The SI assumes all responsibilities toward co-investigators that are normally assigned to the sponsor and is responsible for maintaining aneffective IND with respect to the investigations. These responsibilities include:
Once the IND is submitted and becomes effective, the SI must report the following information to the FDA
Once the IND is in effect, the SI must submit a new protocol amendment to the FDA for any new or modified protocol not contained in the IND application.
The modification should include the new or modified protocol as well as documentation that the protocol amendment was submitted to the FDA and the date of submission. The study may not begin until the new protocol has been reviewed and approved by the FDA and the IRB.
UI IRB policy
If the SI submits a new protocol to his/her IND application, the IRB expects that the IND holder maintain one IRB application that contains the entirety of the IND application and includes a full history of the initial submission and all amendments that are submitted to the FDA.
Each ancillary study to be conducted at the UI should be submitted in a separate IRB application, include the required IND information relevant to the ancillary study only and reference the IRB ID# of the main IND study in Section I.4.
All amendments must also be submitted to, reviewed and approved by the IRB before implementation.
Protocol amendments are necessary when a sponsor wants to change a previously submitted protocol or add a study procedure not submitted in the original IND.
The following protocol changes must be submitted to the FDA.
The addition of a new investigator must be reported to the FDA within 30 days of the investigator being added. Once the investigator is added to the study, the investigational drug may be shipped to the investigator and s/he may begin participating in the study.
There is no set schedule for FDA review of protocol amendments; each review is dependent on the reviewer’s workload. Therefore, the sponsor should contact the FDA project manager assigned to the IND to ascertain the review status of each amendment prior to implementation.
Any essential information that is not included in a protocol amendment, IND safety report, or annual report must be submitted to the FDA. Examples of essential information include:
When several submissions of new protocols, or protocol changes are anticipated in a short period, the sponsor is encouraged to include these in a single submission.
Definitions that apply to IND safety reporting requirements
FDA regulations require that sponsors make the causality assessment, based on information received from investigators; and indicates that the sponsor should consider both the investigator’s and the sponsor’s assessment when determining if an event is serious.
Why are IND safety reports required?
To ensure the timely communication of significant new information about experiences with the investigational drug. Findings that suggest a significant risk would ordinarily result in a safety-related change in the protocol, ICD, IB or the conduct of the study (e.g., result in a protocol amendment).
To whom are they submitted?
How should they be reported?
What should be reported and when?
UI IRB policy [6]
The following events are considered reportable per UI policy and must be reported to the IRB via the Reportable Event Form (REF) in HawkIRB.
The SI must submit an annual progress report to the FDA within 60 days of the anniversary date that the IND went into effect. This is the date the FDA permitted the study to begin and can be found on the FDA IND Acknowledgement Letter. The expected contents of the progress report are included in the hyperlink above.
If the due date of the annual report does not coincide with the date the IRB Continuing Review is due, the SI should describe in the first Continuing Review (CR) application that the annual report is not yet due, but the annual report will be attached at the time of the next Continuing Review. The annual report should be included on the Continuing Review Attachment category of the IRB Continuing Review form at the time of the next Continuing Review (CR). An annual report should be attached to all subsequent CRs.
Sponsor-investigators must inform the FDA of the desire to withdraw an IND. All clinical investigations conducted under the IND must cease, all current investigators must be notified and all of the study drug must be returned to the sponsor or otherwise disposed of at the request of the sponsor per 21 CFR 312.58 [10].
Any changes to financial disclosure information must be promptly reported to the FDA during the investigation and for 1 year following completion of the study. This information does not need be reported to the IRB.
The responsible party should update their records within 30 days of a change to the recruitment status, or completion date. Other changes or updates to the record, such as protocol amendments, must be made at least every 12 months.
In general, results of an applicable clinical trial of a drug or biologic that is approved, licensed, or cleared by FDA must be submitted by the sponsor no later than 12 months after the primary completion date [13].
The SI is responsible for maintaining the following records.
Accurate records documenting the receipt, shipment, or other disposition of the investigational drug. These records are required to include, as appropriate, the name of the investigator to whom the drug is shipped, and the date, quantity, and batch or code mark of each such shipment.
Documentation of any financial interests of any of the participating investigators involved in the study (see also 21 CFR 54 [14]). The sponsor-investigator is responsible for ensuring all participating investigators provide the SI with sufficient accurate financial information to allow the SI to submit complete and accurate certification or disclosure statements. The SI shall promptly update this information if any relevant changes occur during the course of the investigation and for 1 year following the completion of the study.
The FDA requires that the aforementioned records must be maintained: [21CFR 312.57(c) [11]]
The SI must allow FDA employees access to all records and reports at their request. Drug Enforcement Administration and Department of Justice employees must be given access to records and reports involving controlled substances at their request.
Links:
[1] http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?fr=312.53
[2] http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?fr=312.59
[3] http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?fr=312.30
[4] http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?fr=312.31
[5] http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?fr=312.32
[6] https://hso.research.uiowa.edu/ui-investigator%E2%80%99s-guide
[7] https://hso.research.uiowa.edu/ui-investigator%E2%80%99s-guideirb-standard-operating-procedures
[8] http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?fr=312.33
[9] http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?fr=312.38
[10] http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?fr=312.58
[11] http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?fr=312.57
[12] https://clinicaltrials.gov/ct2/manage-recs/fdaaa#WhichTrialsMustBeRegistered
[13] https://prsinfo.clinicaltrials.gov/definitions.html#PrimaryCompletionDate
[14] http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?CFRPart=54