Help Information for rDNA Registration Document questions

A. Funding Source

Enter the name of your funding agency. Multiple funding sources may be added if necessary, by clicking the Add Source button. The IBC does not require separate rDNA Registration Documents for each grant/funding source; a PI may submit a single document which encompasses all research with recombinant and synthetic nucleic acid molecules performed in that laboratory.

  • Examples include: National Institutes of Health (NIH), National Science Foundation (NSF), US Department of Health & Human Services (DHHS), Department of Defense (DOD), Department of Veterans’ Affairs, Internal Funding, etc.

B. Replacing a previously approved protocol

rDNA Registration Documents are approved for a 3-year period and must be renewed if the research has not been completed by the expiration date.  PIs may also wish to combine multiple previously approved rDNA documents into a single document and subsequently archive the multiple documents prior to their expiration date.

Please include the rDNA Registration Document number(s) that this protocol will replace.

C. Overall goals

Briefly (1-5 sentences) describe the overall goal or purpose of this project, providing enough detail to allow the committee to understand the scope of the project.

D. rDNA Research – NIH Guidelines training course

The rDNA training course is designed to familiarize researchers with the NIH Guidelines and provide information regarding the roles and responsibilities of various personnel involved with rDNA research at the University of Iowa. This course is available through ICON. Depending on whether you are a UI paid employee or not, the link to access the training will be different; instructions are provided through EHS.

Completion of the rDNA Research-NIH Guidelines course is required for all staff involved in the project.

E. Laboratory experience

Please list relevant laboratory experience with the listed procedures and organisms.  The IBC will use this information to determine whether the individuals are appropriately trained and can carry out the described research in the document or if additional training must be provided to staff.  Should additional training be required, the IBC will ensure those individuals performing the training have the appropriate experience and knowledge to do so.

Depending on the research proposed, some examples include:

  • PI has prior experience working with the listed organisms and procedures.
  • PI received a Ph.D. in virology and has prior experience cloning and delivering recombinant viral vectors.
  • The Co-PI has prior experience cloning plasmids in E. coli.

F. Co-Investigators

Co-investigators should include faculty members or research scientists who will also be creating, manipulating or otherwise utilizing the recombinant DNA and/or recombinant organism(s).

Prior to implementation of the eIBC Registration Document Management System, research staff were added as Co-PIs in order to submit amendments on behalf of the PI.  The eIBC allows PIs to authorize research staff to act as a proxy and edit and submit registration documents and amendments on the PI’s behalf.  Research staff should no longer be added as a Co-PI solely for amendment submission purposes.

G. Technical staff and student personnel

List all staff and student personnel who will be involved with creating, manipulating or otherwise utilizing the recombinant DNA and/or recombinant organism(s). 

H. 

 

I. Working with human cells/human material

Personnel working with specimens of human origin (eg. blood, primary cells, cell lines, tissues) are required to complete an initial Bloodborne Pathogens training course, and the Bloodborne Refresher course annually thereafter. Cell lines from ATCC are not tested sufficiently to exempt them from possible BBP exposure; as a result, all employees who work with human cell lines, including those obtained from ATCC, are considered “at risk” for exposure to BBP and must receive proper training.

Initial bloodborne pathogen training for research staff in the College of Public Health includes Bloodborne Pathogens-College of Public Health (W130BO); all other research staff should complete the Bloodborne Pathogens-Lab course (W003BO).  Subsequently, all research staff should complete the Bloodborne Pathogens Refresher training (W132BO) to satisfy the annual training requirement.

J. Hands-on training, additional staff listing

List any additional staff not included under the PI, Co-PI or Technical/Student Personnel who will be responsible for training new or inexperienced staff and describe their qualifications. Some labs may choose to receive viral vector training from the Viral Vector Core, or another researcher on campus who is familiar with handling the recombinant material.

Depending on the research proposed, some examples include:

  • The PI and many of the lab staff do not yet have laboratory experience working with viral vectors. However, staff in the Viral Vector Core has worked with the relevant organisms and methods for more than 10 years, and will provide training to laboratory personnel.
  • Before initiating the study, all personnel will be trained by a sponsor representative during the site visit. 
  • Training on rDNA manipulations and transfection of cell lines will be provided by Dr. John Doe in the Department of Microbiology who has over 10 years’ experience handling recombinant materials.

K. PI Co-PI Lab Locations: 

List the PI and Co-PI(s) laboratories where this rDNA work will be conducted.

By clicking on the button you will be able to select a building from a drop down list and subsequently enter a room number associated with the selected building.  Please add all locations in which the rDNA will be utilized, including the PI and Co-PI’s laboratories by clicking on “Add Lab Location” button within the rDNA document.

L. Additional lab locations

Other than the rooms listed under the PI and Co-PI(s), will any additional laboratories or core facilities work with the recombinant DNA or synthetic nucleic acids, either in its construction, or propagation as a part of the project? Depending on the work done elsewhere, the PI of that laboratory may also be required to obtain IBC approval.

State whether any other labs/core facilities will be involved with this rDNA work (e.g., vector construction, propagation, creation of transgenics, etc.).  Check the appropriate box identifying which labs will be involved with this project and describe the work that will be done at that location/facility.

Flow Cytometry Core Facility:

Flow Cytometry Core Facility under Dr. Zuhair Ballas (Facility Director)/Justin Fishbaugh (Technical Director), 48 EMRB.

High Throughput Screening Core facility:

High throughput Screening facility under Dr. Meng Wu, 316 PHAR.

Genome Editing Core Facility:

Genome Editing Facility under Dr. William Paradee, MRF.

Microscopy Core Facility:

Central Microscopy Research Facility under Randy Nessler, 81 EMRB.

  • Example:  Central Microscopy core will be used to visualize cells containing rDNA constructs utilized in this study.

Viral Vector Core Facility:

Viral Vector Core under Dr. Patrick Sinn, 221 EMRB.

Depending on the research proposed, some examples include:

  • Viral Vector Core will be utilized to make the AAV viral vector constructs used in this study.
  • The Viral Vector core will amplify, purify and store the adenoviral vector constructs.

Other Lab Locations:

Other lab locations would include collaborators (not listed as Co-PIs) on or off campus.

Depending on the research proposed, some examples include:

  • Other Lab Locations: Dr. John Doe, University of X
    Dr. Doe will supply the vector and construct.
    Dr. Doe will provide the knock-out mice.
  • Iowa Institute of Human Genetics - Genomics Division will be used to confirm sequence of rDNA constructs.

M. Decreased biosafety level justification

The biosafety level for handling the recombinant constructs listed within the table associated with this rDNA protocol must be used when handling the constructs. Generally, work with known agents should be conducted at the biosafety level recommended in Section VIII of the Biosafety in Microbiological and Biomedical Laboratories Manual (http://www.cdc.gov/biosafety/publications/bmbl5/index.htm) or Appendix B of the NIH Guidelines (http://osp.od.nih.gov/office-biotechnology-activities/biosafety/nih-guid...).  When information is available to suggest that virulence, pathogenicity, antibiotic resistance patterns, vaccine and treatment availability, or other factors are significantly altered, more or less stringent biosafety practices may be specified.

A decreased biosafety level may be assigned if justification is provided for reduced biohazard potential. 

Depending on the research proposed, an example includes the sorting of human cells at the Flow Cytometry Facility.  Unless justification is provided, research with human cells would be assigned BSL2 containment.  However, if the cells will be fixed prior to sorting, BSL1 containment would be appropriate at the Flow Cytometry Facility.

N. Vaccines

If personnel will be working with infectious forms of viruses, bacteria, parasites etc., the transmission of which can be prevented by a vaccine, the vaccine should be made available to all affected workers at no cost to the employee.  The PI should work with University Employee Health Clinic (UEHC) to determine the need and availability of receiving the vaccination.

Vaccines have been approved by the FDA for the following agents [See (http://www.fda.gov/BiologicsBloodVaccines/Vaccines/ApprovedProducts/ucm0...) for the FDA’s current list]:

  • Bacillus anthracis (Anthrax)
  • Bordetella pertussis (Pertussis)
  • Corynebacterium diphtheriae (Diphtheria)
  • Haemophilus influenza Type b
  • Hepatitis A virus
  • Hepatitis B virus
  • Human papillomavirus (HPV)
  • Influenzae virus
  • Japanese encephalitis virus
  • Measles virus
  • Mumps virus
  • Neisseria meningitidis (Meningococcal disease)
  • Polio virus
  • Rabies virus
  • Rotavirus
  • Rubella virus
  • Mycobacterium tuberculosis (TB)
  • Salmonella typhi (Typhoid fever)
  • Smallpox virus
  • Streptococcus pneumoniae (Pneumococcus)
  • Clostridium tetani toxin (Tetanus)
  • Vaccinia virus (Cowpox)
  • Varicella zoster virus (Chicken pox)

O. Health/medical restrictions or precautions

Any health or medical restrictions/precautions recommended for staff working on this project should be described.  A statement regarding laboratory staff being offered any applicable medical surveillance or monitoring at UEHC should be included here. 

Depending on the research proposed, some examples include:

  • No immunocompromised or pregnant individuals will be allowed to work with vaccinia virus.
  • Annual medical surveillance will be completed by all individuals working in the BSL3 laboratory.
  • Individuals working with TB will undergo PPD testing twice per year.

P. Replication competency for viral vectors

Describe the replication competency for each viral vector listed in the rDNA Registration Document.  An explanation for any replication defective vectors must detail the molecular basis for this designation.

Depending on the research proposed, some examples include:

  • Adenovirus: E1, E3 deleted
  • AAV: rep/cap deleted
  • FIV/HIV: gag, pol, env deleted
  • No structural genes are present in the packaged viral genome, hence no replication competent virus may be produced.
  • Baculovirus vector is an insect-specific virus and will not replicate in mammalian cells.
  • Hep B: replication competent

Q. Synthetic nucleic acids

According to NIH Guidelines, synthetic nucleic acids are defined as nucleic acid molecules that are chemically or by other means synthesized or amplified, including those that are chemically or otherwise modified, but can base pair with naturally occurring nucleic acids.

Synthetic nucleic acids must be registered with the IBC unless they are exempt from the NIH Guidelines.  Exempt nucleic acids include those that:

i.   cannot replicate or generate nucleic acids that can replicate in any living cell
ii.  are not designated to integrate into DNA
iii. do not produce a toxin that is lethal for vertebrates at an LD 50 of less than 100 nanograms/Kg body weight.

Any use of a plasmid or viral vector to deliver synthetic nucleic acids must be registered with the IBC.  An exempt use would include double-stranded oligonucleotides such as a synthetic short-interfering RNA (siRNA).

If synthetic nucleic acids will be used, please describe how the expression within the host will be altered.  This information will assist the committee in determining the proper containment level to assign to this construct.  For example, will the RNAi inhibit expression of tumor suppresser genes, disrupt immunity, or expand tropism/host range of a pathogen?

R. Toxins

Oversight for deliberate cloning of genes coding for the biosynthesis of molecules toxic for vertebrates is dependent on the LD50 of the toxin; details of this oversight are found in Appendix F of the NIH Guidelines.

  • The cloning of genes coding for molecules toxic for vertebrates that have an LD50 of < 100 nanograms per kilogram body weight (e.g., microbial toxins such as the botulinum toxins, tetanus toxin, diphtheria toxin, Shigella dysenteriae neurotoxin) requires IBC and NIH/OBA approval before initiation.
  • Experiments involving genes coding for toxin molecules with an LD50 of < 100 micrograms per kilogram and > 100 nanograms per kilogram body weight require IBC approval and registration with NIH/OBA prior to initiating the experiments.
  • No specific restrictions shall apply to the cloning of genes if the protein specified by the gene has an LD50 ≥ 100 micrograms per kilogram of body weight.

A list of toxin molecules classified as to LD50 is available by contacting NIH/OBA.

The IBC and EHS Biosafety staff will work with the PI to obtain or register with NIH/OBA, when appropriate; the IBC will withhold protocol approval until all required registration/approval with NIH/OBA is complete. 

S. Expressed oncogenes

Special care should be taken in determining safety precautions and containment levels if the experiments necessitate the insertion of known oncogenes, or genes with high oncogenic potential.

Depending on the research proposed, additional safety precautions may include:

  • Double gloving when handling the oncogenic constructs, and paying special attention to glove punctures.
  • Eliminating the use of glass.
  • Requiring the use of safety equipped sharps.​

T. Expressed antibiotic resistance genes

Include all antibiotic resistance genes that will be expressed in bacteria or cell culture; antibiotic resistance genes that are already present in a commercially available vector and those cloned by laboratorians should be listed.

If the proposed transfer of these genes will be clinically relevant, NIH/OBA must approve this research prior to IBC review.  Clinically relevant antibiotic resistance genes are those that confer resistance to antibiotics that are used to treat human or animal infections caused by organisms into which the resistance genes will be transferred.  Please contact Haley Sinn (5-9553) or Aswathy Sreedharan (5-9547) at the Biosafety Office, or email ehs-rdna@uiowa.edu for further guidance.

U. Dual Use

According to the United States Government Policy, Dual Use Research is certain types of research conducted for legitimate purposes can be utilized for both benevolent and harmful purposes. Dual Use Research of Concern (DURC) is a subset of Dual Use Research which involves Life Sciences research that, based on current understanding, can be reasonably anticipated to provide knowledge, information, products, or technologies that could be directly misapplied to pose a significant threat with broad potential consequences to public health and safety, agricultural crops and other plants, animals, the environment, material or national security. Further information regarding the agents (15) and categories of experiments (7) evaluated under DURC potential is available at http://osp.od.nih.gov/office-biotechnology-activities/biosecurity/dual-u... and through EHS.

The United States Government’s oversight of DURC, along with Institutional oversight is aimed at preserving the benefits of life sciences research while minimizing the risk that knowledge, information, products, or technologies generated by such research could be used in a manner that results in harm.

Additional information is requested for review purposes if any of the dual use categories are answered “Yes”.  PIs will only fall under DURC review if their research involves any of the 15 agents of concern and produces, aims to produce, or can be reasonably anticipated to produce one of the effects listed in the dual use categories.  Additional oversight will be required for such research. 

V. Job responsibilities for UI Staff

Describe in detail the roles and responsibilities of UI staff involved in handling/manipulating the recombinant material. The IBC will use this information to determine whether the individuals are appropriately trained and can carry out the duties of their assigned roles or if additional training must be provided to staff.  Should additional training be required, the IBC will ensure those individuals performing the training have the appropriate experience and knowledge to do so.

Depending on the research proposed, examples include:

  • Technical staff at DeGowin Blood Center, who has completed the BBP annual training will draw patients’ blood and ship to company X. Recombinant modifications will be done by company X and samples shipped to UIHC and administered by the nursing staff.
  • Ms. X, Study Coordinator, has worked in patient clinics for 40 years and will be responsible for preparing regulatory documents.
  • Ms. X, Pharmacist, has 20 years’ experience and will be responsible for maintenance of the research drug inventory and dispensing to the operating room.

W. Appendix M-I-A Protocol Submission Requirements

Additional requirements have been established for rDNA research involving human research participants. In accordance with the requirements stated in Appendix M of the NIH Guidelines, the PI is also required to submit the research protocol along with the required documentation to NIH OSP (Office of Science Policy).  The IBC will review information contained within Appendix M-I-A submission requirements, in addition to the investigator’s brochure and the rDNA Registration Document prior to approval.

NIH Guidance on Informed Consent for Gene Transfer Research is also available for those involved in this area of research.

X. Animal use

Administration of recombinant or synthetic nucleic acids or recombinant organisms to animals must be registered.  Such research would include plasmid or viral vectors directly administered to animals and/or stably transfected cell lines or recombinant organisms (i.e. recombinant bacteria) which are created and then subsequently administered to animals. 

If introduced into animals, list Animal Protocol number(s) in the text box, one per line, and include the species of the animal involved in the project.  Multiple species may be added if necessary, by clicking the Add Species button.

Describe the nucleic acids, vectors and/or recombinant organisms that will be administered to the animals and how they will be administered (route of administration). 

Depending on the research proposed, examples include:

  • Recombinant AAV will be injected into the mice either by IV or ID in the ear pinna.
  • Recombinant Listeria species expressing protein X will be administered into mice intranasally.
  • Mouse hematopoietic cells transduced with recombinant AAV will be introduced via IV.

The information listed in this section must include research that is also described  in the Animal Protocol.  Additional research can be registered with the IBC; however, the IACUC is not allowed to approve any additional procedures not approved by the IBC.  Should additional routes or vectors be listed in an Animal Protocol or Hazard Containment Form, the research will not be approved until an rDNA Registration Document or amendment request containing the additional route(s) or vector(s) has been reviewed and approved by the IBC.

Y. Generation of transgenic/knockout animals

Rodents:

Generating new strains utilizing recombinant DNA techniques must be registered with the IBC.  Describe the genetic alterations that will be made to the animal within the text box provided.

Generating a new strain of rodents via breeding may be exempt from the NIH Guidelines.  According to Appendix C-VII , breeding of two different transgenic rodents or the breeding of a transgenic rodent and a non-transgenic with the intent of creating a new strain of transgenic rodent that can be housed at BSL1 containment will be exempt from NIH Guidelines if:

  1. Both parental rodents can be housed under BL1 containment; and
  2. Neither parental transgenic rodent contains the following genetic modification (i) incorporation of more than one-half of the genome of an exogenous eukaryotic virus from a single family of viruses; or (ii) incorporation of a transgene that is under the control of a gammaretroviral long terminal repeat (LTR); and
  3. The transgenic rodent that results from this breeding is not expected to contain more than one-half of an exogenous viral genome from a single family of viruses.

For example, creating a double knockout mouse generated by cross breeding existing single knockout lines, housed in ABSL1 containment, would be exempt and not require IBC registration.

In addition, the purchase or transfer of transgenic rodents for experiments that require ABSL1 containment is exempt and does not require registration with the IBC.

Non-rodents:

Generating new strains utilizing recombinant DNA techniques or breeding existing lines must be registered with the IBC.  In addition, the purchase or transfer of genetically modified non-rodent animals must also be registered with the IBC as this is not exempt from the NIH Guidelines.  Describe the genetic alterations that will be made to the animal within the text box provided.

Depending on the research proposed, some examples of transgenic/knockout animal work include:

  • Transgenic pigs overexpressing human protein X will be generated by Company Y, from where it will be purchased.
  • Transgenic mice overexpressing HMGA2 will be generated.
  • Point mutations will be introduced to knockout function of gene X in mice.

Z. Determining Classification

Using the descriptive information provided, please select the appropriate classification for your project. Depending on the classification of the research, the level of oversight and the agencies/committees that must approve the research, as outlined in the description, will vary.

For a full description of the type of research covered by each classification, please see NIH Guidelines

AA.  Protocol Summary Page

Various action items for each rDNA Registration Document are available from the protocol summary page.  Clicking on the blue Action icon to the right of the table will bring up various actions that can be performed.  The available actions depend on the status of the protocol in the review process.

  • View:  This action allows a user to view all sections of the rDNA Registration Document with read-only access. A printable pdf may also be produced by accessing the document using this action and clicking the PDF icon at the bottom of a section. The PDF created however, will not contain documents that are attached to the rDNA Registration Document.
  • Compare:  This action allows a user to compare the most recent version of the rDNA Registration Document to a previous version (draft, approved, etc.). This action may be useful for determining what changes have been made during IBC review or an amendment proposal.
  • Edit:  This action allows an authorized user to make and save edits to any section of the rDNA Registration Document or amendment currently in draft or revision status.
  • Copy:  This action allows an authorized user to start a new rDNA Registration Document by copying the majority of an existing rDNA Registration Document for the purpose of submitting a new rDNA Registration Document. All sections will be copied, except for certain information including protocol number, health considerations, and dual use information). All appropriate edits may then be made in the newly created rDNA Registration Document prior to submission for IBC review.
  • Withdraw:  This action allows an authorized user to withdraw a submitted rDNA Registration Document or Amendment currently under IBC review. Withdrawing a submitted document will remove it from the review process entirely.
  • Renew:  This action allows an authorized user to start a renewal rDNA Registration Document from the currently approved version of an rDNA Registration Document for the purpose of continuing the same project. All pertinent information (including health considerations and dual use information) will be transferred to the new draft. All appropriate edits may then be made in the newly created renewal rDNA Registration Document prior to submission for IBC review.
  • Amend:  This action allows an authorized user to begin a draft amendment to an approved rDNA Registration Document. This action is only available on an approved document for which an amendment is not currently in draft or under IBC review. Any number of modifications can be made in a given amendment request; however, only one amendment request can be initiated/in review at a time.
  • Delete:  This action allows an authorized user to permanently delete a draft version of an rDNA Registration Document or amendment. Once an rDNA Registration Document or amendment is under IBC review, it cannot be deleted without first being withdrawn.  This action cannot be reversed.
  • Workflow:  This action allows an authorized user to see the workflow history of this rDNA Registration Document; the dates of submission, approval, and the review process can be viewed

AB.  Amendment Summary Field

Provide a brief summary of the purpose of the rDNA Registration Document amendment to be submitted.

Depending on the amendment proposed, some examples include:

  • Two new lab members have been added to this rDNA protocol.
  • Additional routes of administration into mice (intraperitoneal and subcutaneous) have been included.
  • An updated table containing new inserts has been attached.

AC. New Vector, Genetic Material or Delivery Methodology

The IBC must render an opinion on whether or not the submitted protocol meets this criterion.  The PI must elaborate on why s/he feels the criterion is or is not met. 

In cases where the protocol does NOT use a new vector, genetic material, or delivery methodology, please reference other published studies documenting use in human subjects.  References to studies available in the Genetic Modification Clinical Research Information System (GeMCRIS) are also appropriate.  The IBC will use this information to establish that the risk to subjects is clearly understood.

AD. Preclinical Safety Data

The IBC must render an opinion on whether or not the submitted protocol meets this criterion.  The PI must elaborate on why s/he feels the criterion is or is not met. 

In cases where the protocol does NOT rely on collecting preclinical safety data through a new preclinical model system, please describe the model system used to obtain the safety data and how it reliably establishes the risk to the subjects participating in the protocol.  Published studies utilizing this model system should also be referenced.

AE. Possible Toxicities

The IBC must render an opinion on whether or not the submitted protocol meets this criterion.  The PI must elaborate on why s/he feels the criterion is or is not met.

In cases where the protocol is NOT associated with possible toxicities that are not widely known or that are difficult to evaluate, please elaborate on how any toxicity related to the recombinant product was evaluated and tested.  Prior use of the vector/gene construct and/or delivery method in human and/or animal toxicity studies should be provided, if available.  References to studies available in the Genetic Modification Clinical Research Information System (GeMCRIS) are also appropriate. The IBC will use this information to establish that any possible toxicities relating to the product is understood.

AF. Appendix M-I-A Requirements

The following information must be submitted to the IBC and subsequently to NIH/OSP:

  • The scientific abstract.
  • The proposed clinical protocol, including tables, figures, and any relevant publications.
  • Summary of preclinical studies conducted in support of the proposed clinical trial or reference to the specific section of the protocol providing this information.
  • A description of the product:
    • Describe the derivation of the delivery vector system including the source (e.g., viral, bacterial, or plasmid vector); and modifications (e.g., deletions to attenuate or self-inactivate, encapsulation in any synthetic complex, changes to tropisms, etc.). Please reference any previous clinical experience with this vector or similar vectors.
    • Describe the genetic content of the transgene or nucleic acid delivered including the species source of the sequence and whether any modifications have been made (e.g. mutations, deletions, and truncations). What are the regulatory elements contained in the construct?
    • Describe any other material to be used in preparation of the agent (vector and transgene) that will be administered to the human research subject (e.g., helper virus, packaging cell line, carrier particles).
    • Describe the methods for replication-competent virus testing, if applicable.
    • Describe the intended ex vivo or in vivo target cells and transduction efficiency.
    • Describe the gene transfer agent delivery method.
  • The proposed informed consent document(s).
  • Specifically for submission to the NIH/OSP, the Principal Investigator shall provide additional documentation originating from oversight bodies involved in the review at an initial site(s) regarding their assessment of whether public RAC review is warranted. In the event that review is requested, a justification that one or more of the NIH RAC review criteria (see Section III-C-1) are met shall be included.

AG. NIH Protocol Registration Documentation

The PI must first register their clinical trial protocol with the local IBC and IRB instead of first submitting the protocol to the Recombinant DNA Advisory Committee (RAC).  The IBC and IRB will then collaboratively render opinions on whether the protocol meets one or more of three pre-defined criteria listed under the “Project Details” section of the protocol.  If one or more of these three criteria are met, the IBC and/or IRB will request full RAC review.  Letters will be sent to the PI outlining the results of these reviews. 

The PI must then submit the letters from the IBC and IRB, along with additional information as outlined in Appendix M-I-A, to the NIH/OSP.  Even if a protocol does not meet any of the three criteria, the NIH Director may select it for full RAC review if s/he determines that it presents significant scientific, societal, or ethical concerns.  NIH/OSP will send an acknowledgement to the PI that the protocol registration process is complete if no public RAC review is requested.  Otherwise, the protocol will be reviewed at a regularly scheduled meeting of the RAC and a letter summarizing the RAC’s comments and recommendations (if any) will be sent to the PI; receipt of this letter concludes the protocol registration process.

The acknowledgement of NIH protocol registration or letter outlining any RAC comments/recommendations must be forwarded to the IBC (ehs-rdna@uiowa.edu); Biosafety staff in EHS will upload the document to the appropriate rDNA protocol following receipt.  Final IBC approval may be granted only after the NIH Protocol Registration process or RAC review is complete.  Final IRB review and approval will follow IBC approval.