FDA Submissions and Lifecycle Management

After an initial IND application is authorized by the FDA (also called receiving the “may proceed”) or an initial IDE application is approved by the FDA, the Sponsor is required to maintain a current application with the FDA. This section outlines ongoing and the final submission requirements. Refer to the WI Submitting to the FDA for details on how to submit. OCR Regulatory can assist you with templates, planners, and submission support. Please contact us at PSOM-IND-IDE@POBOX.upenn.edu.

For some studies, an individual might be both the PI and the (Regulatory) Sponsor. In this case, both sets of responsibilities mentioned apply.

Electronic submission is the preferred method for FDA IND submissions and a FDA form 1571 is always required (Form FDA 1571 and instructions).¹ Secure email communications with the FDA require use of PennMedicine email accounts.

The types of submissions required after the IND Application is authorized are summarized below² in the table, and more information can be found on the FDA Investigator-Initiated IND Applications webpage. Please contact OCR Regulatory for additional guidance via email at PSOM-IND-IDE@POBOX.upenn.edu.

IND Submissions^2,3	Description of Submission	Submission and/or Implementation Requirement Timeline
Protocol Amendment – New Protocol	When a sponsor intends to conduct a study that is not covered by a protocol already contained in their IND application.	Submission must occur prior to implementation
Protocol Amendment – Changes to a Protocol – Eliminate Immediate Hazard	Protocol change intended to eliminate an apparent immediate hazard to subjects	May be implemented immediately provided FDA is subsequently notified by protocol amendment
Protocol Amendment – Changes to a Protocol	Any change in a Phase 1 protocol that significantly affects the safety of subjects; or Any change in a Phase 2 or 3 protocol that significantly affects the safety of subjects, the scope of the investigation, or the scientific quality of the study.	Submission must occur prior to implementation
Protocol Amendment – New Investigator	When a new investigator is added to carry out a previously submitted protocol	Notification to FDA within 30 days of the investigator being added
Information Amendment	Essential information on the IND that is not within the scope of a protocol amendment, IND safety reports, or annual report.	Submitted as necessary but, to the extent feasible, not more than every 30 days
IND Safety Report – 15-day ⁴	Potential serious risks, from clinical trials or any other source or SUSAR (Suspected Unexpected Serious Adverse Reaction)	No later than 15 calendar days after the sponsor determines that the information qualifies for reporting
IND Safety Report – 7-day ⁴	Fatal or Life Threatening SUSAR	No later than 7 calendar days after the sponsor initial receipt of the information
IND Safety Report – Follow-Up ⁴	Any relevant additional information that pertains to a previously submitted IND safety report.	As soon as the information is available but no later than 15 calendar days after the sponsor receives the information.
Annual Report	Updates on the preclinical, manufacturing and clinical (all studies under the IND) sections of the IND and to its investigational plan	Within 60 days of the anniversary date that the IND went into effect (the “May Proceed” date).
Withdrawal of an IND	Once all protocols under the IND are ended. If the withdrawal is for safety reasons, the notification must provide a report of the reasons.	N/A

21 CFR §312.23.
NIH Clinical Center Regulatory Toolbox (IND Maintenance).
21 CFR §312.30, §312.31, §312.32, §312.33, §312.38.
Must be submitted on a MedWatch Form FDA 3500A (Form and instructions)

There are three types of full IDE maintenance submissions to the FDA: Amendments (A001, A002, etc.), Reports (R001, R002, etc.), and Supplements (S001, S002, etc.). These maintenance submissions¹ are summarized in the table below and more information can be located on the FDA website IDE Reports and IDE Modifications. Please contact OCR Regulatory for additional guidance via email at PSOM-IND-IDE@POBOX.upenn.edu.

IDE Submission Type ^2,3	Description of Submission	Submission and/or Implementation Requirement Timeline
Amendment – Response to Disapproval	N/A	Response date provided in FDA communication
Amendment – Response to Approval with Conditions	N/A	Response date provided in FDA communication
Amendment – Response to Refuse to Accept	N/A	Response date provided in FDA communication
Amendment – Response to Report Deficient	N/A	Response date provided in FDA communication
Amendment – Voluntary Withdrawal by Sponsor	If the IDE is not yet approved, the sponsor may request to withdraw the application	N/A
Report ^4,5 – Unanticipated Adverse Device Effects (UADE)	The sponsor must report the results of an evaluation of an unanticipated adverse device effect to FDA and all reviewing IRBs and investigators	Within 10 working days after the sponsor first receives notice of the effect
Report ^4,5 – Withdrawal of IRB approval	The sponsor must notify FDA and all reviewing IRBs and participating investigators of the withdrawal of IRB approval of an investigation (or any part of an investigation)	Within 5 working days after receipt of the withdrawal of approval
Report ^4,5 – Deviation from the investigational plan	Deviation does NOT affect validity of data/information; patient risk to benefit relationship; scientific soundness of plan; or rights, safety or welfare of subjects	In progress report
Report ^4,5 – Deviation from the investigational plan	Deviation does affect validity of data/information; patient risk to benefit relationship; scientific soundness of plan; or rights, safety, or welfare of subjects	Within 5 working days after receipt of the notice of deviation
Report ^4,5 – Failure to Obtain Informed Consent	Sponsors must submit a copy of any report by an investigator of the use of a device without first obtaining informed consent.	Within 5 working days after receipt of the notice of such use
Report ^4,5 – Current Investigators List	A current list of the names and addresses of all investigators participating in a significant risk device investigation.	Every six months
Report ^4,5 – Annual Progress Report	For a significant risk device, the sponsor must submit the progress report to FDA.	At least yearly.
Report ^4,5 – Interim Progress Report	N/A	If requested by FDA
Report ^4,5 – Recall/Repair/Dispose Device	The sponsor must notify FDA and all reviewing IRBs of any request that an investigator return, repair, or dispose of any unit of an investigational device.	Within 30 working days after request is made for an investigator to return, repair, or dispose of any unit of the device
Report ^4,5 – Completion or Termination of the Investigation/Final Report	The sponsor must notify FDA and all reviewing IRBs of the completion or termination of the investigation and submit a final report.	Notify FDA within 30 working days of the completion or termination of the investigation Submit final report to FDA within 6 months after completion or termination
Supplement ⁶ – Changes to the device or manufacturing process	A significant change in design or any change to the basic principles of operation or Affects validity of data/information; patient risk to benefit relationship; scientific soundness of plan; or rights, safety or welfare of subjects	FDA approval required prior to implementation
Supplement ⁶ – Changes to the device or manufacturing process	NOT a significant change in design/manufacturing or Does NOT affect validity of data/information; patient risk to benefit relationship; scientific soundness of plan; or rights, safety or welfare of subjects	Within 5 working days of implementation
Supplement ⁶ – Minor changes to the investigational plan (purpose of the study, risk analysis, monitoring procedures, labeling, informed consent materials, and IRB information)	If they do not affect the validity of the data, the scientific soundness of the investigational plan, or the rights, safety, or welfare of the human subjects involved in the investigation.	In progress report

Although original abbreviated IDE (aIDE) applications are not submitted to the FDA, there are some instances where FDA reporting is required as presented below. Please contact OCR Regulatory for additional guidance via email at PSOM-IND-IDE@POBOX.upenn.edu.

Required Reporting to the FDA	Description of Submission	Submission Timeline
Unanticipated Adverse Device Effect (UADE)	The sponsor must report the results of an evaluation of an unanticipated adverse effect to FDA and all reviewing IRBs and investigators.	Within 10 working days after the sponsor first receives notice of the effect
Withdrawal of IRB Approval	The Sponsor must notify FDA and all reviewing IRBs and participating investigators of the withdrawal of IRB approval of an investigation (or any part of an investigation).	Within 5 working days after receipt of the withdrawal of approval
Recall/Repair/Dispose Device	The sponsor must notify FDA and all reviewing IRBs of any request that an investigator return, repair, or dispose of any unit of an investigational device.	Within 30 working days of request
Failure to Obtain Informed Consent	The sponsor must submit a copy of any report by an investigator of the use of a device without first obtaining informed consent.	Within 5 working days after receipt of the notice of such use
Change in Risk by IRB	The sponsor must submit a change in the IRB assessed risk from nonsignificant risk (NSR) to significant risk (SR).	Within 5 working days after the sponsor first learns of the IRB's determination

FDA Submissions and Lifecycle Management

IND Submissions to the FDA

IDE Submissions to the FDA

Abbreviated IDE Submissions to the FDA