
2.3.4.7 Authorization from the Sponsor is required for dispensing study drug in
special circumstances.
TITLE: Research With Investigational Test
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REVIEW WITH REVISION: 10/25/2013
POLICY NUMBER: RR 408
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2.3.4.8 If the drug is to be administered at a site that is not listed on the FDA
Form 1572 and the Study Summary Statement, approval must first be
obtained from the Sponsor and the IRB to do so.
2.3.5 Storage of the Study Drug. The study drug should be stored in a secure
environment, e.g. locked cabinet in a locked area, with access limited to
authorized research personnel. The study drug should be stored at the
appropriate temperature while maintaining a temperature log, if appropriate.
2.3.6 If a subject in an OUTPATIENT study requires hospitalization and the study drug
needs to be administered during the subject’s hospital stay, a physician caring
for the subject should write an order allowing the subject to continue taking the
study drug from his/her own supply. The order should clearly document that the
subject is enrolled in a study using an investigational drug. The pharmacy should
also be notified of the subject’s hospitalization, if its services are being used for
the study.
2.4 Research Involving Investigational Devices
2.4.1 Pursuant to 21 CFR 812.43(c)(4), an investigator must sign an agreement, which
commits him/her to certain requirements.
2.4.2 When the IRB determines that the device is a significant risk device, the
investigator must confirm that the device has an investigational device
exemption (IDE) issued by FDA, the device fulfills the requirements for an
abbreviated IDE, or the protocol meets one of the FDA exemptions from the
requirements to have an IDE.
2.4.3 Receipt and inventory of study device. This section applies to those study devices
the investigator dispenses/administers to the study subject. The investigator (or
designated research associate) is responsible for ensuring that:
2.4.3.1 Upon receipt (preferable within 2 working days, but definitely prior to
dispensing) of the study device, inventory the shipment, ensuring that
the information on the packing slip matches exactly with what has been
sent to the site, including the receipt date, lot numbers, device type,
batch number, code mark, and quantity. Additionally, the identification
of the person who received the shipment of devices should be noted.
Documentation of this shipment inventory should be maintained.
2.4.3.2 Promptly (usually within 2-3 working days) bring any discrepancies to
the attention of the Sponsor/supplier of the device(s).
2.4.3.3 Retain a copy of the shipping inventory, packing slips and document
inventory in the study files.
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2.4.3.4 Maintain an accountability log (most Sponsors will issue/supply a device
accountability log).
2.4.4 Study Device Labeling
2.4.4.1 Study devices from Sponsor companies are pre-labeled and these
should not be defaced, relabeled or changed in any way without written
permission of the Sponsor. It is recommended that an additional label
may be placed to include the study staff contact name/number, but
ONLY if the Sponsor agrees.
2.4.4.2 If the Principal Investigator is responsible for labeling, he/she should be
aware of applicable FDA regulations. Examples of what may appear on
a label are: name of device, model number, serial number, and
manufacturer.
2.4.4.3 When a study device is designated as “Investigational” per FDA
regulations, there should be a label with the following information:
• Name and place of business of the manufacturer, packer, or
distributor.
• Quantity of contents if appropriate, and the following statement:
“CAUTION-Investigational device. Limited by Federal (or United
States) law to investigational use.”
• The label or other labeling shall describe all relevant
contraindications, hazards, side effects, interfering substances
or devices, warnings, and precautions.
2.4.5 Storage of the Study Device (including devices that record data from automated
instruments)
2.4.5.1 Establish and maintain access controls for essential and appropriate
research personnel.
2.4.5.2 Develop procedures for verifying physical access.
2.4.5.3 Store the study device in a secure environment to include locks on doors
and controlled access.
2.4.5.4 Establish equipment control both into and out of the research site.
2.4.5.5 Develop Security Incident Procedures to report any privacy breaches.
2.4.5.6 Assess any privacy risks anticipated and develop methods to avoid those
risks.
2.4.5.7 Develop data backup, storage, and emergency mode procedures, if
applicable.
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REVIEW WITH REVISION: 10/25/2013
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2.4.5.8 Ensure the study device is stored at the appropriate temperature, and
maintain a storage area temperature log, if appropriate.
2.4.6 Dispensing of Study Devices
2.4.6.1 The investigator shall permit an investigational device to be used only
with participants under his/her personal supervision or under the
supervision of a co-investigator responsible to the investigator.
2.4.6.2 The investigator shall not use or supply an investigational device to
any person not authorized to receive it.
2.4.6.3 Create an access log to document each time the study device is
dispensed/used, where it is dispensed/used, to whom it is
dispensed/used, and the date and signature or initials of the
person dispensing/using the study device, (plus any other information
dictated by the study protocol).
2.4.7 Return/Destruction of Study Device (as applicable to the specific device)
2.4.7.1 At the conclusion of the study, ensure that all documentation regarding
receipt, storage, dispensing, return of used containers, and
accountability is complete and accurate.
2.4.7.2 An explanation of why and how many device units have been returned to
the sponsor, repaired, or otherwise disposed of should be noted. When
a device is disposed of, the identification of the person who doing so
should also be noted.
2.4.7.3 Devices obtained from a Sponsor for the specific purpose of a research
study must be returned to Sponsor. Only with the written authorization
(i.e. in the protocol or other written correspondence) of the Sponsor (and
in compliance with Federal regulations and Institutional policies) may
the investigator discard the device on site, or retain the device.
2.4.7.4 Pursuant to 21 CFR 812.110, upon completion or termination of a
clinical investigation or the investigator’s part of an investigation, or at
the sponsor’s request, an investigator shall return to the sponsor any
remaining supply of the device or otherwise dispose of the device as the
sponsor directs.
2.4.7.4.1 Unused study devices that include individually identifiable
health information must not be transferred to other
investigators without IRB approval or an authorization from
the study subject.
2.4.7.4.2 Unused study devices without individually identifiable health
information must not be transferred to other investigators,
used for animal research, or dispensed to non-study patients
TITLE: Research With Investigational Test
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REVIEW WITH REVISION: 10/25/2013
POLICY NUMBER: RR 408
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unless written consent is obtained from the Sponsor/Provider
of the device.
2.4.7.5 Device study records must be kept for a duration of seven
years (according to federal regulations and the IUHB SOP on
Data Management).
2.5 Research on FDA-approved Devices for FDA-approved Indications
2.5.1 Requires documentation of receipt, storage, dispensing and return of the
device as above.
2.5.2 The FDA approved label is adequate, although including information specific
to the study is recommended.
2.6 Radiologics
Radiation-emitting devices have similar requirements as above. However, there may
be specific requirements based on the device and the study design and thus each
study should be discussed with the Radiation Safety Officer at the Institution where
the study is conducted.
3. SCOPE
This SOP applies to all drug and device studies that involve human subjects, which are
approved by the IU Health Bloomington IRB. This includes, but is not limited to, Sponsored
and Investigator initiated studies, with or without an Investigational New Drug (IND) or
Investigational Device Exemption (IDE).
4. RESPONSIBILITY
Principal investigators are responsible for assuring that appropriate implementation of
investigational device accountability is maintained per these policies and procedures.
5. APPLICABLE REGULATIONS AND GUIDELINES
21 CFR 812 Investigational Device Exemptions
http://www.access.gpo.gov/nara/cfr/waisidx_02/21cfr812_02.html
4.2 21 CFR 814 Pre-Market Approval of Medical Devices
http://www.access.gpo.gov/nara/cfr/waisidx_02/21cfr814_02.html
45 CFR 164.530(c)(1) Administrative Requirements, Safeguard
http://a257.g.akamaitech.net/7/257/2422/14mar20010800/edocket.access.gpo.gov/cfr
_2002/octqtr/45cfr164.530.htm
Center for Devices & Radiological Health (CDRH)
http://www.fda.gov/cdrh/
Medical Device Reporting Alternative Summary Reporting (ASR) Program
http://www.fda.gov/cdrh/osb/guidance/315.html
TITLE: Research With Investigational Test
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REVIEW WITH REVISION: 10/25/2013
POLICY NUMBER: RR 408
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6. REFERENCES TO OTHER APPLICABLE SOPS
This SOP affects all other SOPs.
7. Attachments - None
8. PROCESS OVERVIEW
The section describes the procedures as it relates to the accountability of Investigational
Drugs and Devices approved by the IU Health Bloomington IRB.
9. PROCEDURES EMPLOYED TO IMPLEMENT THIS POLICY
Who
Task
Investigator
The investigator must familiarize himself/herself
to their responsibilities related to conducting
research with an investigation test article: drugs
or devices
Tool