Attachment 4a: Ad Hoc Reporting Requirements
The section below includes non–routine (Ad hoc) reporting requirements. These reports are event driven and are due contingent upon Such events occurring. All reports should be submitted to the CARB–X Chief of Research and Development., Additional report recipients are as indicated below.
1. Changes in the status of ongoing clinical study protocols:
a) Major Changes: Subrecipient must notify PTE within three (3) calendar days and provide copies of documents related to all major changes in the status of any ongoing clinical study protocols, including the following:
- All amendments or changes to the protocol, identified by protocol version number, date, or both, and dates it is valid
- All changes in informed consent documents, identified by version number, dates, or both, and dates it is valid
- Termination or temporary suspension of patient accrual
- Termination or temporary suspension of the protocol
- Any change in IRB approval
- Any other problems or issues that could affect the participants in the studies.
Notification of major changes should be by email to the CARB–X Chiefof Research and Development, followed by a letter signed by Subrecipient’s authorized business official, detailing notification of the change of status to the IRB and a copy of any responses from the IRB or IEC.
Major changes are those that:
- Alter the risk to benefit assessment
- Affect the safety of the subjects
- Add new medical, social, or psychological risks
- Significantly alter the design or scientific aims of the study
- Affect a subject’s willingness to continue participation in the study
b) All Changes: Subrecipient must submit a monthly report of all changes in the status of any ongoing clinical study protocols.
2. Required Time Sensitive Notifications: Under an IND or IDE, Subrecipient must provide FDA safety reports of serious adverse events. Subrecipient must submit copies of such FDA safety reports to PTE and BARDA as detailed below. Reports to PTE are to be submited to the CARB–X Chief of Research and Development. Reports to BARDA are to be submitted to and the clinical lead assigned by BARDA to the project team.
a) Expedited safety report of unexpected or life–threatening experience or death: A copy of any report of unexpected or life threatening experience or death associated with the use of an IND drug, which must be reported to FDA by telephone or fax as soon as possible but no later than seven (7) calendar days after the IND sponsor’s receipt of the information, must be submitted to PTE and BARDA within 24 hours of FDA notification.
b) Expedited safety reports of serious and unexpected adverse experience: A copy of any report of unexpected and serious adverse experience associated with use of an IND drug or any finding from tests in laboratory animals that suggests a significant risk for human subjects, which must be reported in writing to FDA as soon as possible but no later than 15 calendar days after the IND sponsor’s receipt of the information, must be submitted to PTE and BARDA within 24 hours of FDA notification.
c) IDE reports of unanticipated adverse device effect: A copy of any reports of unanticipated adverse device effect submitted to FDA must be submitted to PTE and BARDA within 24 hours of FDA notification.
d) Other adverse events documented during the course of the trial should be included in the annual IND or IDE report and reported to PTE and BARDA.
3. Incident Report
Subrecipient shall communicate and document all critical program concerns, risks, or potential risks with PTE.
- Due within 24 hours of activity or incident or within 12 hours for a security activity or incident.
- Email or telephone with written follow–up
- Additional updates within 24 hours of additional developments.
- Subrecipient shall submit within 3 business days a Corrective Action Plan (if deemed necessary by either party) to address any potential issues.
- If corrective action is deemed necessary, Subrecipient must address in writing, its consideration of concerns raised by PTE within 3 business days of receiving such concerns in writing.
4. FDA or EMA Audits
In the event of an FDA or EMA inspection which occurs that relates to products under this Subaward Agreement, or for any other FDA or EMA inspection that has the reasonable potential to impact the performance of this Subaward Agreement, Subrecipient shall provide PTE with an exact copy (non–redacted) of the FDA Form 483 and the Establishment Inspection Report (EIR) (or the corresponding forms from the EMA). Subrecipient shall provide PTE with copies of the plan for addressing areas of non– conformance to FDA or EMA regulations for GLP, GMP, or GCP guidelines as identified in the audit report, status updates during the plan’s execution and a copy of all final responses to the FDA or EMA
- Subrecipient shall notify PTE within 5 business days of a scheduled FDA or EMA audit or within 12 hours of an ad hoc site visit/audit if the FDA or EMA does not provide advanced notice.
- Subrecipient shall provide copies of any FDA or EMA audit report received from sub–recipients that occur as a result of this agreement or for products funded hereunder within three (3) business days of receiving correspondence from the FDA or EMA.
- Within five (5) business days of audit report, Subrecipient shall provide PTE with a plan for addressing areas of nonconfornmance, if any are identified.
- For the purposes of this Attachment 4a, “EMA” incudes all constituent national drug regulatory authorities.
The section below includes PTE Initiated non–routine [Ad hoc] reporting requirements. These reports are due three (3) business days after request. All reports should be submitted to the CARB–X Chief of Research and Development. Additional report recipients are as indicated below.
1. Final Reports for Clinical, Non–Clinical Studies, Manufacturing Campaigns. PTE may request that Subrecipient provide Clinical, Non–Clinical Studies, Manufacturing Campaigns, and other product development final reports to PTE for review and comment.
2. Standard Operating Procedures. PTE may request that Subrecipient shall make internal and subcontractor Standard Operating Procedures (SOPs) available for review electronically.
3. Regulatory Correspondence and Submissions. PTE may request that Subrecipient provide any regulatory correspondence (FDA, EMA, etc.) for products supported under this agreement.
4. QA Audits and Reports. PTE reserves the right to participate in QA audits at the Subrecipient. Upon completion of the audit/site visit the Subrecipient shall provide a report capturing the findings, results and next steps in proceeding. If action is requested of the Subrecipient, detailed concerns for addressing areas of non–conformance to FDA or EMA regulations for GLP, GMP, or GCP guidelines, as identified in the audit report, must be provided to PTE. The Subrecipient shall provide responses from the site to address these concerns and plans for corrective action execution.