I. Introduction
Per NIH Guidelines Section III-C, human gene transfer (HGT) is the deliberate transfer into human research participants of either:
- Recombinant nucleic acid molecules, or DNA or RNA derived from recombinant nucleic acid molecules, or
- Synthetic nucleic acid molecules, or DNA or RNA derived from synthetic nucleic acid molecules, that meet any one of the following criteria:
- Contain more than 100 nucleotides; or
- Possess biological properties that enable integration into the genome (e.g., cis elements involved in integration); or
- Have the potential to replicate in a cell; or
- Can be translated or transcribed.
Human gene transfer studies require approval from the Institutional Biosafety Committee (IBC), the Institutional Review Board (IRB), and potentially other institutional approvals prior to opening for enrollment at UCLA.
iii. IBC Submission in SafetyNet
When submitting an application to the UCLA IBC, the following documentation must be submitted in SafetyNet for review.
|
Document |
Additional Information |
| Curriculum vitae of PI and co-PI(s) | |
| Clinical Protocol | |
| Investigator's Brochure | Explain if not applicable. |
| Informed Consent Forms(s) | Must be site-specific. Draft version acceptable. |
| Pharmacy Manual (if available) | |
| SOPs for all procedures involving the HGT product, including product handling, transport, administration, and disposal | Must be site-specific and follow this HGT SOP Template. |
|
Bloodborne Pathogen Exposure Control Plan (if study involves collection of clinical specimens or delivery of materials covered under the Cal/OSHA BBP Standard) |
For non-Health Systems locations, complete the BBP Exposure Control Plan template. |
|
Aerosol Transmissible Disease Exposure Control Plan (if study involves aerosol transmissible diseases or pathogens) |
ATD Exposure Control Plan template |
II. Post-Approval Reporting Requirements
After initiation of an approved HGT Study, the following information and documents need to be submitted to the UCLA IBC (and any other applicable agencies/committees).
- Incidents (Biosafety-Related)
- Reporting Requirements Summary Sheet for further information on what, when and how to report this information.
- Changes that Could Impact the Biosafety Risk Assessment
Any changes that could potentially impact the initial biosafety risk assessment need to be submitted to the IBC for review prior to initiating these changes by creating an amendment in SafetyNet. This may include, but is not limited to:- Changes to the gene transfer product,
- Changes to the dosing route, dosage or dosing schedule of the gene transfer product
- Changes to the inclusion/exclusion criteria,
- Changes to any procedures involving handling the gene transfer product,
- Changes to the locations where the gene transfer product will be handled, stored, administered, etc.,
- Changes to the personnel who will handle, transport, or administer the gene transfer product or specimens collected from subjects,
- Any new safety information related to the gene transfer product,
- Changes in preconditioning and pre- and/or post-delivery concomitant medications,
- Changes in the monitoring/surveillance tests and/or procedures, and
- Changes to the Informed Consent Documents related to the gene transfer product.
The following information and documents DO NOT need to be submitted to the IBC after initiation of an approved HGT Study:
- Changes in the number of subjects enrolled in the study,
- Changes in the statistical analysis,
- Changes to staff that will be consenting subjects (if they will not be handling the gene transfer product or other materials)
III. Study Closure and Long Term Follow-up
A study may be closed in SafetyNet (submit a Closure Request) if the criteria listed below have been met. Additionally, new studies which look at long-term follow-up of subjects previously enrolled in an HGT study do not need to be submitted to the IBC if the criteria listed below have been met.
- The study is closed to enrollment,
- Subjects are not actively being dosed with recombinant materials
- There is no gene transfer product on site[a]
- It has been over a year since the last subject’s last dose, with no intention to dose further
- Samples are not being collected from the subjects[b], and
- The recombinant gene transfer product is not anticipated to persist in subjects >1 year post-administration such that it may pose a risk of horizontal [or vertical] transmission of recombinant materials to others.
[b] If long-term follow-up involves collection of clinical specimens, there would still need to be a BUA in place to cover the Bloodborne Pathogen exposure risks; however, the IBC would not need to review all of the documentation associated with the study. Additionally, IRB approval may still be required. Please consult with UCLA OHRPP to discuss IRB requirements.