Human gene therapy and clinical trials involving recombinant or synthetic nucleic acid molecules are becoming increasingly more common on medical research campuses, including here at the University of Kentucky (UK). Being among the cutting edge of medical research, these trials sometimes involve materials and techniques that fall under both federal and institutional regulations, in addition to those of the US Food and Drug Administration (FDA) and UK Institutional Review Board (IRB).
Clinical studies utilizing the biohazardous materials described below require registration with the UK IBC.
Investigational products (IP/IMP/Study Agent) that contain:
Note: If a study’s investigational product is not determined to require IBC registration, but patient samples are being sent to a research laboratory on UK’s campus for analysis and/or storage, please check with the Office of Biological Safety.
The University of Kentucky (UK) receives funding support from the National Institutes of Health (NIH). As a condition of NIH funding support, all work conducted at UK must comply with the NIH Guidelines, irrespective of the source of funding. As such, research subject to the NIH Guidelines must be registered with the UK IBC.
Human Gene Transfer (HGT) as defined by the NIH Guidelines can be found in Section III-C: Experiments Involving Human Gene Transfer that Require Institutional Biosafety Committee Approval Prior to Initiation.
Section III-C-1. Experiments Involving the Deliberate Transfer of Recombinant or Synthetic Nucleic Acid Molecules, or DNA or RNA Derived from Recombinant or Synthetic Nucleic Acid Molecules, into One or More Human Research Participants
Human gene transfer is the deliberate transfer into human research participants of either:
EXCEPTIONS - The following are NOT subject to the NIH Guidelines and DO NOT require UK IBC registration:
The United States Food and Drug Administration (FDA) Center for Biologics Evaluation and Research regulates cell therapy products, human gene therapy products, and certain devices related to cell and gene therapy.
Cellular therapy products include cellular immunotherapies, cancer vaccines, and other types of both autologous and allogeneic cells for certain therapy indications. Human gene therapy seeks to modify or manipulate the expression of a gene or to alter the biological properties of living cells for therapeutic use.
Cellular and gene therapy guidance documents are available from the FDA CBER online HERE.
Registration of a clinical study with the IBC requires the use of the tick@lab by a-tune web-based software located here. It is highly encouraged that you enlist the assistance of a member of the Biosafety Team when drafting a clinical IBC registration. This ensures that pertinent information is collected and listed on the registration appropriately, in a timely manner before going for review. Clinical/administrative staff delegated the task of completing the IBC registration form may experience some difficulties sufficiently completing areas of the form. It is important to note that per the NIH Guidelines, the PI (Principal Investigator) is ultimately responsible for all research activities, the information included in an IBC registration, and the complete and accurate disclosure of information for the purposes of the IBC registration. Registration guidance specific to clinical IBC registrations is outlined below.
When notified, a member of the Biosafety Team will guide you through and aid in the drafting of the registration. When navigating tick@lab by a-tune on your own, keep these helpful tips in mind for a successful experience. Please reference the How-To guides for navigating tick@lab by a-tune in our reference library, located here. Also, please ensure your internet connection is consistent and stable when utilizing the software, tick@lab by a-tune is a web browser-based software. Save your work often in tick@lab by a-tune, as there is not an “auto-save” feature.
An IBC registration & approval consists of a “cradle-to-grave” evaluation of the product and procedures, including but not limited to:
This information must be gathered by the PI/UK study team. Biosafety Team members are not responsible for the direct gathering of this information. The PI and study coordinators are responsible for gathering and providing required information to Biosafety Team members. It is the responsibility of the PI and study coordinators to contact the study sponsor as necessary, when additional information is required.
As the IBC registration form is completed, please take note of the help text provided on each question. Additionally, as some of the questions are completed, additional help text will appear with a response and provide additional guidance. This information is intended to assist the PI/authors of the registration in identifying the NIH Guidelines and other regulations that may apply to the proposed work in the registration. Always read all the form text in each question carefully and answer appropriately.
Be aware that the IBC registration form was created to be able to register all types of research involving potential biohazards, including studies with plant and animal research. Not all sections/questions may apply to the work proposed, but please keep in mind that the registration form cannot be submitted unless all questions are answered.
Here is a short checklist of information that will be required to begin the registration process of a new clinical IBC registration.
Before beginning to work in the registration system, please email a list of personnel (with linkblues) involved in the study to the Biosafety Team member you have been in contact with, or the Biosafety Office (biosafety@uky.edu). This information will be used to ensure personnel are available to be added to the IBC registration and for training verification. All personnel that would handle or otherwise come into contact with the investigational product or related patient samples (ex: UK Healthcare staff, pharmacy staff, shipping staff,) and the PI/Co-PIs, should be included in this list. If you will serve in an administrative-only role on the study (coordinator, regulatory staff, etc.), please note this in the IBC protocol registration. Anyone involved in an administrative-only role is not permitted to handle, transport, or ship investigational product or associated patient samples, related to the IBC registration.
All personnel handling or administering investigational product must be listed as personnel on the registration and complete required safety training. This may include but is not limited to individuals that:
Please check with your Biosafety Team member or the Biosafety Office for specific training requirements. Training guidance and frequency are referenced here. Required training is available on-demand online. Required training includes:
*There is no UK Healthcare substitution for Biological Safety Training.
**Personnel who have already completed UK Healthcare’s training WBT “Workplace Safety”, may provide a copy of this certificate in substitution for both the Chemical Hygiene Plan Laboratory Safety and Hazardous Waste training modules.
***Personnel who have already completed UK Healthcare’s training WBT “Bodily Fluid Exposure Bloodborne Pathogens” may provide a copy of this certificate in substitution for the Blood Borne Pathogens for Researchers module.
Please note that all required training must be completed before final IBC approval is issued.
An inspection, by the Office of Biological Safety, of all locations listed on the registration is required before final IBC approval may be issued. Attention will be paid to signage, available PPE, disinfection, disposal, facility conditions, and patient isolation from non-listed personnel or unenrolled participants. For clinics actively involved in patient care, an annual Clinical Biosafety Inspection can be scheduled and performed, to minimize disruption to operations and ongoing patient care throughout the year. A member of the Biosafety Team will coordinate these annual inspections with the heads of each clinical unit associated with an IBC registration.
All locations where the investigational product is stored, prepared, administered, or otherwise handled should be listed in the “Locations” section of the registration form. This would include the pharmacy location(s), patient treatment areas or clinics, and the UK Healthcare Cell Therapy Lab, as applicable. In addition to these areas, any specimen/tissue/biobank locations and academic research laboratories involved with the study should be listed. If patient samples will be processed in a CLIA-certified and inspected clinical laboratory within UK Healthcare, that location does not need to be included in this section, but please make a statement to this effect in the “Scientific Summary” section of the IBC registration.
If the clinical study being registered will be administered at a remote University site, please consult with the Biological Safety Officer.
The “Scientific Summary” free-text field of the IBC registration requires special attention. This section of the registration should provide IBC reviewers with all the details necessary to make an informed risk assessment. This should include pertinent study background information (including non-clinical and clinical study data), study plan, risks, mitigations, and site-specific details. Please do not simply paste the entire study document(s). While the information in the study documents is useful, some of it does not pertain to the biosafety considerations of the clinical study. The information provided should be specific to the biohazardous risk(s) of the study, the materials and procedures involved, and the mitigation steps employed to minimize risk.
Below is an outline of the sections and information of particular interest within the “Scientific Summary”:
The following documents should also be provided in the registration:
The PI is the only person allowed to perform the electronic signature and acknowledgment step to submit the IBC registration for review, via the “Sign & Submit” workflow within tick@lab by a-tune. These steps are detailed in all of the How-To Library documents and also outlined here.
Changes to the clinical study must be reflected in an amendment to the clinical IBC registration. Changes that necessitate an IBC amendment include, but are not limited to:
Instructions for the creation and submission of an IBC amendment are available in the How-To reference library, here. It is highly encouraged that you contact the Office of Biological Safety to assist you with any clinical IBC registration amendments.
IBC registrations are approved for a period of three (3) years. The clinical study’s PI and co-investigators will be contacted by the Office of Biological Safety well in advance of the IBC registration’s expiration. Please consult with a member of the Biosafety Team if you have questions or are uncertain about renewing your registration.
If a clinical study has concluded, an amendment to close the IBC registration may be submitted before the registration’s expiration date. Please consult with a member of the Biosafety Team if you wish to close your IBC registration.