Case Western Reserve University
Institutional Biosafety Committee
Post Approval Monitoring Procedures
Purpose
Research involving recombinant and synthetic nucleic acid molecules conducted at or sponsored by
Case Western Reserve University (CWRU), or research conducted by CWRU faculty members or
students, must be conducted in a manner that does not pose a significant risk to the health or safety of
laboratory workers, others in the University community, or the public, or the environment. Federal
law on use of recombinant and synthetic nucleic acid molecules mandates the establishment of the
Institutional Biosafety Committee (IBC), which reviews, approves and oversees projects involving
recombinant and synthetic nucleic acid molecules.
Investigators and research staff conducting research approved by the CWRU IBC are responsible for
ensuring compliance with federal regulations, policies and procedures, as well as local institutional
policies. In order to assist researchers and facilitate compliance with CWRU IBC approval and
stipulations for the conduct of IBC-regulated research, the CWRU Research Compliance Office has
established a process for post approval monitoring (PAM) and review. This PAM process will involve
research compliance monitoring of CWRU IBC and investigator research records.
Research compliance review and monitoring is conducted to promote quality assurance and
continuous quality improvement through participation in prospective monitoring visits. The goal is to
educate the CWRU research community regarding responsible conduct of research and to evaluate the
understanding of safety and ethical standards governing IBC-regulated research through the periodic
monitoring process.
The program and process provides monitoring and review of a research study to ensure proper
conduct, records and reports are performed as stated in the IBC-approved protocol. It also involves
the review of standard operating procedures, good laboratory practices, and regulatory requirements.
Post approval monitoring for the CWRU IBC compares the implementation of the IBC research
protocol by the investigator to the specifics of the CWRU IBC-approved protocol or records. The
program has developed a Post Approval Monitoring Review Form that can be used as a self-assessment tool
in preparation for a PAM review or independently at the Investigator’s discretion.
This is a confidential process that will ensure compliance with the National Institutes of Health Guidelines
for Research Involving Recombinant or Synthetic Nucleic Acid Molecules (NIH Guidelines), November 2013. The
NIH Guidelines state that the CWRU IBC is responsible for “periodically reviewing recombinant or
synthetic nucleic acid molecule research conducted at the institution to ensure compliance with the
NIH Guidelines.” In addition, the NIH Guidelines specify that the Biological Safety Officer (BSO) is
charged with "conducting periodic inspections to ensure that laboratory standards are rigorously
followed."
Institutional Cooperation
The CWRU Research Compliance Office works closely with the CWRU Environmental Health &
Safety (EH&S) Department to monitor the review and IBC-regulated research. The CWRU IBC
administrative staff members are voting members on the CWRU Laboratory Safety Committee (LSC),
which is managed under EH&S. The LSC is charged with providing safety education, training,
monitoring, laboratory inspection and incident reporting. An annual report is created, as per LSC
operating guidelines, with input of LSC membership. Any emergent or serious events requiring
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Institutional Biosafety Committee
Post Approval Monitoring Procedures
additional review, oversight, or reporting would be handled urgently in conjunction with the IBC
administration.
The IBC administration works closely with other safety and ethics committees across the CWRU
campus, including the Institutional Animal Care and Use Committees (IACUCs), local hospital
affiliate Institutional Review Boards (IRBs), the CWRU Human Stem Cell Research Oversight
(HSCRO) Committee, the Institutional Review Entity (IRE) for dual use research of concern
(DURC), the Pathogens Committee, and Environmental Health & Safety. The IBC Assistant Director
is a voting member of the CWRU IACUC and is the administrator for the HSCRO Committee and
the IRE. The Executive Director for Research Compliance is an ex-officio member of the CWRU
IBC, HSCRO, and the MetroHealth Medical Center, University Hospitals Case Medical Center, and
Louis Stokes Cleveland Veteran’s Administration Medical Center IRBs.
Definitions
Directed (For Cause) Monitoring: Directed monitoring of CWRU IBC-approved research occurs
in response to identified concerns. Examples of identified concerns include an externally initiated
complaint (NIH, Office of Biotechnology Activities (OBA), OHRP, FDA or study sponsor) of
potential protocol violations or non-compliance; complaint or concern from a participant and/or a
participant’s family member; concern raised by an employee; IBC directive or concern; and/or
investigator with a history of poor adherence to research policies and procedures.
Investigator Records: Records to be kept by the Investigator and which are subject to review during
the monitoring visit include, as applicable: study procedures/protocol as approved by the CWRU
IBC, laboratory safety manual, exposure control plan (ECP), chemical hygiene plan (CHP), inspection
records, laboratory safety and incident reporting. For human gene therapy and vaccine trials,
additional records may be reviewed, and include the following: regulatory binder, informed consent
document(s) for each consented participant, participant’s research records, source documentation,
inclusion/exclusion criteria, pharmacy records, and occurrence and reporting of adverse events,
unanticipated problems and protocol deviations. The Investigator is to maintain copies of all
correspondence between the Investigator and the CWRU IBC.
Monitoring: Reviewing a study to ensure proper conduct, records and reports are performed as
stated in the IBC approved protocol. It also involves the review of applicable local institutional
research standard operating policies and procedures and other safety and regulatory requirements.
Also refer to definitions for directed (for cause) and prospective (routine) monitoring.
Non-Compliance: Failure to comply with any applicable federal, state and/or local laws and
regulations or the requirements or determinations of the IBC. Non-compliance actions may range
from minor to serious, be unintentional or willful, and may occur once or more than once. The degree
of non-compliance is evaluated on a case-by-case basis and will take into account such considerations
as to what degree subjects were harmed or placed at an increased risk and willfulness of the noncompliance. Where appropriate, reviews for non-compliance will conducted with the assistance of the
CWRU BSO and his/her colleagues in EH&S. Sources of allegations of non-compliance can include
findings during EHS audits and/or safety inspections.
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Post Approval Monitoring Procedures
Prospective (Routine) Monitoring: Prospective, proactive, routine monitoring is conducted to
assess investigator compliance with Federal, state and local laws, and CWRU and IBC policies.
Protocols for prospective monitoring are selected for routine monitoring will be protocol-driven and
selected by performing a random query of the CWRU IBC protocol database identifying active
studies. Protocol review and monitoring may be requested on a voluntary basis by the Investigator in
preparation for a sponsor or other monitoring or audit or by the Departmental Chairperson.
“For Cause” Terminations: When research on an approved protocol is partially or completely
stopped for some period of time, by the CWRU IBC.
Process
Investigator Records
Eligibility for Post Approval Monitoring
Any site conducting IBC-regulated related research, where the CWRU IBC acts as IBC of record may
undergo monitoring in order to assure the Federal guideline, regulations, state and local law,
institutional and IBC policies and procedures are followed, and to provide education to Investigators
and research staff. Investigators and research staff will be contacted in advance. An investigator has
the option to postpone or re-schedule a monitoring visit within a reasonable period of time, but not to
decline monitoring and quality assurance review.
The CWRU Office of Research Compliance will monitor a convenience sampling, annually, of a
minimum of 3% of all active research protocols, where active signifies that there is an approved IBC
registration on file. Of the protocols to be monitored, there will be an attempt to balance the
percentage of categories, including federally-funded protocols, protocols involving animal models, and
therapeutic protocols.
The intent is to monitor all departments on a rotating cycle. Active research studies that are not part
of defined departments will be included in the monitoring selection and may be selected outside of a
defined cycle.
Records to Be Reviewed
In all studies, regardless of category, the currently approved IBC application, all associated
amendments, and attachments will be reviewed in detail. For laboratory and animal protocols, the
IBC will review study procedures/protocol as approved by the CWRU IBC, laboratory safety manual,
exposure control plan (ECP), chemical hygiene plan (CHP), inspection records, laboratory safety and
incident reporting.
For human gene therapy and vaccine studies, additional records may be reviewed, and include the
following: regulatory binder, informed consent document(s) for each consented participant,
participant’s research records, source documentation, inclusion/exclusion criteria, pharmacy records,
and occurrence and reporting of adverse events, unanticipated problems and protocol deviations. The
Investigator is to maintain copies of all correspondence between the Investigator and the CWRU IBC.
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For clinical trials, where and when it is applicable, a sampling of patients enrolled at the start, midpoint, and end/recent patients enrolled will be selected. If the total number of subject records is 5 or
below, all subject case report forms and medical records will be reviewed.
Reporting of Findings
At the completion of the inspection the Investigator and/or approved study staff will receive a verbal
summary of the review with reinforcement of safety, ethical and regulatory responsibilities. The
Investigator and study staff will be given the opportunity, where possible, to respond to and to correct
any findings, in person, at the time of the close-out interview. Following the monitoring visit, the
approved study staff members and the Investigator will receive a written summary report of the PAM
review and any findings discovered while reviewing the protocol records.
The written summary of findings will be delivered via electronic mail and maintained in the CWRU
Office of Research Compliance. The summary report and findings may include, as appropriate,
required actions needed to correct any findings or deficiencies. Monitoring and quality assurance
reviews which identify substantive deficiencies are referred promptly to the Executive Director of
Research Compliance and IBC Chair. Significant findings will be addressed by the IBC through the
process described below.
Results of all monitoring reviews, both prospective and directed, are reported to the IBC
Committee on a semi-annual basis. The CWRU IBC is required to report significant findings or
violations to the National Institutions of Health (NIH) Office of Biotechnology Activity (OBA), as
outlined in the NIH Guidelines. Copies of all relevant correspondence are maintained in the CWRU
Office of Research Compliance.
Addressing Significant Findings
If significant findings or deficiencies are identified, in addition to other actions that may be taken by
CWRU and the IBC, the summary report will be sent to the next IBC meeting for review by the full
committee. The IBC will require implementation of an overall plan to prevent reoccurrence of events
or actions leading to deficiencies or findings. Details of the plan may include, but are not limited to,
the following:
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The IBC may require additional modifications to the protocol.
The IBC may require more frequent, established monitoring and review, such as updates by
the Investigator in addition to the required continuing review reports.
The IBC may require that the Investigator and/or study staff undergo additional training or
education.
The PAM reviewer and the CWRU IBC will work with the Investigator and study staff to make any
required changes to bring the IBC protocol back into compliance.
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IBC Records
In conjunction with the investigator record review, the Office of Research Compliance conducts a
review of the CWRU IBC records. The Office of Research Compliance also reviews the IBC
administrative process and actions related to the protocol and study review, including full committee
meeting minutes, administrative action reports, and other IBC files and records to ensure that the IBC
acted in accordance with federal regulations and IBC policy and that the IBC records are properly
maintained in accordance with federal regulations as well as IBC and institutional policy. As a result
of the monitoring and quality assurance review, the Office of Research Compliance may suggest and
identify changes to IBC policies, procedures or forms to improve their clarity or accuracy.
Any policy and procedure modifications will be reviewed and adopted according to the effective IBC
procedures for review and approval. These findings and suggested changes, if any, will be shared with
the Executive Director of Research Compliance and the IBC Chair. The CWRU IBC is required to
report significant finds or violations to the National Institutions of Health (NIH) Office of
Biotechnology Activity (OBA), as outlined in the NIH Guidelines.
Regulatory Citations
National Institutes of Health Guidelines for Research Involving Recombinant or Synthetic Nucleic Acid Molecules
(NIH Guidelines), November 2013. http://oba.od.nih.gov/oba/rac/Guidelines/NIH_Guidelines.htm
Related Procedures and Policies:
CWRU IBC Procedures for Use of Recombinant or Synthetic Nucleic Acid Molecules
CWRU IBC Procedures for Continuing Review and Notifications
CWRU IBC Administrative Office Procedures
Special Considerations rDNA Revised
Related Form:
Post Approval Monitoring Review Form
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