Office of Research Compliance and Regulatory Affairs *ORCRA*

1. Research Orientation Office of Research Compliance and Regulatory Affairs*ORCRA* What you need to know about Research Compliance at UC December 7/14, 2007 Melissa Colbert, PhD Director, ORCRA Research Compliance Officer

2. Mission Statement 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 radioactivity 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 possible. Research Compliance Officer: Melissa C. Colbert, PhD Director ORCRA 3223 Eden Avenue Room G-013, ML0567 Cincinnati, OH 45267-0567 513.558.5034 Melissa.colbert@uc.edu Research.compliance@uc/org

3. What is ORCRA? The Office of Research Compliance and Regulatory Affairs covers: • Human subject protection – IRB • Post IRB approval monitoring • Animal welfare & protection – IACUC • Biohazard use – IBC & IBCOf • Radiation safety – RSOf & RSC • FDA Assistance*

4. ORCRA’s Website http://researchcompliance.uc.edu/

5. ORCRA Newsletter • October 2007 • We appreciate the enthusiastic response we received after the first Compliance Matters hit inboxes. The second issue of Compliance Matters is coming to you with an added section under IRB News. Our recent accreditation by the Association for the Accreditation of Human Research Protection Programs (AAHRPP) reminded us of the importance of communicating updates to policies and procedures to the entire research community. Each issue wiII include a listing of any updates we’ve made, along with links to the full policy and procedure revisions. • Read on to learn more about exciting new initiatives and educational opportunities, and don’t hesitate to let us know if we’re missing anything. You can contact us at research.compliance@uc.edu. For archived editions of Compliance Matters, additional information on ORCRA or to download related documents, visit researchcompliance.uc.edu. • Melissa Colbert, PhD • Director, Office of Research Compliance and Regulatory Affairs (ORCRA) • Research Compliance Officer • IN THIS ISSUE: • Spotlight on: The Transgenic Database • ORCRA News • IACUC News • IBC News • IRB News/New or Updated HRP Policies and Procedures • Quality Improvement Tips for Investigators • Radiation Safety News • Research Compliance Events and Training Opportunities

6. IRB Reviews & Approves 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/orcollect 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 met: • the research is sponsored by the University, or • the research is conducted by or under the direction of any University employee or agent of this institution in connection with his/her institutional responsibilities, or • the research is conducted by or under the direction of any University employee or 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

7. Human Subject Research is Federally Regulated • DHHS Office of Human Research Protection(45 CFR 46) • FDA (21 CFR 50 Human Subjects; 21 CFR 56 IRBs) • Association for Accreditation of Human Research Protection Programs, AAHRPP

8. UC is Fully Accredited • UC’s IRB has been accredited by AAHRPP • There are established policies and procedures governing all aspects of research involving human subjects. • These are available on http://researchcompliance.uc.edu/irb/default.html

9. RESEARCH, etc Education, Training & Consulting Documentation of Training is Required • The Federal Government (DHHS 45 CFR 46) and The University of Cincinnati require that you demonstrate your knowledge of basic ethics and Human Subjects Protection • This can be fulfilled by online training: • CITI Human Research Protection Online(Meets UC's HRP training requirement) • Training HRP Instructions • Additional individualized or group training to help with IRB submission is available through: Sponsored by the Office of Research Contact Dawn O’Neill for arrangements 558-6565

10. Forms for IRB Review are Available on the ORCRA Website http://researchcompliance.uc.edu/irb/default.html SUBMITTING NEW PROTOCOLS      • Determining Human Research Activities • Policy* • Form*  • Medical Submission Packet • Social/Behavioral Submission Packet IRB is moving toward electronic submission. eMODs will be the first piece and will be rolled out through Researcher’s Gateway in Jan 2008!

11. IRB Office Contact Information Location: G-08 Wherry Hall, ML 0567 Telephone: (513) 558-5259 Fax: (513) 558-4111 Mailing Address: Institutional Review Board Office                              G-08 Wherry Hall, ML 0567                              University of Cincinnati Medical Center                              PO Box 670567                              Cincinnati, OH 45267-0567

12. IRB Office Staff Contacts

13. ORCRA Provides Post Approval Monitoring The Human Subjects Research Post-Approval Monitoring Program administers quality assurance/quality improvement monitoring. 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 provides the investigators an opportunity to ask questions and receive information about regulations and issues regarding the protection of human subjects.

14. Criteria for Study Selection • All studies, including exempt research, are subject to quality monitoring • Emphasis on • Moderate to High Risk • Investigator initiated studies • Sponsor-investigator IND/IDE • Studies involving vulnerable populations • Potential conflict of interest • Those without external monitoring

15. Monitoring Process There are two processes: 1. Off-site review (self assessment) • complete questionnaire 2. On-site review • Formal visit by Program Director • Interview of personnel • Review of SOPs, etc. • Observation of consent process • Medical Director will meet with PI for interview • Final report sent to Compliance Officer, IRB Chair, & Senior VP for Research

16. No Formal Training is Required, But…. • While not mandatory, training in Good Clinical Practices (GCP) is strongly suggested. • Templates for SOPs for GCP are available at the FDA Assistance site of research compliance.

17. Contact Information Post Approval Monitoring Program Daniel Woo, MD Medical Director Phone: 513.558.2705 Fax: 513. 558.5478 ML: MSB 0525 email: daniel.woo@uc.edu Joanne A. Lindwall, Director Phone: 513.558.3576 Fax: 513.558.4498 ML HPB 0661 email: joanne.lindwall@uc.edu Angela Braggs-Brown Phone:513.558.3005 Fax: 513.558.4498 ML HPB 0661 Email: broag@uc.edu

18. Animal Research:IACUC & LAMS IACUC • Protocol Prep & Review • Personnel Training • Compliance Monitoring Laboratory Animal Medicine Services • Animal Ordering • Housing Space Needs • Veterinary Health Issues

19. IACUC Institutional Animal Care and Use Committee Both federal Animal Welfare Act Regulations(AWARs) and the Public Health Service Policy on Humane Care and Use of Laboratory Animals (PHS policy) require that the Chief Executive Officer or his/her designee appoint an Institutional Animal Care and Use Committee (IACUC). 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.

20. Regulatory Bodies for Animal Research PHS Office of Laboratory Animal Welfare (OLAW) is charged with implementing the Health Research Extension Act (HREA) of 1985, as well as any policies/regulations established by PHS to implement HERA The United States Department of Agriculture(USDA)Animal and Plant Health Inspection Service (APHIS) is charged with implementing the Animal Welfare Act. The USDA has done so through the Animal Welfare Act Regulations and the Animal Care Policy Manual. The Association for the Assessment and Accreditation of Laboratory Animal Care International(AAALAC) is a non-profit association that provides a voluntary accreditation program to institutions wishing to demonstrate the highest level of commitment to responsible care and use of animals.

21. IACUC Responsibilities • 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 satellite facilities • Report to the Institutional Official on the above inspections and reviews and make recommendations for corrections • Investigateconcerns 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.

22. To submit an Animal Use Protocol: • Download the protocol template from the IACUC website http://researchcompliance.uc.edu/iacuc/ProtocolSubmissions.html • Review hints and tips on the download page • If questions arise while completing the template, please call • Rob Anderson at 558-5187 • Email a draft to Rob.Anderson@uc.edu • Schedule a Preliminary Review Meeting

23. Training is Mandated 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. Orientation covers the following items: • Federal Regulations, including OLAW & USDA regulatory requirements • Institutional Policies • AAALAC & The Guide for the Care and Use of Laboratory Animals • AVMA Panel on Euthanasia • Animal Welfare • Humane practice of animal maintenance and procedures • Reduction, Replacement, & Refinement • IACUC & LAMS • Overview of the University’s Occupational Health & Safety Program, including zoonotic diseases • 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 session. 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.

24. Laboratory Animal Medicine Services 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 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.

25. To report concerns of animal misuse or abuse: • IACUC Office 559-5187 • IACUC@ucmail.uc.edu • Toll-Free Anonymous Compliance Hotline 1-800-889-1547 • LAMS Veterinary Staff 558-5171

26. IACUC Contacts: Rob Anderson, Director IACUC George Babcock, Chair IACUC Kareemah Mills, Protocol Program Manager David Custer, Training Program Manager Phone: 558-5187 LAMS Contacts: Douglas Stone, DVM Director LAMS Mark Kurtzman DVM, Assoc. Director – Veterinary Care Dale Goss, Assoc. Director – Husbandry Vicki Shaw, Business Administrator Phone: 558-5171 Contact Information

27. Biological Safety The University of Cincinnati Biosafety Department has two functional components: • TheBiosafety Office • The Institutional Biosafety Committee (IBC). They work closely to ensure the safety and health of research staff and compliance with applicable laws.

28. Biosafety Office The Biosafety Office is charged with ensuring compliance with institutional requirements and federal, state and local regulations pertaining to the possession, use, transfer and disposal of biohazardous agents.  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 biohazardous materials. Biosafety Office: 3255 Eden Ave HPB G34 MLC0767 558-5210

29. Institutional Biosafety Committee The 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 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) and the current edition of the Centers for Disease Control and Prevention’s “Biohazards in Microbiological and Biomedical Laboratories” (the “BMBL” or CDC Guidelines). Gary Dean, PhD IBC Chairman 513-556-3670

30. IBC Oversight The IBC reviews all research protocols involving: • Recombinant DNA (rDNA) • Agents infectious to humans, animals or plants • Other genetically altered organisms & agents • Select agents & toxins To use any of these agents, you must complete a biosafety protocol and have it reviewed and approved by the IBC. In order to begin the process, contact Erin Dunn in the Biosafety Office for password approval

31. Federal Regulations on Use of Biohazards • The NIHand the University of Cincinnati require research involving biohazards to be reviewed and approval by the Institutional Biosafety Committee (IBC). • Section IV-B-2-b-(1-6) The institution shall establish an Institutional Biosafety Committee, whose responsibilities need not be restricted to recombinant DNAand is responsible for reviewing recombinant DNA research ..in compliance with the NIH Guidelines. • The unapproved use of biohazardous agents is in violations of NIH Guidelines and places not only individual funding, but all research funding at UC in jeopardy. • Section I-D-1. All NIH-funded projects involving recombinant DNA techniques must comply with the NIH Guidelines. Non-compliance may result in: (i) suspension, limitation, or termination of financial assistance for the noncompliant NIH-funded research project and the NIH funds for other recombinant DNA research at the institution, or (ii) a requirement for prior NIH approval of any or all recombinant DNA projects at the institution”

32. Use of Select Agents & Toxins 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 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.

33. Biosafety Office Staff E-mail:inbiocom@ucmail.uc.edu Gary E. Dean, PhD Biological Safety Officer 513-558-0065 Erin L. Dunn Biological Safety Specialist & IBC Administrator 513-558-5210 Rob Anderson Managing Director 513- 558-5187

34. Radiation Safety 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 producing devices 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 Mailing address: University of CincinnatiRadiation Safety Office 170 Panceza Way PO Box 670591Cincinnati, OH 45267-0591 Phone: 558-4110 Fax: 558-9905

35. Responsibilities: 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. 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 conditions. • The RSO, with the assistance of Radiation Safety Office (RSOf) staff, is responsible for managing the day-to-day operations of the RCSP.

36. Radiation Safety Training RAM Radiation Worker Training Schedule(for individuals who may handle radioactive materials in a research or clinical setting) BasicAdvanced RetrainingBy Month for 2007/2008 Contact Radiation Safety at 558-4110 to schedule a training session.

37. Radiation Safety Website • FAQ • Manuals, QMP & Policies • Forms • Newsletters • Isotope Fact Sheets • Isotope vendors • Training schedule • Chart of nuclides and decay calculator • Request special survey or waste pickup

38. ADMINISTRATIVE STAFF Business ManagerCarolyn HurtProgram CoordinatorDebbie Kirkpatrick Administrative Secretary IRobin DavisRecords Management OfficerTammy McCall RSOf Staff Radiation Safety Officer Victoria Morris, MS, CHP TECHNICAL STAFF Assistant Radiation Safety OfficerMike Burba, BSRadiation Safety SpecialistsKevin Imes, MSKen Egan, BSEd Case, BSJohn Zometsky, MSMichelle (Mickey) Croyle, MSSenior Health Physics TechniciansDave Root, BA Mark Powers, BSStaff Health Physics TechniciansDick Henderer Dave KobzaJanine Sumrall Bill HutzelAdam Hutzel

39. ORCRA will Assist with FDA Regulated Studies

40. Why ORCRA Review? • Between September of 2006 and January of 2007, the University of Cincinnati received 3 warning letters from the FDA regarding “objectionable conditions” and non-compliance with Federal Regulations 21 CFR §812. • A root cause of these difficulties was and is a lack of attention to and education of our investigators who hold INDs and IDEs • 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 sponsor-investigators

41. Review Policy IRB PolicyIII.08 REVIEW OF SPONSOR-INVESTIGATOR INVESTIGATIONAL NEW DRUG (IND)/INVESTIGATIONAL DEVICE EXEMPTION (IDE) RESEARCH IN HUMAN SUBJECTS RESEARCH It is the policy of the University of Cincinnati that Sponsor–Investigatorstudies be reviewed and approved in accordance with Federal Regulations. In order for an investigational drug, agent, biologic or device to be used in clinical research, an Investigational New Drug (IND) or Investigational Device Exemption (IDE) must be on file with the FDA and an IND/IDE number granted when required by Federal Regulations. • APPLICABILITY • All University of Cincinnati faculty members who sponsor (takes responsibility for and initiates a clinical investigation) an IND/IDE must be qualified to do so and have a knowledge of all applicable federal, state, and local regulations prior to submitting the IND/IDE to the FDA. As mandated by 21 CFR §312.50 (IND) and by 21 CFR § 812 (IDE), sponsors are responsible for selecting qualified investigators (when applicable) • Ongoing educational support and oversight will be performed at the discretion and direction of Office of Research Compliance and Regulatory Affairs (ORCRA) and the Institutional Review Board (IRB).

42. Review Process The following items must be submitted for review and evaluation by the Research Compliance Officer (RCO) or FDA Regulatory Specialist out of ORCRA: • Study Protocol (FDA application) to include a description of statistical analysis, benefit analysis, risk analysis and all study procedures. • The initial submission packet to the FDA including Forms 1571 and 1572. • FDA letter of IND Exemption, no rejection, or Clinical Hold release. • The investigative site's SOPs for documenting and reporting anticipated and unanticipated adverse events and/or IND Safety reports to the IRB and sponsor; and the Sponsor's SOPs for reporting to the FDA as required. • Clinical monitoring procedures, including name, address and qualifications of monitors. This function may be outsourced to a qualified individual or CRO. Documents should be submitted to: ORCRA, ML 0567, WH-13. Electronic documents should be sent to: researchcompliance@uc.edu

43. Outcome If, in the opinion of the RCO or FDA Regulatory Specialist a faculty member requires additional training to fulfill their obligations of sponsor and/or investigator, supplemental educational materials or specialized consultation services will be provided to help the sponsor-investigators fulfill their obligations. The RCO or FDA Regulatory Specialist must be satisfied as to the qualifications of the faculty member to serve as sponsor-investigator. Once ORCRA has reviewed the documents a letter is sent to the IRB office staff requesting that the protocol submission be processed according to IRB procedures. A copy of this letter is kept in the IRB protocol file as well as the ORCRA file. If the investigator has no arrangements for study monitoring, the RCO may release the protocol for processing and IRB review. The IRB will be advised that adequate resources for the study are currently unavailable and request that release of final IRB approval be held by the IRB office until such time as the PI has provided sufficient documentation that monitoring has been secured.

44. Required by the IRB Office: The IRB Office staff will confirm that all required documents have been submitted by the Investigator as required for new protocol submission and ensure they are valid: • Sponsor Statement FDA form 1571 if investigator initiated • Investigator Statement FDA form1572; and/or • Any supplemental information regarding the investigational drug, agent, or biologic supplied by the Sponsor (i.e., Investigator Brochure). • Documentation from the Sponsor or FDA that the IND or IDE number is valid (i.e., sponsor protocol or letter verifying the number).  • For Sponsor-Investigator studies, a letter from the FDA is required.  (The Investigator’s brochure is NOT an acceptable mechanism for verification.)

45. ORCRA’s Website has Links to Useful Documents • IRB Policies & Procedures • A set of SOPs for GCP and Data Monitoring • Information on FDA Reporting • Some FAQs regarding DSMB • Links to FDA websites and other assistance programs

46. Additional Materials

47. Welcome to the Research Compliance Training Site Welcome to the Research Compliance Training Site Welcome to the Research Compliance Training Site Educational Programs Hot Topics Schedule Investigator 101 IRB Seminar Orientation Program Research Education AdvisoryCommittee Membership List News and Announcements      New Policy : Demonstrating Knowledge of Human Research Protection by Researchers, December 2005 Training Instructions FAQs      Frequently asked questions Compliance Training  CITI Human Research Protection Online(Meets UC's HRP training requirement) Training HRP Instructions Continuous Professional Developmentonline compliance training Blood Borne Pathogens Biosafety HIPAA Human Research Radiation Safety Transcript UC Physicians GCP Training Self-Paced Training Competency Testing  Continuous Professional Development online compliance training Biomedical Research HRP Knowledge Exam IRB - M HRP Knowledge Exam IRB - S HRP Knowledge Exam Social and Behavioral HRP Knowledge Exam Transcript Links to Compliance Training This site is your gateway to online compliance training, online competency testing, non-online educational programs and compliance training-related news.

48. 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 ColumbusInformation 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 Frequently Asked QuestionsDrug Enforcement Agency Ohio State Board of Pharmacy SlideshowOhio State Board of Pharmacy Rules Regarding LaboratoriesUsage and Inventory Log

49. To Report Concerns: Toll-free Anonymous Compliance Hotline 1-800-889-1547 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.