Human Gene Transfer Protocols

Penn's Institutional Biosafety Committee (IBC) and the Institutional Review Board (IRB) must review and approve all human gene transfer and recombinant vaccine protocols prior to initiation of enrollment. All submissions must have an IND number through FDA approval. Investigational products that require IBC review and approval include, but are not limited to:

• T cells expressing Chimeric Antigen Receptor (CAR-T cells)
• Modified Biologics
• mRNA and DNA Vaccines
• Gene replacement therapy
• Viral vectors
• Oncolytic Viruses
• CRISPR/Cas9 and other Genome Editing Technologies

If you are unsure if your clinical protocol requires IBC review, please contact Amanda Wong, Assistant Biosafety Officer and IBC Administrator, at ajmwong@upenn.edu

Registration is through Penn IBC Electronic Registration System (PIERS). Dr. Andrew Maksymowych must be listed as the assigned Biosafety Officer in the Project Information Section. For help, please review the guidance documents:

How to Certify an HGT IBC Registration

How to Create a NEW HGT IBC Registration (In Development)

How to Initiate an Amendment to an Approved HGT IBC Registration

How to Submit Administrative Updates (Registration Events) in an Approved HGT IBC Registration (In Development)

How to Find my HGT IBC Approval Letter, Registration Status, and IBC Number (In Development)

The IBC must review IBC Registration-associated documents inclusive of the following HGT submissions:

New Human Gene Transfer Protocol IBC Registrations

The following material is required for submission to the IBC:

1. Completed PIERS Registration Form, certified by PI
2. IND Number
3. IRB Number
4. Clinical Protocol
5. Investigator’s Brochure(s)
6. Penn-specific Informed Consent Document(s)
7. Pharmacy Manual
8. Complete EHRS rsNA and Bloodborne Pathogen training or a health system training certificate
9. Other Study Communications from Sponsor (as available)

After review and approval of a NEW HGT protocol IBC registration, the status of the registration will change to “Approved”. As a courtesy, an electronic letter with the assigned IBC registration number will be sent to the PI. A copy of the registration approval letter will be forwarded to the IRB and research coordinator. Study enrollment MUST NOT begin until an FDA IND number has been issued and both IBC and IRB approvals are received.

All HGT Protocol Registration Amendments

Clinical protocol amendments (also submitted to IRB) and new versions of ICFs must be submitted to the IBC as a formal amendment in PIERS for review by the IBC. After review and approval of an HGT protocol registration amendment, the status of the registration will change to “Approved”. As a courtesy, an approval letter will be sent to the PI. Study activities under the revised documents may continue pending confirmation of formal IBC approval.

All Informed Consent (ICF) updates without modification to Clinical Protocol

Without modification to the clinical protocol, updated ICFs must be submitted to the IBC through a registration event in PIERS. The updated ICF will be administratively reviewed and accepted. After read into the committee meeting minutes, the status of the registration will change to “Accepted”. Study activities under the revised documents may continue without confirmation of formal IBC approval.

No approval or acknowledgement will be sent. All registration events accepted in PIERS will be viewable through the workflow feature.

All Personnel Changes

Personnel changes must be made through a registration event in PIERS. After administrative review and approval for standalone personnel changes, the status of the registration will change to “Accepted”. 

*PI changes must be sent as an amendment in PIERS. Once approved, a letter will be sent to the PI, the IRB, and research coordinator. 

All 3-year Registration Renewals

Formal submission is required through PIERS. If submitted before the expiration, study activities may continue uninterrupted. If the initial registration expires, the study is in violation of the NIH Guidelines. Clinical activities may continue but new enrollment must pause until renewal is approved by the IBC. After review and approval of a 3-year HGT protocol renewal IBC registration, the status of the registration will change to “Approved”. As a courtesy, an approval letter with the new assigned IBC registration number will be sent to the PI and research coordinator A copy of the registration approval letter will be forwarded to the IRB.

All Reportable events (SAEs) and adverse event documentation

All reportable events and adverse event documentation must be submitted as a registration event in PIERS. Upon administrative review, the documents will be added to most recent approved submission. An acknowledgement letter will not be provided.

The University of Pennsylvania IBC requests submission of all attendant materials for registered studies not limited to but including:

Administrative letters, Deviations, DSMB submission or revision, DSMB letters, Enrollment closures, Exception requests, IND transfer letters, Investigator’s brochure revisions, Study holds and resumptions, any events that directly impacts the study, etc.

 All materials must be submitted as a registration event in PIERS. 

The IBC is not tasked with review and approval of attendant materials. An approval letter will NOT be provided. Acknowledgement will be viewable in PIERS.

• Recombinant or Synthetic Nucleic Acid Guidelines - EHRS Training is required for all personnel listed on the registration every three years. 
• All personnel must complete training prior to registration or amendment review and approval.
• Recombinant or Synthetic Nucleic Acid Guidelines - EHRS Training is available online through Workday Learning and Knowledge Link (UPHS employees only)
• Bloodborne Pathogens V2 Training is available online through Workday Learning

A health system training certificate may be uploaded in PIERS to substitute the above training modules.

Failure to complete training will delay IBC review.

1. NIH Office of Science Policy (OSP) 
2. NIH Guidelines for Research Involving Recombinant & Synthetic Nucleic Acids
3. Institutional Biosafety Committee (IBC)
4. IBC Meeting Schedule and Submission Deadlines
5. Contact the Institutional Review Board (IRB) regarding submission of protocols for IRB review
6. The Office of Clinical Research at the Perelman School of Medicine, University of Pennsylvania supports all human research activities 

Who should be listed as personnel on the registration form? The following people must be listed as personnel on the registration form:

• The Principal Investigator
• Co-Investigators
• Clinical Research Coordinator(s)

*Persons providing standard care do not need to be listed on the registration.

What spaces should be listed in the IBC registration? The following space should be listed in the IBC registration:

• Study Site Location

To what section of the NIH Guidelines is my protocol subject? HGT studies are subject to Section III-C-1 of the NIH Guidelines (https://osp.od.nih.gov/wp-content/uploads/NIH_Guidelines.pdf): 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.

I just submitted an IBC registration for a protocol. When will it be reviewed by the IBC? IBC registrations are reviewed once a month on the scheduled meeting date. IBC registrations that have been submitted prior to the submission deadline and meet the criteria for IBC review (i.e., required documents have been included, training is complete, certification by the PI, etc.) will be reviewed at the next scheduled meeting. IBC registrations that do not meet the criteria for IBC review may be delayed in receiving review and approval.

What submissions will receive an approval letter? An approval letter will be issued to the PI, IRB, and research coordinator after IBC review and approval or administrative approval of the following submissions:

• New HGT Protocol IBC Registrations
• All HGT Protocol Registration Amendments made through PIERS including changes to the Clinical Protocol
• All 3-year registration renewals (a new IBC number will also be issued)
• Changes in Principle Investigator

What submissions will not receive an approval letter? You will not receive an approval or acknowledgement letter when the following material is submitted:

• Administrative Letters
• Closure Requests (Acknowledgment available in PIERS)
• Deviations
• ICF changes
• Personnel Changes 
• Attendant Material
• DSMB Letters
• DSMB submission or revision
• Enrollment closures
• Exception requests
• IND transfer letters
• Investigator’s brochure revisions
• Reportable events (SAEs) and adverse event documentation
• Study holds & Resumptions

What IBC registration amendments are formally reviewed by the IBC? The IBC will review amendments related to changes in the following:

• Clinical protocol

Note: After initial IBC approval, formal IBC approval of amendments and revisions to this material is not required to continue study activities under the revised documents. Study activities may continue pending confirmation of formal IBC approval.

What IBC registration amendments are administratively approved by the Institutional Biosafety Officer? The Institutional Biosafety Officer will administratively review and approve amendments and revisions related to changes in the following:

• Changes to Principle Investigator

Note: After initial IBC approval, formal IBC approval of amendment this material is not required to continue study activities under the revised documents. Study activities may continue without confirmation of formal IBC approval.

Are registration events formally reviewed by the IBC? No, while Penn IBC requests submission of all attendant materials for registered studies, the IBC is not tasked with review and approval of these materials. An approval letter will NOT be provided, acknowledgement will be viewable in PIERS. This includes the submission of the following material:

• Administrative Letters
• Deviations
• DSMB Letters
• DSMB submission or revision
• Enrollment closures
• Exception requests
• IND transfer letters
• Investigator’s brochure revisions
• Reportable events (SAEs) and adverse event documentation
• Study holds & Resumptions
• Any other attendant material

Do I need an IBC number and approval letter before I submit my protocol to the IRB? No, an IBC number and approval letter is not required when submitting the protocol to the IRB. IBC and IRB approval may be sought concurrently.

I am anxious to start protocol enrollment, but I have not received a formal IBC approval letter. When can I start enrolling patients? Patient enrollment may begin after the IBC registration has been approved. This status change is noted in the Workflow & History section of the PIERS registration form. Even though IBC approval is required, a formal IBC approval letter is not required to initiate enrollment.

Where can I find a copy of my IBC approval letter? A copy of the IBC approval letter is attached to the IBC registration in PIERS under the IBC Communications section.

Where can I find my IBC number? The IBC number can be found in the IBC registration in PIERS at the top of the page or any IBC correspondence sent to the PI and research coordinator.

What revisions and/or additions must be made through a formal amendment to my approved IBC registration in PIERS? The following revisions and/or additions must be made through a formal amendment in PIERS:

• Clinical protocols
• Changes to Principle Investigator

What registration events can be made through administrative updates (without a formal amendment) to my approved IBC registration in PIERS? 

• Administrative Letters
• Deviations
• DSMB submission or revision
• DSMB Letters
• Enrollment closures
• Exception requests
• IND transfer letters
• Investigator’s brochure revisions
• Study holds & Resumptions
• Reportable events (SAEs) and adverse event documentation