The Office of Research Compliance and Regulatory Affairs
A Basic Research Compliance Handbook
What you need to know about Research Compliance at UC
Table of Contents
ORCRA Mission Statement 3
ORCRA Quick Reference 4
Human Subjects Research Protection 6
Post Approval Monitoring 19
IND/IDE (FDA regulated research) Assistance Program 22
Vertebrate Animal Research 26
Radiation Safety 40
Compliance Training 43
Requirements for DEA License 44
Compliance Hot Line 45
The Office of Research Compliance and Regulatory Affairs covers:
• Human subject protection – IRB
• Post IRB approval monitoring- PAMP
• Investigational new drug/device Assistance Program- IAP
• Animal welfare & protection – IACUC
• Recombinant DNA &/or infectious agents –Biosafety & IBC
Research Compliance Officer: Jane E. Strasser, Ph.D.
Director ORCRA 51 Goodman Avenue
Suite 540, ML0567
Cincinnati, OH 45221-0567
Website information: http://researchcompliance.uc.edu
ORCRA's goal is to facilitate research while protecting the university, it students, and
staff. The mission of ORCRA is one of service, to both the University of Cincinnati and
to the faculty and staff. Our main focus is to ensure the safety of research involving
human and animal subjects, the safe use of hazardous biologicals and to maintain
University compliance with all Federal, State and Local regulations. We are here to help
and promise to work with you, to be proactive in ensuring that all researchers are
appropriately following existing guidelines, and to do so in the least burdensome way
ORCRA Quick Reference:
Human Subjects’ Research Protection
General Inquiries: IRB Office Manager, Anthony Gardner, 558-5105
Post Approval Monitoring
General Inquiries: PAMP Interim Director, Angela Braggs-Brown, RAC, 558-3005
IND/IDE Assistance Program
General Inquiries: Angela Braggs-Brown, RAC, 558-3005
General Inquiries: IACUC Office Director, Rob Anderson, CPIA , 558-5106
Biosafety (IBC) Offfice
General Inquiries: Biosafety Officer, Marcia Espinola, DVM CBSP, 558-6182
Chemical Safety: Environmental Health and Safety
General Inquiries: Director, EHS, Jan Utrecht, M.S., 556-4968
Radiation Safety Office
General Inquiries: Radiation Safety Officer, Victoria Morris, 558-4110
For Questions regarding online research compliance training
Contact Dawn O'Neill, 558-6565
Toll-free Anonymous Compliance Hotline 1-800-889-1547
Or anonymous email
ORCRA publishes a Quarterly Newsletter with news and information from each of our
divisions. Use the email address below if you would like to be on the distribution list
Newsletters are archived on the website at http://researchcompliance.uc.edu
Human Subjects Research Protection
UC's IRB is AAHRPP Accredited
What is Human Subjects’ Research?
Human subjects’ research means any activity intended to obtain and record information
from or about individuals for research purposes. Any undertaking in which students,
faculty, or staff investigate and/or collect data on human subjects or use existing data or
specimens collected from living human subjects for research purposes, requires review by
the Institutional Review Board prior to initiation of the project. This includes both funded
and non-funded research, including dissertations, masters’ theses, pilot studies, class
projects, and non-funded, faculty-directed research if the following conditions are
• the research is sponsored by the University, or
• the research is conducted by or under the direction of any University
• agent of this institution in connection with his/her institutional
• the research is conducted by or under the direction of any University
• agent of this institution using any University property or facility, or
• the research involves the use of the University's non-public information to
• identify or contact human research subjects or prospective subjects
Requirements for Conducting Research
Involving Human Subjects
Human subjects research at the University of Cincinnati is conducted according to a
Federal wide Assurance (FWA), unless exempt.
The FWA requires that research proposals be reviewed by a convened committee
known as the Institutional Review Board (IRB).
Some examples include:
• mechanisms of human disease
• therapeutic interventions
• clinical trials
• epidemiologic and behavioral studies
• outcomes research
• research using human specimens and or data including
o bodily materials (cells, blood, tissues
o residual diagnostic specimens (Path samples)
o private medical information
Human Subjects Research Policies
AAHRPP DOMAIN I - ORGANIZATION
AAHRPP DOMAIN II - RESEARCH REVIEW UNIT
AAHRPP DOMAIN III - INVESTIGATOR
AAHRPP DOMEIN IV - SPONSORED RESEARCH
AAHRPP DOMAIN V - PARTICIPANT OUTREACH
There are policies for each of the elements as required by AAHRPP. The link above,
HPR Policies, will take you directly to the most current version of each domain
Criteria for Human Research
Does my study fit the requirements?
DETERMINING WHETHER AN ACTIVITY IS HUMAN SUBJECTS
RESEARCH AS DEFINED BY FEDERAL REGULATIONS
Any proposed activity involving contact with live persons, which involves UC faculty,
staff, students, and qualifies as human subjects research1 must be submitted for IRB
review and approval prior to initiation of the activity.
The IRB Chair for the Medical Board and the IRB Chair Social and Behavioral Board are
responsible for determining whether the research constitutes human subjects research.
Questions about the nature of an activity as potential human subjects research should be
discussed with the Chair of the Institutional Review Board before beginning the activity.
All human subjects research must be submitted to the UC IRB for review prior to
initiation of the activity.
If the answer is yes to both of these questions, the activity must be submitted to the IRB
for further evaluation prior to initiation of the activity.
1. Is the activity a systematic investigation2 or clinical investigation3, including
protocol development, testing, and evaluation, designed to contribute to
2. Does the activity involve living individuals5 about whom the investigator obtains
data through intervention6 or interaction7 with the individual, or obtains
identifiable8 private information9?
In addition, if the answer is yes to any of the following questions the activity must be
submitted to the IRB for further evaluation prior to initiation of the activity.
1. Does the activity involve the use of a drug (including an approved drug or an
over-the-counter drug), other than the use of an approved drug in the course of
2. Does the activity involve the use of a medical device (including an approved
medical device), other than the use of an approved medical device in the course of
medical practice? (Note that medical devices generally include devices intended
for the use in the diagnosis of disease or other conditions, or in the cure,
mitigation, treatment, or prevention of disease, in humans or other animals, and
devices intended to affect the structure or any function of the body of humans or
3. Will data be submitted to the FDA or held for their inspection?
To submit the activity for review, investigators must complete and submit the UC IRB
form “Determining Whether a Proposed Activity is Human Research According to DHHS
or FDA Regulatory Definitions” along with any other relevant information (e.g. grant,
protocol, data collection tools, letters of collaboration) required to evaluate the activity,
prior to initiation of the activity.
IRB protocols will be assigned to the specific IRB with the most expertise in that area.
The submission will be reviewed by the IRB Chair to determine if it contains enough
information to make a determination of whether the project requires an IRB protocol
(meets the federal definition of human subjects research). If not enough information is
provided, the chair will request additional information from the investigator.
Determinations will be made in accordance with DHHS (45CFR 46.102) and FDA
(21CFR50.3) regulations and applicable state and local laws. Each determination and the
basis of its decision will be documented. If the activity is determined to require review,
the Investigator will be informed in writing to submit the full protocol to the IRB for
review prior to initiating the activity. If the work is determined to not require review, the
Investigator will be notified in writing of the decision.
CONDUCTING HUMAN SUBJECTS RESEARCH WITHOUT IRB APPROVAL
It can be very difficult to determine what requires IRB review. In addition to clinical
research studies, regulatory requirements to protect human subjects apply to a much
broader range of research than many investigators realize, and researchers using human
specimens and/or data are often unsure about how regulations apply to their research.
Investigators are encouraged to contact the IRB office for guidance on determining if an
activity requires IRB approval.
If the IRB receives a protocol for review after a study has been completed, without prior
IRB approval, the protocol will not be reviewed. The Investigator will be notified of the
regulatory requirements requiring prospective IRB review and approval of human
subjects research. The Investigator will be informed that the data may not be used for any
publications, presentations, thesis, or dissertation requirements. The unapproved human
subjects research activity will be investigated as described in Policy VII.03
“INVESTIGATING ALLEGATIONS OF NON-COMPLIANCE IN HUMAN
SUBJECTS RESEARCH” and appropriate actions will be taken.
Examples of Human Subjects Research:
1. Clinically oriented research.
a. Mechanisms of human disease
b. Therapeutic interventions
c. Clinical trials
d. Development of new technologies
e. Research using human specimens and/or data including
i. Bodily materials, such as cells, blood or urine, tissues, organs, hair
or nail clippings, from living individuals who are individually
identifiable to the investigator(s), even if these materials were
collected by others;
ii. Residual diagnostic specimens from living individuals that are
individually identifiable to the investigator(s), including specimens
obtained for routine patient care that would have been discarded if
not used for research;
iii. Private information, such as medical information, about living
individuals that is individually identifiable to the investigator(s),
even if the information was not specifically collected for the study
in question. This category includes retrospective chart reviews
2. Epidemiologic and behavioral studies that generate data by means of
questionnaires, observation, studies of existing records, and experimental designs
involving exposure to some type of stimulus or intervention
3. Outcomes research and health services research studies designed to measure the
outcome of medical treatment
The IRB shall use the following definitions to determine whether an activity shall qualify
as human subjects’ research requiring IRB review and approval:
1. “Human Subjects Research” is federally defined and includes all activities which
a. Meet the Department of Health and Human Services’ definition of ‘research’ as
any ‘systematic investigation, including research development, testing, and
evaluation, designed to develop or contribute to generalizable knowledge’ (45
CFR § 164.501); and which involve person(s) who qualify as ‘human subjects’
within the meaning of relevant regulations of the US Food and Drug
Administration as any ‘living individual about whom an investigator conducting
(i) Data through intervention or interaction with the individual, or
(ii) Identifiable private information or data from which the identity of the
subject is or may readily be ascertained by the investigator (45 CFR
b. Qualify under the Food and Drug Administration regulations as an
‘Investigational use" involving any use of an approved product in the context of a
clinical study protocol (21 CFR 312.3(b)) and which involves one or more
“human subjects” as defined in relevant regulations as individual(s) who are or
become participant(s) in research, either as recipient(s) of a test article or as a
control. A subject may be either a healthy human or a patient (21 CFR 56.102(e);
c. Research activities subject to this policy shall include clinical investigations
regulated by the Food and Drug Administration under sections 45 CFR 505(i) and
520(g), including any use of a drug, other than the use of an approved drug in the
course of medical practice, and clinical investigations regulated by the Food and
Drug Administration under section 45 CFR 520(g), including any use of a
medical device, other than the use of an approved medical device in the course of
2. “Systematic Investigation” typically involves a predetermined method for studying a
specific topic, answering a specific question(s), testing a specific hypothesis(es), or
Examples: observational studies, interview or survey studies, group comparison studies,
program evaluation, test development, interventional research.
3. “Clinical investigation” means any experiment that involves a test article and one or
more human subjects,
4. “Designed to contribute to generalizable knowledge” typically requires that results
(or conclusions) of the activity are intended to be extended beyond a single individual or
an internal program.
Examples: Activities where there is an intent to publish the results in a peer-reviewed
journal or to present at a regional or national meeting, as well as, theses or dissertation
projects conducted to meet the requirements of a graduate degree.
5. “Individual” is a person who is or becomes a participant in research, either as a
recipient of the test article or as a control. The individual may be either a healthy person
or a patient
6. “Intervention” includes both physical procedures (e.g. venipuncture) and
manipulations of the living individuals or the living individuals' environments.
7. “Interaction” includes communication or interpersonal contact between the
investigator (or research team) and the living individual.
Examples: interviews, questionnaires, surveys, observations, manipulation of subject
behavior, diet, or environment, physical measurements, specimen collection (e.g. blood
tissue), administration of experimental drugs or devices.
8. Information is considered “Identifiable” if (1) the identity of the individual from
whom the information was obtained is ascertained or may be readily ascertained by the
investigator; or (2) the identify of the individual from whom the information was
obtained is associated or may be readily associated with the information.
9. “Private information” includes information about behavior that occurs in a context in
which the individual can reasonably expect that no observation or recording is taking
place or information that has been provided for specific purposes that the individual can
reasonably expect will not be made public (e.g., medical record, employee or student
Examples of individual identifiers include the subject's name, address, phone number,
social security number, medical record number, student or employee identification
number, or in some cases, the combination of data such that they can identify a single
individual through deductive reasoning. For example, data about employer, job title, age
and gender may not individually identify a subject, but when combined, could in certain
cases, identify a specific individual.
If the information cannot be linked to a living individual, or is considered public or is
given with the expectation that it will be made public and that it will be linked to the
individual (e.g. biography, news story), then it would not be considered private
identifiable information. For example, use of a publicly available data set that does not
contain any identifiers or codes linked to individuals does not involve human subjects
research. However, use of a publicly available data set that does contain identifiers or
codes linked to individuals does involve human subjects research (that would be
• 45 CFR §46.101(a), 45 CFR §46.102(d), 45 CFR §46.102(f), 45 CFR §46.102(f)(1), 45
CFR §46.102(f)(2), 21 CFR §50.1, 21 CFR §50.3(a), 21 CFR §50.3(c), 21 CFR
§50.3(g), 21 CFR §50.3(j), 21 CFR §56.101, 21 CFR §56.102(c), 21 CFR §56.102(l)
Institutional Review Board (IRB)
UC has 2 medical boards
And 1 social/behavioral board
The University of Cincinnati has established three Institutional Review Board (“IRB”)
panels to review all proposed research involving human subjects to ensure that the rights
and welfare of participants in research are adequately protected.
The University of Cincinnati IRB serves as the IRB of record for the
• University of Cincinnati
• The Shriners’ Institute for Burned Children
• The Cincinnati Veterans Affairs Medical Center
The IRBs are composed primarily of faculty members from disciplines in which research
involving human subjects is integral to that discipline's work, as well as several members
from the community whose primary interest is in non-scientific areas. The Board(s)
membership, policies, and procedures are governed by an Assurance agreement with the
UC now has signed a Memorandum of Understanding with Cincinnati Children’s
Hospital which allows for acceptance of reciprocal review and approval. For more
information regarding conducting research at both institutions or involving children as
subjects, contact the IRB office at UC (558-5259) or CCHMC (636-8039) to help in
determining which institution should be the IRB of Record.
NOTE: Studies involving transfer of recombinant nucleic acids into humans (human
gene transfer) also require review and approval by the Institutional Biosafety Approval
prior to initiation.
To submit a protocol for IRB review:
SUBMITTING NEW PROTOCOLS
• Determining Human Research Activities
• Policy, see attached
• Form, see attached
• Medical Submission Packet , available from website
• Social/Behavioral Submission Packet, available from website
• The medical IRB boards meet weekly, on Wednesdays
• Social/behavioral board meets once a month on the third Thursday
• The IRBs encourages you to submit as soon as your application is completed.
• Incomplete applications will be returned.
• If the IRB determines that your study meets federal criteria for Expedited review,
then review will be independent of IRB meeting dates. Submissions are sent directly
to the chair or IRB members (social/behavioral) for review. All comments, questions,
and responses will handled by email.
• The IRB determines that you study requires Full-Board review, the following
scheme illustrates the process.
IRB Office Reviews
6 3 1 New Protocols (1-6)
5 Modifications (1-6)
4 Progress Reports (1, 4-5-6)
IRB Approval Meeting 2 Route to Review Committee
3 Reviewers Comments
4 IRB Meeting Approval Process
5 IRB Office Processing
6 IRB Office Approval Notification
7 Adverse Events (7)
If all forms and documents are correctly submitted, the average
time from submission to final approval is from 6-8 weeks. This
time can be significantly delayed if the required responses from
the Principal Investigator or their contact person are not
addressed in a timely fashion.
• The Federal Government (DHHS 45 CFR 46) and The University of Cincinnati
require that you demonstrate your knowledge of basic ethics and Human Subjects
• The IRB site contains information on the IRB Committees, the IRB Office, and
the protocol process. http://researchcompliance.uc.edu/irb/default.html
• You will find information on HIPAA waivers, forms, orientation procedures,
regulations, and FAQs.
Online training is available:
• CITI Human Research Protection Online (Using the 'Greater Cincinnati
Academic and Regional Health Centers' Meets UC’s HRP training
• Training HRP Instructions
51 Goodman Ave, Suite 300
Telephone: (513) 558-5259
Fax: (513) 558-4111
Institutional Review Board Office
51 Goodman Avenue, Suite 300, ML 0567
University of Cincinnati Medical Center
PO Box 670567
Cincinnati, OH 45221-0567
General Inquiries: 558-5259
Training and Education:
Claudia Norman, 558-5784 (firstname.lastname@example.org)
New Protocols & Pre-approval,
Katie Krier: 558-5136 (Katie.Krier@uc.edu)
Jo Ann Behrle: 558-5273 (Joann.email@example.com)
Tara Knipp: 558-3731 (Tara.Knipp@uc.edu)
Progress Reports: Laura Goins, 558-0479 (Laura.Goins@uc.edu)
Martina Harmon, 558-1881 (Martina.Harmon@uc.edu)
Carolyn West, 558-7580 (Carolyn.West@uc.edu)
Adverse Event Reports: Denise Washington, 558-7324
Justin Osborne, 558-2087 (Justin. Osborne@uc.edu)
Deborah Quinones-Stewart, 558-6915 (Deborah.Quinones-
External IRB Submissions:
Justin Osborne, 558-2087 (firstname.lastname@example.org)
Post-Approval Monitoring (Quality Assurance/Quality Improvement)
The Human Subjects Research Post-Approval Monitoring Program administers quality
assurance/quality improvement monitoring. Prior to monitoring, there was no quality-
assurance assessment of the actual research performance of individual study groups. The
post-approval monitoring program’s goal is to improve the quality of research throughout
the institution. “Any study which is approved by the IRB or conducted by UC affiliated
investigators may be monitored.”
The purpose of this program is to ensure that scientific, ethical and regulatory
requirements are followed in all Institutional Review Board approved protocols.
The program is also designed to improve the quality of research by detecting errors
and/or omissions that might occur when performing research activities.
This will also give the investigators an opportunity to ask questions and receive
information about regulations and issues regarding the protection of human subjects.
Daniel Woo, MD
Post Approval Monitoring Program
Fax: 513. 558.5478
Angela Braggs-Brown, RAC
Type of Materials Monitored
• Education of investigators
o Are all investigators up-to-date on training requirements?
o What other education is taken?
• Informed consent observations
o Is the manner of obtaining informed consent in a non-coercive manner?
• Performance of the study
o Does the study follow the study protocol?
o Is there a screening and exclusion log?
o Are there procedures in place to protect vulnerable populations including
pregnant women, children and prisoners?
• Adverse Events & communications from subjects
o Is reporting to the IRB including protocol violations and Adverse Events
timely and accurate?
• Data & tissue handling
o Are laboratories certified and tissue handling performed appropriately?
• Drug/device storage
• Are all regulatory documents maintained?
• Are all required submissions to FDA documented?
• Are all case report forms completed and verifiable by primary source documents?
There are two processes:
1. Off-site review (self assessment)
• complete questionnaire
• recommendations to self-assessment responses sent to IRB Chair
2. On-site review
• Formal visit by Post Approval Monitor
• Interview of Principal Investigator
• Review of study documents, SOPs, etc.
• Observation of consent process
• Medical Director will meet with PI for interview
• Final report sent to Compliance Officer and IRB Chair
Regulatory Mandates http://researchcompliance.uc.edu/PAM/RegulatoryMandates.html
The Human Subject Research Post-Approval Monitoring is governed by the
• The Belmont Report
• Code of Federal Regulations (CFR) governing human research
• FDA 21 CFR 50 (Protection of Human Subjects)
• FDA 21 CFR 54 (Financial Disclosure by Clinical Investigators)
• FDA 21 CFR 56 (Institutional Review Boards)
• FDA 21 CFR 312 (Investigational New Drug Application)
• FDA 21 CFR 812 (Investigational Device Exemptions)
• DHHS 45 CFR 46 (The Common Rule )
• DHHS 45 CFR 164 (Health Insurance Portability and Accountability Act of 1996)
• FDA Information Sheets
• ICH Good Clinical Practice (GCP) Guidelines
SOPs for GCP are Available for download and modification for individual
investigator use from the ORCRA Website
Some Frequently Asked Questions associated with monitoring:
IND/IDE Assistance Program
Angela Braggs-Brown, RAC
What is a FDA warning letter?
As part of the Food and Drug Administration (FDA) Bioresearch Monitoring Program,
the FDA routinely conducts clinical study- oriented inspections of high enrollment
clinical sites used in support of New Drug or new device applications. These inspections
are designed to validate clinical studies on which final approval maybe based and to
assure that the rights and welfare of the human subjects in those studies are protected.
The first notice of the FDA’s concern is usually the FDA483 issued during the
inspection. A lack of an adequate response to the 483 could result in the issuance of a
A WARNING LETTER is a serious notice to an investigator and demands development
of effective corrective actions, with the threat of legal penalties if the actions are not
impending. Serious repeat violators may be banned by the FDA from performing clinical
research on FDA-regulated products. Additionally, the data from any clinical
investigator’s site could be rejected from consideration in the FDA submission it is
intended to support.
Between September of 2006 and January of 2007, the University of Cincinnati received 3
warning letter from the FDA regarding "objectionable conditions" and non compliance
with Federal Regulations 21 CFR §812, regarding INDs.
As part of the Corrective Action Plan required by the FDA, ORCRA is undertaking pre-
review of ALL protocols submitted to the IRB that involve an IND or IDE held by
The current version of Human Research Protection Program Policy III.08: Review of
sponsor-investigator investigational new drug (IND)/investigational device exemption
(IDE) research in human subjects research is available on the IRB website
The FDA considers those documents that individually and collectively permit evaluation
of the conduct of a clinical trial and the quality of the data produced to be essential. These
documents serve to demonstrate the compliance of the Sponsor-Investigator with the
standards of Good Clinical Practice (GCP) and will meet all applicable regulatory
requirements and ICH E6 guidelines.
All essential documents must be maintained
The following documents are essential documents:
IRB, FDA, and other regulatory documents (e.g. reports, letter of
Consent form and IRB-approved information for subjects
Sample CRF or document stating medical record is data collection
Investigator and sub-investigators CV or documentation regarding
qualifications and training
Site signature sheet
Lab normal ranges
Adverse event log
Subject code list
Product accountability log (IDS or registry)
Product handling and storage instructions
Product shipping records and certificates of analysis
Record of retained samples
Decoding procedures for blinded trials
Record retention plan
Compiling an IND Annual Report
Information needed to meet the requirements of compiling an IND Annual report
submitted to the FDA (FDA Annual Reports 312.33). A sponsor shall within 60 days of
the anniversary date that the IND went into effect (i.e., the date the FDA permitted the
study to begin) submit a brief report of the progress of the investigation.
Individual study information
• A brief summary of the status of the study during the previous year. It must
o Study title, its purpose, statement identifying the patient population,
whether the study is completed.
o Total number of subjects planned for inclusion; number entered to date
tabulated by age, gender, and race; number of subjects who completed the
study; number of subjects who dropped out of the study for any reason.
o A brief description of any available study results.
• A narrative or tabular summary showing the most frequent and most serious
adverse events by body system.
• A summary of all IND safety reports submitted during the past year.
• A list of all subjects who died during participation with the cause of death.
• A list of subjects who dropped out because of an adverse experience, whether or
not thought to be drug related.
• A brief description of information that was learned regarding the drug s actions
(e.g., dose response, bioavailability).
• (If applicable) A list of preclinical studies (including animal studies) completed or
in progress during the past year and a summary of the major findings.
• (If applicable) A summary of any significant manufacturing or microbiological
changes made during the past year.
General investigational plan
A description of the general investigational plan for the coming year. It should include:
rationale; indications; general approach in evaluating the drug; clinical trials to be
conducted; estimated number of patients; and risks.
A statement that an investigator brochure is not required for an investigator sponsored
A description of any significant protocol modifications made during the previous year
and not previously reported to the IND in a protocol amendment.
21 CFR 312 Requirements for Investigational New Drug Application
Bioresearch Monitoring Information System File: Clinical Investigators, CROs and IRBs
from FDA 1571 & 1572s
Center for Drug Evaluation and Research (CDER)
FDA integrity program
CDRH Bioresearch Monitoring
CDRH Device Advice
Electronic Regulatory Submissions and Review
Harvey M. Arbit, Investigator-initiated Research: the IND and IDE Process, SoCRA
Source, 15, August 2007 (Pdf)
What to Expect and How to Handle an FDA Inspection, Joseph X. Kaufman, Community
Research, UC Presentation, July 20, 2007 (Ppt)
Guidelines for Monitoring Clinical Investigations (FDA) (Pdf)
E6 GCP for Industry (Pdf)
Information Sheet Guidance for IRBs, Clinical Investigators and Sponsors
• Significant and Nonsignificant Risk Medical Device Studies (Pdf)
• FDA Inspections of Clinical Investigators (Pdf)
Clinical Monitoring guidance for Sponsor Investigators (Pdf)
IND/IDE Checklist (Excel spreadsheet)
Sponsor-Investigator Roles and Responsibilities
IND/IDE Symposium Presentations (Ppt), Nov 16, 2007
• The Investigator as a Sponsor: Rewards and Pitfalls, Jane A. Green, PhD
• The Difference between Practice and Research – What the FDA Expects You to
Understand, Harvey M. Arbit, PharmD, MBA, RAC
Vertebrate Animal Research
Institutional Animal Care and Use Committee
Laboratory Animal Medicine Services
Housing Space Needs
Veterinary Health Issues
IACUC is the Institutional Animal Care and Use Committee
The IACUC is federally mandated by both USDA Animal Welfare Act Regulations
(AWARs) and the Public Health Service Policy on Humane Care and Use of Laboratory
Animals (PHS policy). The IACUC responsibilities are to oversee and evaluate the
institution’s animal program, procedures, and facilities to ensure they are consistent with
the recommendations in the Guide for the Care and Use of Laboratory Animals (the
Guide), the AWARs, and the PHS Policy.
Essentially, the IACUC serve as animal research ethics board committed to the welfare
of animals. The IACUC plays an important role in ensuring that the animals under its
purview are used and cared for in a humane manner.
The university is committed to the quality of its animal care and use program and
participates in voluntary peer reviewed accreditation program with the Association for
the Assessment and Accreditation of Laboratory Animal Care (AAALAC) International.
Regulatory Charges of the IACUC
• Review the institution’s program for animal care and use at least biannually
• Inspect all the institution’s animal facilities, including animal study areas and
• Report to the Institutional Official on the above inspections and reviews and make
recommendations for corrections
• Investigate concerns involving the care and use of animals at the institution
resulting from complaints from personnel at the institution or the public
• Review proposed activities related to the care and use of animals including
modifications to previously approved activities (protocol review).
• Suspend an activity involving animals if it does not comply with PHS policy,
AWRs, the Guide, or the University of Cincinnati’s Animal Welfare Assurance.
To submit an Animal Use Protocol:
• Download the protocol template from the IACUC website
• Review hints and tips on the download page
• If questions arise with completing the template, please call Rob Anderson at 558-
• Email a draft protocol to Rob.Anderson@uc.edu
• The IACUC Office will contact you to schedule a Preliminary Review Meeting
Investigator IACUC Office IACUC
1 2, 5
4, 8 3 Safety
IACUC Approval Meeting
(FULL REVIEW PROTOCOLS ONLY)
1) PI Submits Protocol Template to IACUC Office
Pre-Review: IACUC Office Staff + Veterinarian meet with the PI to Pre-
Reviews the protocol prior to submission to the IACUC
2) IACUC Office routes protocol to IACUC Reviewers & Safety Offices
Designated Review: 2 Members + Veterinarian (no meeting approval
Full Review: All members (meeting approval required)
3) Reviewers return comments to IACUC Office
4) IACUC Reviewer Comments Routed to PI
5) PI response to Reviewer comments routed to reviewing IACUC members
6) IACUC Full Review at Convened Meeting
7) Committee Decision Routed by IACUC Office
8) Protocol Approval Notification
Designated Review Approval: 2 Members + Veterinarian may approve
Full Review Approval: Requires majority vote at convened meeting for
Safety Approval: IACUC approval is contingent upon (bio)safety approval
Local policies on the use of animals in research
IACUC Policies can be found at: http://researchcompliance.uc.edu/iacuc/Policies1.html
IACUC Training requirements can be found at:
• Both OLAW and the USDA require proper training of all personnel who will
work with vertebrate animals. At the University of Cincinnati and Shriner’s
Hospitals for Children, all personnel must attend Orientation prior to working
with animals and every 3 years thereafter. Orientation sessions are provided on a
regular basis. As research staff is added to protocols, their experience is reviewed,
and they must attend appropriate training before beginning work with animals.
• Registration for training should be sent to: IACUC.Training@uc.edu.
• For questions about required training call (513)558-5187.
• A Certification Examination is conducted at the end of Orientation. All personnel
must receive a passing score to receive credit for the Orientation. If a passing
score is not received, personnel will be required to attend another Orientation
• The Principal Investigator (PI) must complete IACUC Orientation and other
applicable training before the IACUC will consider approving the protocol. If
funds need to be transferred from another institution and the PI is not yet at UC,
the protocol may be approved but animals cannot be ordered and animal studies
may not begin until all training requirements have been met. The approval will be
valid for 60 days.
Frequently Asked Questions and answers can be found at:
Report concerns for animal misuse or abuse:
• IACUC Office 559-5187
• Compliance Hotline 1-800-889-1547
• LAMS Veterinary Staff 558-5171
IACUC Office Contacts
Rob Anderson, Director IACUC
George Babcock, Chair IACUC
Kareemah Mills, Protocol Program Manager
Sandra Rebholz, Program Director - Compliance
David Custer, Program Manager - Training
Laboratory Animal Medicine Services (LAMS)
The primary mission of Laboratory Animal Medical Services is to provide an animal care
and use program for the University of Cincinnati research and teaching community. This
program provides for the health, husbandry and veterinary medical care of animals under
the University of Cincinnati's stewardship. The department delivers such are in a
compassionate, humane and respectful manner, as well as maintaining the highest
standards of quality and strives to achieve accreditation and compliance excellence.
Laboratory Animal Medical Services serves as a resource to the medical research
community through the provision of education, training and consultative services and
provides leadership and direction in response to scientific advancements.
To Order Animals from LAMS http://medcenter.uc.edu/lams/lamspp.html#areq
REQUISITIONS-Animal SOP Information for the Researcher:
1. Complete the Animal Acquisition Training (online).
2. Complete the Animal Requisition Form thoroughly.
3. Make sure you have completely filled out the form and that your Business
Manager has signed the form or it will be returned unprocessed.
4. There is a $42.98 fee per order
Late Fees are $15.00 each
5. Animal Requisitions must be submitted by NOON on Wednesday
6. Late Fees will incur if forms are submitted after NOON on Wednesdays through
NOON on Thursdays
SOPs for Animal Housing can be found at: http://medcenter.uc.edu/lams/usda.html
Douglas Stone, DVM Director LAMS
Dale Goss, Assoc. Director – Husbandry
Vicki Shaw, Business Administrator
BIOSAFETY OFFICE: 513-558-6182 or 513-558-5210
51 Goodman Avenue, University Hall Suite 300
Cincinnati, Ohio 45221
Mail Location: 0767
Marcia Espinola, DVM, MS, CBSP
Director Biological Safety Office
Biological Safety Officer
Erin L. Dunn
Biological Safety Specialist & IBC Administrator
Gary E. Dean, PhD
IBC Chairman and BSL3 Facility Director
The Biosafety Program
The goal of the Biological Safety Program is to ensure compliance with all institutional
requirements and all federal, state, and local regulations pertaining to the possession, use,
storage and transfer of biohazardous agents, as well as ensuring the safety of university
employees and the surrounding community.
Components of the Biosafety Program
The University of Cincinnati Biosafety Program has two functional components:
• The Biosafety Office
• The Institutional Biosafety Committee (IBC).
The Biosafety Office is charged with ensuring compliance with institutional
requirements and federal, state and local regulations pertaining to the possession, use, and
transfer of biohazardous agents. In addition, the Biosafety Office, under the direction of
the Biosafety Officer (BSO), is responsible for performing risk assessments to identify
hazards and to guide Principal Investigators and staff in implementing practices and
procedures that will minimize or eliminate risks associated with research involving
The Institutional Biosafety Committee (IBC) is charged by the Senior Vice President
and Provost for Health Affairs to review and approve all University research activities
involving the use of biohazardous (or potentially biohazardous) agents and recombinant
DNA molecules, as described in the National Institutes for Health “Guidelines for
Research Involving the Use of Recombinant DNA Molecules” (NIH Guidelines,
http://oba.od.nih.gov/rdna/nih_guidelines_oba.html and the current edition of the
Centers for Disease Control and Prevention’s “Biohazards in Microbiological and
Biomedical Laboratories” (the BMBL or “CDC Guidelines”
http://www.cdc.gov/OD/ohs/biosfty/bmbl5/bmbl5toc.htm .The administrative support
for the IBC is provide by the IBC office (Biosafety Office and IBC chairman).
• Biosafety Frequently Asked Questions and their answers can be found at:
Agents regulated by the IBC
The IBC reviews all research protocols involving:
• Recombinant DNA
• Agents infectious to humans, animals, or plants
• Human derived materials
• Trans-activating proteins
• Genetically altered agents or organisms
• Biological toxins (regulated amounts)
• Dual Use Agents
• Transgenic (genetically modified) animals
Basis for the Classification of Biological Agents by Risk Group (RG)
Risk Group 1 (RG1) Agents that are not associated with disease in healthy adult humans
Risk Group 2 (RG2) Agents that are associated with human disease which is rarely
serious and for which preventive or therapeutic interventions are often available
Risk Group 3 (RG3) Agents that are associated with serious or lethal human disease for
which preventive or therapeutic interventions may be available (high individual risk but
low community risk)
Risk Group 4 (RG4) Agents that are likely to cause serious or lethal human disease for
which preventive or therapeutic interventions are not usually available (high individual
risk and high community risk)
Risk assessment is ultimately a subjective process. The investigator must make an initial
risk assessment based on the Risk Group (RG) of an agent. In deciding on the appropriate
containment for an experiment, the initial risk assessment should be followed by a
thorough consideration of the agent itself and how it is to be manipulated.
Factors to be considered in determining the level of containment include agent factors
such as: virulence, pathogenicity, infectious dose, environmental stability, route of
spread, communicability, experimental procedures, quantity, availability of vaccine or
treatment, and gene product effects such as toxicity, physiological activity, and
Relationship of Risk Groups to Biosafety Levels
Risk Biosafety Level Laboratory Type Laboratory Safety Equipment
1 1 Basic Teaching, GMT
None; Open bench work
2 2 Primary health GMT plus personal
services, protective Open bench plus BSC for
diagnostic equipment, potential aerosols
services, research biohazard sign
3 3 Special diagnostic BL2 plus special
BSC and/or other primary
services, research clothing,
containment devices for all
4 4 Dangerous BL3 plus airlock
Class III BSC, positive
pathogen units entry, shower exit,
pressure air suits, double
ended autoclave, filtered air
Work with RG4 agents Is NOT permitted at UC
GMT – Good microbiological technique, BSC – Biological Safety Cabinet
*Note*: Risk groups & Biosafety Levels are two separate rankings and in rare instances
may differ in number, subject to consideration by the IBC.
On June 12, 2002 President Bush signed the “Public Health Security and bioterrorism
Preparedness and Response Act of 2002” (Public Law 107-188
The Law's purpose is to improve the ability of the United States to prevent, prepare for,
and respond to bioterrorism and other public health emergencies. The Law requires that
all persons possessing select biological agents or toxins (http://www.cdc.gov/od/sap/ )
deemed a threat to public health, animal or plant health, or animal or plant products
register with the appropriate federal agency.
On March 18, 2005, final rules were published in the Federal Register by the
Departments of Health and Human Services (HHS) and Agriculture (USDA) governing
facilities that possess, use or transfer select biological agents or toxins. These rules
became effective on April 18, 2005.
Requirements to work with select agents
Individuals who intend to possess, use or transfer select agents must be approved by the
USDA/CDC as part of the University of Cincinnati’s registration for the access to select
agents and toxins under the conditions specified in the entity registration, in accordance
with 42 CFR part 73, 9 CFR part 121 and 7 CFR part 331.
BE AWARE: Individuals may not self register.
The registration process is conducted through the Biosafety Office (BSOf)
Approval of individual registrations may take from 3 to 6 months.
To begin the process for approval, the individual PI, and any laboratory personnel who
will have access to select agents, will need to obtain security clearance (Security Risk
Assessme nt – SRA) by the United States Department of Justice, Federal Bureau of
Investigations, Criminal Justice Information Services. In order to obtain the SRA
• Contact the BSOf.
• The BSOf will complete the registration forms to obtain the unique identification
number from the USDA. If individual is a PI, details of research and agents must
• The BSOf will provide the form FD-961 for the SRA. Complete form returns to
• Once the USDA/APHIS assigns the unique identification number, individual will
be instructed to contact the UC Police Department for fingerprinting.
In addition to obtaining approval for possession, use and transfer of select agents and
toxins by the USDA/CDC, the PI will be required to comply with all institutional
requirements involving the use of biohazardous agents and recombinant DNA molecules
which includes approval by the Institutional Biosafety Committee. completion of all
required BSL3 training and approval to work in the BSL3 facility. Please note the
• Approval for the possession, use and transfer of select agents and toxins cannot be
transferred from one entity to another.
• Approval for the possession, use and transfer of select agents and toxins is required, as
part of UC’s entity registration, by all personnel who will have access to these agents at the
University of Cincinnati, including UC faculty ,research personnel and visiting scientists.
NIH Guidelines for Research Involving Recombinant DNA
Institutional Biosafety Committee (IBC) Approval of Research Using Recombinant
DNA is Federally Mandated
The NIH and the University of Cincinnati require research involving recombinant DNA
to be reviewed and approved by the IBC.
Non-compliance with the NIH Guidelines places not only individual funding, but all
research funding at UC in jeopardy.
The University of Cincinnati IBC must also review and approve all research involving
biohazardous agents (e.g. bacteria, viruses, fungi, protozoa, prions) and / or human source
materials (e.g. blood, bodily secretions and tissues, primary and established cell lines).
Submitting an IBC Protocol:
The first step to submitting an IBC protocol is to contact the Biosafety Office to obtain
access to the protocol submission website.
• The Biosafety Office is available to assist you with completion of your IBC
Regulations and Mandates
Recombinant DNA and Biohazards:
• The National Institutes of Health Recombinant DNA Guidelines: “NIH
Guidelines for Research Involving Recombinant DNA Molecules” (NIH
• CDC/ NIH biosafety guideline, “Biosafety in Microbiological and biomedical
Laboratories (BMBL) 5th Edition.
• CDC Select Agent Program
• USDA Select Agent Program
• CDC/USDA Select Agent Exemptions
• The USA Patriot Act
• Public Health Security and bioterrorism Preparedness and Response Act, 2002
The Department of Transportation, 49 CFR, Regulations on the Interstate
Shipment of Hazardous Materials
• The International Air Transportation Association Guidelines on the Shipment
of Infectious and Diagnostic Specimens (only available in print)
Refer to the University of Cincinnati Environmental Health and Safety Department for
information on hazards associated with laboratory chemicals and procedures. You may
also refer to the Occupational Health & Safety Administration website for applicable
• OSHA Bloodborne Pathogen Standard
• OSHA Hazard Communication Standard
• OSHA Lab Standard
Technician on Call:
Page at 249-6812
University of Cincinnati
Radiation Safety Office
PO Box 670591
Radiation Safety Laboratory
170 Panceza way
PO Box 670591
Cincinnati, OH 45267-0591
Telephone: (513) 558-4110
Fax: (513) 558-9905
Radiation Safety Officer
Victoria Morris, MS, CHP
Radiation Control and Safety Program
The Radiation Control and Safety Program (RCSP) is overseen by
• The Radiation Safety Committee (RSC)
• The Radiation Safety Officer (RSO)
The RSC and RSO work in tandem to ensure the health and safety of personnel, along
with ensuring compliance with applicable rules, regulations and license conditions.
Duties of the Radiation Safety Committee
The RSC is a committee of the Office of the President.
• The RSC is responsible for generating, defining, implementing and monitoring a
RCSP that complies with rules, regulations and license conditions.
• The RSC grants and withdraws authorized user (AU) status and restricts radiation
source usage as needed for safety and compliance.
Responsibilities of the Radiation Safety Officer
• The RSO is responsible for implementing the RCSP and ensuring for UC that
radiation safety activities are in accordance with rules, regulations and license
• The RSO, with the assistance of Radiation Safety Office (RSOf) staff, is
responsible for managing the day-to-day operations of the RCSP.
Radiation Safety Office
The mission of the University of Cincinnati Radiation Safety Office is to provide the
means necessary for personnel to protect themselves, their coworkers, the general public,
and the environment from detrimental effects of radioactive materials and radiation
generating equipment used under the University's Radiation Control and Safety Program.
Its mission is also to provide day- to-day oversite and services to meet the goals of the
Radiation Control and Safety Program.
Training in Radiation Safety is a Requirement
RAM Radiation Worker Training Schedule
(for individuals who may handle radioactive materials in a research or clinical setting)
SEE WEBSITE FOR TRAINING SCHEDULES
Contact the Radiation Safety Office at 558-4110 to schedule a training session.
Information Available on the Radiation Safety Website
• Manuals, QMP & Policies
• Isotope Fact Sheets
• Isotope vendors
• Training schedule
• Chart of nuclides and decay calculator
• Request special survey or waste pickup
Newsletters are issued quarterly to all authorized users. Copies are maintained on
the Radiation Safety website.
Frequently Asked Questions and answers can be found at:
Training Opportunities on the ORCRA Website
This site is your gateway to online compliance training, online competency testing, non-
online educational programs and compliance training-related news
• CITI Human Research Protection Online
• Training HRP Instructions
• Continuous Professional Development (CPD) online compliance training
• Blood Borne Pathogens
• Radiation Safety
• UC Physicians
• GCP Training
• Self Paced Training
• Continuous Professional Development (CPD) online compliance training
• Biomedical Research HRP Knowledge Exam
• IRB-M HRP Knowledge Exam
• IRB-S HRP Knowledge Exam
• Social and Behavioral HRP Knowledge Exam
Educational Programs News and Announcements
• Hot Topics Schedule New Policy: Demonstrating
• Investigator 101 of Human research Protection by
• IRB Seminar Researchers
• Orientation Program
• Research Education Advisory Committee Training Instructions
• FAQs (frequently asked questions)
Information on Drug Licenses
Ohio law requires investigators to hold a DEA license for any and all drugs used in
all basic research.
For the Ohio State Board of Pharmacy application, there is a different fee associated with
each “Schedule” of drug you are using. This fee should accompany your OSBP
application to Columbus
Information Regarding Fees and Exemption:
For the DEA application, there is a section that requests “PERSON CERTIFYING
EXEMPTION”. Since UC is a state agency, the fee is waived for the DEA license. In
this section, insert “Fred Hamilton, Assoc General Counsel” as this person. Insert his
phone number as (513) 558-7748” also.
United States Drug Enforcement Agency FAQs
Drug Enforcement Agency Ohio State Board of Pharmacy Slideshow
Ohio State Board of Pharmacy Rules Regarding Laboratories
Usage and Inventory Log
To Report Any Compliance Concerns:
Toll-free Anonymous Compliance Hotline 1-800-889-1547 or anonymous email at
Any concerns of University employees concerning the human research protection
program should be shared with the appropriate academic or administrative manager for
action. Employees who have concerns about job security arising from reporting internally
may use the University’s toll-free reporting hotline. The hotline is free to the user, and
anonymous. Callers may report noncompliance and request a copy of the final report.
Although the caller’s name and mailing address may be given to the compliance agency,
no one at the University may access this information. The caller remains 100%
anonymous to all individuals at the University! It should be noted that this hotline could
be used to report any compliance concerns at The University of Cincinnati.
The hotline is not restricted to research concerns