Research Involving Recombinant DNA Molecules (rDNA)
1. Regulatory Requirements:
The NIH Guidelines outline procedures involving use of recombinant DNA and describe the roles, responsibilities, and relationships among the principal investigator (PI), the Institutional Biosafety Committee (rDNA review committee), and the National Institutes of Health (NIH).
The NIH Guidelines also contain helpful information regarding physical and biological containment guidelines and risk assessment (categorized into Risk Group 1, 2, 3, or 4).
Compliance with the NIH Guidelines is a necessity due to federal NIH funding received by UT Arlington. All projects involving recombinant DNA techniques conducted at or sponsored by an institution that receives NIH funds for projects involving such techniques must comply with the NIH Guidelines. Noncompliance may result in: (i) suspension, limitation, or termination of NIH funds for allrecombinant DNA research at the institution, or (ii) a requirement for prior NIH approval of any or all recombinant DNA projects at the institution.
UT ARLINGTON'S POLICY & PROCEDURES FOR RESEARCH INVOLVING RECOMBINANT DNA
UT Arlington’s Policy & Procedures for Research Involving Recombinant DNA Molecules define and describe in great detail: covered recombinant DNA experiments, applicability, responsibilities of the UT Arlington IBC and PIs, training requirements, containment guidelines, and the IBC’s research review process and procedures.
BIOSAFETY IN MICROBIOLOGICAL AND BIOMEDICAL LABORATORIES, 5TH EDITION
The Centers for Disease Control (CDC’s) Biosafety in Microbiological and Biomedical Laboratories, 5th edition (the “BMBL”) establishes a code of practice for biosafety in laboratories - one that all members of the research and laboratory community can utilize to safeguard themselves and their colleagues, and to protect the public health and environment.
The BMBL contains helpful information regarding risk assessment, laboratory safety standards, containment guidelines, and categorization of biological agents/material into containment levels (referred to as Biosafety Level 1, 2, 3, or 4). These classifications are based on infectivity, severity of disease, transmissibility, and the nature of the work being conducted.
Recombinant DNA molecules are defined as either: (i) molecules that are constructed outside living cells by joining natural or synthetic DNA segments to DNA molecules that can replicate in a living cell, or (ii) molecules that result from the replication of those described in (i) above.
Synthetic DNA segments which are likely to yield a potentially harmful polynucleotide or polypeptide (e.g., a toxin or a pharmacologically active agent) are considered as equivalent to their natural DNA counterpart.
Genomic DNA of plants and bacteria that have acquired a transposable element, even if the latter was donated from a recombinant vector no longer present, are not subject to the NIH Guidelines unless the transposon itself contains recombinant DNA.
The Institutional Biosafety Committee (IBC), in accordance with the NIH Guidelines, is a University-wide standing committee responsible for oversight and review of rDNA research including independent assessment of: containment levels, laboratory facilities, procedures, practices, health surveillance, and training and expertise of personnel involved in the rDNA research.
Additionally, the IBC provides consultation to the Institution’s research community including faculty, staff, and students, concerning issues of biohazards, laboratory biosafety procedures, and appropriate biological techniques (best practices) to minimize risk and hazard.
projects involving recombinant DNA, regardless of funding, must be reviewed by
the UT Arlington Institutional Biosafety Committee (IBC) prior to initiation.
4. Application Process and Review Timeline:
PROTOCOL SUBMISSION AND REVIEW PROCEDURES FOR rDNA RESEARCH
For all experiments involving recombinant DNA, including those which are considered exempt by NIH Guidelines, Principal Investigators must submit an IBC Protocol Application for (i) exemption determination and documentation or (ii) IBC review and approval of non-exempt experiments. Protocol Application should be submitted to the Office of Research Administration:
E-mail to email@example.com
• Drop off at 202 E. Border St., Suite 214
• Mail to Box 19188
• Fax to 817-272-5808
The IBC Protocol Application Form is divided into 2 parts. Experiments qualifying for exemption under the NIH Guidelines Section III-F require completion of Part I of the Protocol Application. Experiments that do not qualify for exemption under the NIH Guidelines Section III-F (non-exempt) require completion of both Part I and Part II of the Protocol Application
EXEMPT rDNA EXPERIMENTS
The Protocol Application will be initially reviewed by the IBC Chairperson to determine if it falls under the 6 categories of exemption as described in the NIH Guidelines Section III-F:
rDNA molecules that are not in organisms or viruses.
(ii). rDNA molecules that consist entirely of DNA segments from a single nonchromosomal or viral DNA source, though one or more of the segments may be a synthetic equivalent.
(iii). rDNA molecules that consist entirely of DNA from a prokaryotic host including its indigenous plasmids or viruses when propagated only in that host (or a closely related strain of the same species), or when transferred to another host by well established physiological means.
(iv). rDNA molecules that consist entirely of DNA from a eukaryotic host including its chloroplasts, mitochondria, or plasmids (but excluding viruses) when propagated only in that host (or a closely related strain of the same species).
(v). rDNA molecules that consist entirely of DNA segments from different species that exchange DNA by known physiological processes, though one or more of the segments may be a synthetic equivalent. See Appendix A, Exemptions Under Section III-F-5--Sublists of Natural Exchangers, for a list of natural exchangers that are exempt from the NIH Guidelines.
(vi). rDNA molecules that do not present a significant risk to health or the environment (see Section IV-C-1-b-(1)-(c), Major Actions), as determined by NIH. **See Appendix C, Exemptions under Section III-F-6 for other classes of experiments which are exempt from the NIH Guidelines.**
Experiments determined as exempt by the IBC Chairperson will receive an acknowledgement letter from the IBC documenting the exemption and determination. No further action is required by the Principal Investigator unless there is a change in procedures or the use of rDNA that would affect the IBC’s initial determination as exempt (allowable exemptions are outlined in NIH Guidelines Section III-F).
NON-EXEMPT rDNA EXPERIMENTS
Experiments that do not meet criteria for exemption as outlined in NIH Guidelines Section III-F will be scheduled for review at the next fully convened IBC meeting. It is strongly recommended that the Principal Investigator attend the meeting to answer any questions or address concerns of the IBC, during the review process.
IBC will consider the Protocol Application in conjunction the NIH
Guidelines’ review requirements including:
(i). The source(s) of DNA.
(ii). The nature of the inserted DNA sequences.
(iii). The host(s) and vector(s) to be used.
(iv). If an attempt will be made to obtain expression of a foreign gene, and if so, the protein that will be produced.
(v). The containment conditions that will be implemented as specified in the NIH Guidelines.
If the IBC requests additional information or modifications to secure approval following review of aProtocol Application , the Office of Research Administration or the IBC Chairperson will summarize these requests and notify the Principal Investigator. Final approval of research protocols will be communicated to Principal Investigators via an approval letter issued by the IBC Chairperson.
LABORATORY CERTIFICATION AND SAFETY
Laboratories conducting recombinant DNA or biological research are classified as Biosafety Level 1, 2, 3, or 4 based on the guidelines in CDC’s Biosafety in Microbiological and Biomedical Laboratories, 5th edition.
Recombinant DNA experiments requiring Biosafety Level 2 containment will require certification of the laboratory to ensure appropriate safety practices, equipment, and facility design. Therefore, the Principal Investigator should notify Environmental Health & Safety (EH&S, 817-272-2185 firstname.lastname@example.org) as soon as possible once determined these levels of containment will be necessary. The laboratory certification process may occur simultaneously with the IBC protocol review process, but final approval of the Protocol Application will not be granted until the EH&S laboratory certification is complete.
Currently, there are no research projects on the UTA campus classified above Biosafety Levels 1 or 2. Use of pathogenic agents classified as Biosafety Levels 3 or 4 will require involvement and approval by UTA Administration. If you are considering using any of the agents classified as BSL 3 or BSL 4, please notify Environmental Health & Safety and/or the Office of Research Administration.
COLLABORATIVE rDNA RESEARCH
When research covered by the NIH Guidelines is conducted at or in cooperation with another entity, all provisions remain in effect for that research. The UT Arlington IBC may accept, for the purpose of meeting IBC review requirements, the review of an IBC established under another policy of compliance with the NIH. Such acceptance must be in writing, approved and signed by UT Arlington’s IBC Chairperson, and approved and signed by correlative officials of each of the other cooperating institutions.
In accordance with the NIH
Guidelines Appendix G, the Principal Investigator is responsible
for training all personnel involved in the proposed rDNA project in matters of
potential biohazards, relevant biosafety practices, aseptic technique,
laboratory emergency procedures, and the biology of the organisms used in the
experiment(s). This site-specific training must be documented by the PI (dates,
attendees, topics) and made available to the IBC or Environmental Health &
Safety as requested.
In addition to site-specific training performed by the PI, the PI and all protocol personnel must complete the online module entitled, “Working with Recombinant DNA Molecules.” It can be accessed using a UTA net ID and password at the following site: https://www.uta.edu/ra/real/researchspace.php?view=7.
6. Student Responsibilities Following Research Approval:
PERIODIC REVIEW OF APPROVED rDNA EXPERIMENTS
In accordance with the NIH Guidelines, Section IV-B-2, the IBC will periodically review approved recombinant DNA research to ensure compliance with the NIH Guidelines. Periodic reviews will be scheduled at the discretion of the IBC and communicated to the Principal Investigators. Typically, periodic reviews take place on an annual basis. Principal Investigators are responsible for submitting information requested via the Annual Report Form in a timely manner, meeting the deadlines established by the IBC.
REVIEW OF MODIFICATIONS TO APPROVED rDNA EXPERIMENTS
Principal Investigator is responsible for notifying the IBC of any major
changes in approved rDNA experiments before initiation. For example, the PI
shall submit an Amendment Form (hyperlink to form) for IBC review before
implementation of any of the following:
(i). A change in host or vector.
(ii). A change in the donor species or nature of the DNA segment selected.
(iii). A change of project title.
(iv). A change in funding agency.
(v). A change in the location of work/experiments.
(vi). A change of the Principal Investigator or laboratory personnel.
RESPONSIBILITY TO REPORT INCIDENTS/ACCIDENTS/ILLNESSES
After seeking medical attention (if necessary), accidents and injuries that take place in the lab must be reported immediately (within 24 hours) to Environmental Health & Safety. The PI must also promptly report (within 5 business days) any significant problems, violations of the NIH Guidelines , or any significant research-related accidents and illnesses to the IBC and Office of Research Administration.