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. 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 Dr. Andrew Maksymowych, Institutional Biosafety Officer.

Registration is through Penn IBC Electronic Registration System (PIERS). Dr. Andrew Maksymowych must be listed as the IBC 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. Clinical Protocol
4. Investigator’s Brochure(s)
5. Penn-specific Informed Consent Document(s)
6. Pharmacy Manual
7. 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 approval 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. 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 without 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 formal amendment in PIERS. The updated ICF will be administratively reviewed and approved. After read into the committee meeting minutes, the status of the registration will change to “Approved”. Letter sent after read into committee meeting minutes. As a courtesy, an approval letter will be sent to the PI. Study activities under the revised documents may continue without confirmation of formal IBC approval.

All Personnel Changes

Personnel changes must be made through a formal amendment in PIERS. After administrative review and approval for standalone personnel changes, the status of the registration will change to “Approved”. As a courtesy, an acknowledgement letter will be sent to the PI.

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. 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. A copy of the registration approval letter will be forwarded to the IRB.

All Reportable events (SAEs) and adverse event documentation

All reportable evens and adverse event documentation must be sent directly to Dr. Andrew Maksymowych (amaks@ehrs.upenn.edu). The email MUST include the IBC number. 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, Closure requests, Continuing review submissions to IRB, Deviations, DSMP submission or revision, DSMB meeting minutes, Enrollment closures, Exception requests, IND transfer letters, Investigator’s brochure revisions, Study holds and resumptions, etc.

The IBC is not tasked with review and approval of attendant materials. An acknowledgement and/or approval letter will NOT be provided.

• 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)

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)

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 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, ICF, and personnel
• All 3-year registration renewals (a new IBC number will also be issued)

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 (status available in PIERS)
• Continuing review submissions to IRB
• Deviations
• DSMB meeting minutes
• 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 and revisions are formally reviewed by the IBC? The IBC will review amendments and revisions related to changes in the following:

• Clinical protocol
• ICF

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 without confirmation of formal IBC approval.

What IBC registration amendments and revisions 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:

• Personnel
• ICF (without changes to the clinical protocol)

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

What IBC registration amendment and revisions are not formally reviewed by the IBC? While Penn IBC requests submission of all attendant materials for registered studies, it is not tasked with review and approval of these materials. An acknowledgement and/or approval letter will NOT be provided. This includes the submission of the following material:

• Administrative Letters
• Closure Requests (status available in PIERS)
• Continuing review submissions to IRB
• Deviations
• DSMB meeting minutes
• 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

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.

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
• ICF
• Personnel

What revisions and/or additions can be made through administrative updates (without a formal amendment) to my approved IBC registration in PIERS? All administrative updates must be submitted as a "Registration Event" through the online registration. The following revisions and/or additions may be made through administrative updates to your approved IBC registrations:

• Administrative Letters
• Closure Requests
• Continuing review submissions to IRB
• Deviations
• DSMP submission or revision
• DSMB meeting minutes
• Enrollment closures
• Exception requests
• IND transfer letters
• Investigator’s brochure revisions
• IRB annual review submissions
• Study holds & Resumptions
• Reportable events (SAEs) and adverse event documentation