IBC Standard Operating Procedures VA Long Beach Healthcare System/Research and Development

IBC Standard Operating Procedures VA Long Beach Healthcare System/Research and Development

VA Long Beach Healthcare System

Research and Development

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Institutional Biosafety Committee (IBC)

Standard Operating Procedures

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Rescission: 10/02/14

Review: Annually by the IBC and R&D Committees

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James Lohaus, Ph.D. Date

Institutional Biosafety Committee Chair

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Steven Schreiber, MD Date

Research and Development Committee Vice-Chair

Version:9/08/15 1 of 37

IBC Standard Operating Procedures VA Long Beach Healthcare System/Research and Development

Table OF CONTENTS

Purpose ...... 4

Scope...... 4

Policy...... 4

Abbreviations...... 5

Definitions...... 6

Responsibilities of the Subcommittee on Research Safety (SRS)...... 9

Infrastructure of the Institutional Biosafety Committee...... 9

Number and Qualification of Members...... 9

Core Membership...... 9

Ex-Officio Members (voting and non-voting)...... 10

Appointment of Members...... 10

Quorum and Voting...... 11

Meetings...... 11

Review Procedures...... 11

Review of the Research Protocols...... 11

Categories of Research...... 12

Full IBC Review...... 14

Review Materials...... 14

Risk Assessment...... 14

Containment...... 14

Containment Guidelines...... 15

Resources...... 18

Training...... 18

Compliance...... 18

ICF Document...... 18

Amendments & Modifications...... 18

Review of Policies and Procedures...... 18

Annual Reviews...... 18

Inventory Controls...... 19

Remediation and Follow-up...... 19

Non-Recurrent Processes...... 19

Autoclave Verification...... 19

Waste Management...... 19

Animal Disposal...... 19

Actions...... 20

Training...... 21

IBC Members...... 21

Principal Investigators...... 21

Research Staff...... 21

BSL-3 Training...... 21

Quality Improvement and Assurance...... 22

Record Keeping...... 23

Roster...... 23

Biographical Sketches...... 23

Training Reports...... 23

Incident Reports...... 23

External Inspections...... 23

Internal Inspections...... 23

Emergency Response Plans and SOPs)...... 23

Agendas and Minutes...... 24

Content...... 24

Distribution and Public Disclosure...... 24

Regulatory Non-Compliance...... 25

Audits...... 25

Actions...... 24

Reporting...... 24

Annual Report...... 24

Significant Problems...... 24

Routine Actions...... 25

References...... 27

Appendices...... 28

Application for Approval, Appendix A...... 28

Risk Assessment, Appendix B...... 29

INTRODUCTION

Purpose

This Standard Operating Procedure (SOP) describes the operating procedures of the Institutional Biosafety Committee (IBC).

Scope

1. At VALBHS, the Institutional Biosafety Committee is a subcommittee of the Research and Development Committee.
2. The IBC has overlapping functions with the Subcommittee for Research Safety (SRS) and, at VALBHS; the members of the IBC are also the members of the SRS.
3. The IBC is charged by the R&D Committee with the responsibility to maintain a Research Biosafety program that is consistent with VA policies, and NIH Biosafety Guidelines of the National Institutes of Health (NIH).
4. The “NIH Guidelines for Research Involving Recombinant DNA Molecules” are referred to in this SOP as the “NIH Guidelines”.

1. The provisions of this SOP apply to all research that is conducted completely or partially in VA facilities, conducted in approved off-site locations and facilities, or conducted by VA researchers while on VA official duty time. The research may be VA funded, funded from extra-VA sources, or conducted without direct funding. As a minimum, facility safety personnel must verify that other or remote facilities adhere to health and safety standards that are equivalent to VA standards.

Policy:

• All recombinant DNA research to be conducted by, or is under the authority of, the VALBHS must be in compliance with NIH guidelines.
• Research at VALBHS will adhere to the intent of NIH guidelines that govern recombinant DNA research as well to their specifics.

• All recombinant DNA research must be reviewed and approved by the IBC before any experimental procedures may take place.

• In addition to the IBC, research proposals must be approved by all applicable committees before any experimental procedures may be initiated.

• The VALBHS does not currently conduct experiments that involve recombinant DNA research in plants.

ABBREVIATIONS

ACOSAssociate Chief of Staff

AOAdministrative Officer

CFRCode of Federal Regulations

CHPChemical Hygiene Plan

COSChief of Staff

IBCInstitutional Biosafety Committee

IRBInstitutional Review Board

NIHNational Institutes of Health

OBAOffice of Biotechnology Activities (NIH)

ORDOffice of Research and Development, VA Central Office

OROOffice of Research Oversight

OSHAOccupational Safety and Health Administration

PIPrincipal Investigator

RACRecombinant DNA Advisory Committee

R&DResearch & Development

RCOResearch Compliance Officer

RPSSResearch Protocol Safety Survey (VA Form 10-0398)

SASSubcommittee for Animal Studies

SCIRESouthern California Institute for Research and Education

SOPStandard Operating Procedures

SOPPStandard Operating Policies and Procedures

UCIUniversity of California, Irvine

VAVeterans Administration

VAMCVA Medical Center

VMOVeterinary Medical Officer

WOCWithout Compensation

DEFINITIONS

Approval Date: The IBC SOP Approval Date is the date that the IBCapproval memo for a project is signed as approved by the IBC Chair or his/her designee.

Audit: A systematic and independent examination of trial-related activities and documents to determine whether the evaluated trial-related activities were conducted, and the data were recorded, analyzed, and accurately reported according to the (GCP), operating procedures (SOPs), good clinical practice and the applicable regulatory requirement(s) (ICH 1.6).protocol, sponsor’s standard operating procedures.

Biological Safety Officer (BSO). An individual appointed by an institution to oversee management of biosafety risks. The NIH Guidelines require that a BSO be appointed when the institution is engaged in large-scale research or production activities, or in research requiring containment at BL-3 or BL-4. The duties of the BSO are described in section IV-B-3 of the NIH Guidelines.

Biosafety Level (BL): A description of the degree of physical containment being employed to confine organisms containing recombinant DNA molecules and to reduce the potential for exposure of laboratory workers, persons outside of the laboratory, and the environment. In Appendix G of the NIH Guidelines these are graded from BL-1 (the least stringent) to BL-4 (the most stringent).

Conflict of Interest: A convergence of an investigator's private interests with his or her research interests, such that an independent observer might reasonably question whether the investigator's professional actions or decisions are improperly influenced by considerations of personal financial gain.

Documentation: All records, in any form (including, but not limited to, written, electronic, magnetic, and optical records; and scans, x-rays, and electrocardiograms) that describe or record the methods, conduct, and/or results of a trial, the factors affecting a trial, and the actions taken. (ICH 1.22)

Investigator: An individual who is under the direction of the principal investigator (PI) who is involved in some or all aspects of the research project, including the design of the study, conduct of the study, analysis and interpretation of the collected data, and writing of resulting manuscripts. An investigator may be either compensated by VA, be appointed to work without compensation (WOC), or may be an employee assigned to VA through the Intergovernmental Personnel Act of 1970. The FDA considers an investigator and a principal investigator to be synonymous.

Principal Investigator: An individual who conducts a research investigation, i.e., under whose immediate direction research is conducted, or in the event of an investigation conducted by a team of individuals, is the responsible leader of that team. The FDA considers an investigator and a principal investigator to be synonymous.

Protocol: A document that describes the objective(s), design, methodology, statistical considerations, and organization of a trial. The protocol usually also gives the background and rationale for the trial, but these could be provided in other protocol referenced documents (ICH 1.44)

Quorum: More than half of the voting members are present including at least one non-scientist. In order for research to be approved, it must receive the approval of a majority of those members present at the meeting

Recusal: When an IBC or R&D Committee or other committee member declines to participate in a matter because of a potential conflict of interest under the Code of Ethics. As distinguished from abstention, the official recusing him/herself will not be present in or participate in deliberations or voting on the matter where there are potential conflicts of interest.

Regulatory Noncompliance: Failure to adhere to institutional policies and procedures, state laws, federal laws or other regulations governing the conduct of human subjects research including failure to follow the requirements of VHA Handbook 1200.08. This includes such acts as failure to obtain or maintain approval for research or to adhere to an approved protocol, failure to submit applications for study continuing review, or adhere to the Safety Plan.

Research: as defined by the Department of Health and Human Services regulations means a systematic investigation, including research development, testing and evaluation, designed to develop or contribute to generalizable knowledge. [45 CFR 46.102(d)]

Researcher: Principal investigator or the investigator

IBC approval: The determination of the IBC that the research has been reviewed and may be conducted at an institution within the constraints set forth by the R&D Committee and by other institutional and Federal requirements.

Institution: In the context of the NIH Guidelines an institution is any public or private entity, including federal, state, and local governments.

Institutional Biosafety Committee (IBC): An institutional committee created under the NIH Guidelines to review research involving recombinant DNA. The role of IBC’s has evolved over time, and many committees also review other forms of research that entail biohazardous risks as part of their institutionally assigned responsibilities.

Institutional Review Board (IRB): An institutional committee created under Federal law that has the authority and responsibility for the review of research that involves the involvement of human subjects.

National Institutes of Health (NIH): One of the world's foremost medical research institutions and the preeminent federal funder of medical research in the U.S. The NIH, comprised of 27 separate Institutes and Centers, is one of eight health agencies within the Public Health Service, which is an agency within the U.S. Department of Health and Human Services. The goal of NIH research is to acquire knowledge to help prevent, detect, diagnose, and treat disease and disability. The NIH mission is to uncover knowledge that will lead to better health for everyone.

NIH Guidelines for Research Involving Recombinant DNA Molecules (NIH Guidelines): A document created in 1976 that outlines principles for the safe conduct of research employing recombinant DNA technology. The NIH Guidelines detail practices and procedures for the containment of various forms of recombinant DNA research, for the proper conduct of research involving genetically modified plants and animals, and for the safe conduct of human gene transfer research.

Office of Biotechnology Activities (OBA).The NIH office responsible for developing, implementing, and monitoring NIH policies and procedures for the safe conduct of recombinant DNA activities, including human gene transfer.

Recombinant DNA Advisory Committee (RAC). An NIH advisory committee whose principal role is to provide advice and recommendations to the NIH Director on (1) the conduct and oversight of research involving recombinant DNA, including the content and implementation of the NIH Guidelines, and (2) other NIH activities pertinent to recombinant DNA technology. A major element of this role is to examine the science, safety, and ethics of clinical trials that involve the transfer of recombinant DNA to humans.

Recombinant DNA molecules: Under the currentNIH Guidelines these are molecules constructed outside of living cells by joining natural or synthetic DNA segments to DNA molecules that can replicate in a living cell, or molecules that result from their replication.

Standard Operating Policy and Procedures (SOPs): Detailed, written instructions to achieve uniformity of the performance of a specific function (ICH 1.55).

Subcommittee for Animal Studies (SAS): An institutional committee created under Federal law and VA guidelines that has the authority and responsibility over research that involves the use of animals.

Suspension: An action recommended by the IBC to the R&D Committee that temporarily or permanently stops all or some of the research activities must stop until issues have been satisfactorily resolved.

SECTION 01

RESPONSIBILITIES OF THE BIOSAFETY SUBCOMMITTEE

The IBC is responsible for:

Conducting an assessment of the containment levels required by the NIH Guidelines when reviewing proposed research.

Assessing the facilities, procedures, practices, and training and expertise of personnel involved in recombinant DNA research.

Periodically reviewing recombinant DNA research to ensure compliance with NIH Guidelines.

SECTION 02

INFRASTRUCTURE OF THE INSTITUTIONAL BIOSAFETY SUBCOMMITTEE (IBC)

1. NUMBER AND QUALIFICATION OF MEMBERS

The Institutional Biosafety Committee must be comprised of no fewer than five members so selected that they collectively have experience and expertise in recombinant DNA technology and the capability to assess the safety of recombinant DNA research and to identify any potential risk to public health or the environment.

At VALBHS, the members of the SRS also serve as members of the IBC. Therefore, the members of the IBC must also fulfill the requirements of the SRS. These requirements include ex officio membership of a liaison to the R&D Committee. The SRS membership requirements are described separately in the SRS SOP. The RCO serves as a consultant to the SRS/IBC and is a permanent invited guest.

2. CORE MEMERSHIP (voting). Voting members of the IBC will include:

1. Two Unaffiliated Members. At least two members shall not be affiliated with the institution (apart from their membership on the Institutional Biosafety Committee) and who represent the interest of the surrounding community with respect to health and protection of the environment (e.g., officials of state or local public health or environmental protection agencies, members of other local governmental bodies, or persons active in medical, occupational health, or environmental concerns in the community).

1. One Animal Research Scientist. The Institutional Biosafety Committee shall include at least one scientist with expertise in animal containment principles.

3. EX-OFFICIO MEMBERS (voting). Ex-officio voting members must include:

1. The Biological Safety Officer (BSO). BSO membership is mandatory if the institution conducts recombinant DNA research at BL3, BL4, or Large Scale (greater than 10 liters).

4. EX-OFFICIO MEMBERS (non-voting). Ex-officio non-voting members will include:

1. The Administrative Officer (AO) for R&D or other non-voting representative from the R&D office.

5. APPOINTMENT OF MEMBERS

1. The IBC nominates candidates to serve as members on the committee and forwards the nominations to the R&D committee.

1. The R&D committee selects candidates and forwards their selections to the medical center Director. The R&D committee is responsible to the Director for assuring that the IBC membership fulfills the requirements outlined in section 1 above. The IBC committee coordinator maintains a roster of committee members that specifies the qualifications that each member fulfills.

1. The medical center Director must officially appoint members in writing.

1. Alternate members may be appointed. Alternate members are members who may substitute for regular members if the regular members are unable to attend a meeting. If alternate members are appointed then the roster must specify the person(s) for whom they may substitute. Alternate members should have similar expertise to the regular member that they serve as an alternate for.

1. The facility Director appoints the IBC chairperson for the term of 1 year. The IBC Chairperson may be re-appointed without any lapse in time. The IBC chairperson may not simultaneously chair the R&D Committee or another research subcommittee with one exception. That exception is that the IBC Chair person may also serve as the chair of the SRS due to the overlapping responsibilities of these two subcommittees.

1. Appointment Letters must specify:

• The term of the appointment
• The type of appointment, i.e. Chair, Core or Ex Officio
• Whether the appointment is for a Regular or Alternate member.
• The Voting Status

6. Contact Person. The AO/R&D will serve as the contact person for the IBC.

SECTION 03

QUORUM AND VOTING

All research projects involving recombinant DNA research must be approved by IBC and then by the R&D Committee prior to commencement. The IBC must review proposed research at convened meetings at which a quorum (majority of voting members) is present.

For the research to be approved, it must receive the approval of a majority of those voting members present at the meeting. A quorum must be maintained for each vote to occur. If a quorum is not maintained, the protocol must be tabled and only non-protocol related issues may be discussed.

SECTION 04

MEETINGS

1. Frequency. The IBC will meet as needed or at least yearly, at a date and frequency determined by the Chair and the Safety Committee Coordinator.

2. Agenda. An agenda is to be developed before each IBC meeting and distributed to IBC members at least one weekbefore the meeting.

3. Recusals. IBC members are informed of potential conflicts through a review of meeting agendas. Agendas are distributed no later than one week prior to each IBC meeting and contain information about the investigators, sponsors and primary reviewers of each project that will be under review. IBC members review the agenda and will declare any potential conflicts of interest prior to the beginning of project reviews.

In general, the IBC member will recuse him or herself from participation in the discussion and vote. If there is any question as to whether or not a conflict exists then the full IBC will discuss the conflict of interest without the member present to determine if a conflict of interest is present. If a conflict of interest is present then recusal will be required.

SECTION 05

REVIEW PROCEDURES

1. Review of Research Protocols. The IBC is responsible for reviewing annually all active research protocols involving biological, chemical, physical, and radiation hazards, regardless of funding status or source.

Principal investigators (PI’s) are responsible for identifying any procedures that may involve the use of recombinant DNA research. PI’s will make this disclosure on VHA form 10-0398.The Subcommittee for Research Safety (SRS) will review PI disclosures and will refer the matter to the IBC if it is determined that the procedures may involve the use of recombinant DNA research.

1. Categories of Research. The IBC, or the IBC Chair acting on behalf of the IBC, will first determine the category of the proposed research.

1. Excluded Research. Investigators who wish to perform this type of research should contact the ACOS R&D. The LBVA does not currently permit research that involves recombinant DNA in the following categories:

• Whole plants
• Experiments involving more than 10 liters of culture.

1. Exempt Research. The following recombinant DNA molecules are exempt from the NIH Guidelines and registration with, and review by the

IBC is not required: