Regulatory Open Forum

Dear Regulatory community,

Looking for your wisdom for a Phase 3 NME study:

• Initial SAR was submitted as a SUSAR because the IB in effect at the time did not list this type of SAR in the RSI
• Follow-up was obtained after a new IB went into effect with does list the SAR as expected in the RSI

Questions:

1. Is the company required to continue submitting Follow-Up safety reports for the case, since it was unexpected at time of initial report?
2. Should the company submit one final Follow-Up safety report for the case indicating the expectedness criteria for the event type has changed and that any additional Follow-Up reports for this case will not be submitted as they no longer meet the criteria for expedited submission (I believe this is how a change from SAE to AE may be handled)?
3. Should the company stop submitting any Follow-Up safety reports as soon as the change in expectedness has been determined?
4. Or, does it depend on what the Safety Management Plan for the study says?

You guidance would be appreciated. The FDA guidance on Safety Reporting Requirements didn't offer any clear guidance.

Thanks!

Hello,

Investigational brochure is normally updated annually with new safety information. Any relevant SUSARs in the meantime are reported to the regulatory authorities. 

You need to submit follow up if the event no longer qualifies for submission.

Have a weekend.

Olga

Dear Regulatory community,

Looking for your wisdom for a Phase 3 NME study:

• Initial SAR was submitted as a SUSAR because the IB in effect at the time did not list this type of SAR in the RSI
• Follow-up was obtained after a new IB went into effect with does list the SAR as expected in the RSI

Questions:

1. Is the company required to continue submitting Follow-Up safety reports for the case, since it was unexpected at time of initial report?
2. Should the company submit one final Follow-Up safety report for the case indicating the expectedness criteria for the event type has changed and that any additional Follow-Up reports for this case will not be submitted as they no longer meet the criteria for expedited submission (I believe this is how a change from SAE to AE may be handled)?
3. Should the company stop submitting any Follow-Up safety reports as soon as the change in expectedness has been determined?
4. Or, does it depend on what the Safety Management Plan for the study says?

You guidance would be appreciated. The FDA guidance on Safety Reporting Requirements didn't offer any clear guidance.

Thanks!

Dear Regulatory community,

Looking for your wisdom for a Phase 3 NME study:

• Initial SAR was submitted as a SUSAR because the IB in effect at the time did not list this type of SAR in the RSI
• Follow-up was obtained after a new IB went into effect with does list the SAR as expected in the RSI

Questions:

1. Is the company required to continue submitting Follow-Up safety reports for the case, since it was unexpected at time of initial report?
2. Should the company submit one final Follow-Up safety report for the case indicating the expectedness criteria for the event type has changed and that any additional Follow-Up reports for this case will not be submitted as they no longer meet the criteria for expedited submission (I believe this is how a change from SAE to AE may be handled)?
3. Should the company stop submitting any Follow-Up safety reports as soon as the change in expectedness has been determined?
4. Or, does it depend on what the Safety Management Plan for the study says?

You guidance would be appreciated. The FDA guidance on Safety Reporting Requirements didn't offer any clear guidance.

Thanks!

Safety reporting guidance for SUSARs indicate that Follow-Up Safety Reports should be submitted when relevant additional information obtained by the sponsor that pertains to a previously submitted IND safety report must be submitted as a Follow-up IND Safety Report without delay, as soon as the information is available (§ 312.32(d)(2)). I agree that the guidance does not address the issue of when a SUSAR based on expectedness becomes expected when an updated IB is issued. However, I would take the position that a SUSAR, once submitted, is still a SUSAR until all relevant information is complete in FDA files.

Dear Regulatory community,

Looking for your wisdom for a Phase 3 NME study:

• Initial SAR was submitted as a SUSAR because the IB in effect at the time did not list this type of SAR in the RSI
• Follow-up was obtained after a new IB went into effect with does list the SAR as expected in the RSI

Questions:

1. Is the company required to continue submitting Follow-Up safety reports for the case, since it was unexpected at time of initial report?
2. Should the company submit one final Follow-Up safety report for the case indicating the expectedness criteria for the event type has changed and that any additional Follow-Up reports for this case will not be submitted as they no longer meet the criteria for expedited submission (I believe this is how a change from SAE to AE may be handled)?
3. Should the company stop submitting any Follow-Up safety reports as soon as the change in expectedness has been determined?
4. Or, does it depend on what the Safety Management Plan for the study says?

You guidance would be appreciated. The FDA guidance on Safety Reporting Requirements didn't offer any clear guidance.

Thanks!

Dear Regulatory community,

Looking for your wisdom for a Phase 3 NME study:

• Initial SAR was submitted as a SUSAR because the IB in effect at the time did not list this type of SAR in the RSI
• Follow-up was obtained after a new IB went into effect with does list the SAR as expected in the RSI

Questions:

1. Is the company required to continue submitting Follow-Up safety reports for the case, since it was unexpected at time of initial report?
2. Should the company submit one final Follow-Up safety report for the case indicating the expectedness criteria for the event type has changed and that any additional Follow-Up reports for this case will not be submitted as they no longer meet the criteria for expedited submission (I believe this is how a change from SAE to AE may be handled)?
3. Should the company stop submitting any Follow-Up safety reports as soon as the change in expectedness has been determined?
4. Or, does it depend on what the Safety Management Plan for the study says?

You guidance would be appreciated. The FDA guidance on Safety Reporting Requirements didn't offer any clear guidance.

Thanks!

IB is updated annually if nothing changes in RSI. In your case, the IB needs to be updated right away! This is a significant change in safety profile so it requires IB is updated right away.

Dear Regulatory community,

Looking for your wisdom for a Phase 3 NME study:

• Initial SAR was submitted as a SUSAR because the IB in effect at the time did not list this type of SAR in the RSI
• Follow-up was obtained after a new IB went into effect with does list the SAR as expected in the RSI

Questions:

1. Is the company required to continue submitting Follow-Up safety reports for the case, since it was unexpected at time of initial report?
2. Should the company submit one final Follow-Up safety report for the case indicating the expectedness criteria for the event type has changed and that any additional Follow-Up reports for this case will not be submitted as they no longer meet the criteria for expedited submission (I believe this is how a change from SAE to AE may be handled)?
3. Should the company stop submitting any Follow-Up safety reports as soon as the change in expectedness has been determined?
4. Or, does it depend on what the Safety Management Plan for the study says?

You guidance would be appreciated. The FDA guidance on Safety Reporting Requirements didn't offer any clear guidance.

Thanks!

As stated in the original post, the RSI was already updated (in the IB), thus the question relates to Follow-up information received after the update was implemented. Thanks.

IB is updated annually if nothing changes in RSI. In your case, the IB needs to be updated right away! This is a significant change in safety profile so it requires IB is updated right away.

Dear Regulatory community,

Looking for your wisdom for a Phase 3 NME study:

• Initial SAR was submitted as a SUSAR because the IB in effect at the time did not list this type of SAR in the RSI
• Follow-up was obtained after a new IB went into effect with does list the SAR as expected in the RSI

Questions:

1. Is the company required to continue submitting Follow-Up safety reports for the case, since it was unexpected at time of initial report?
2. Should the company submit one final Follow-Up safety report for the case indicating the expectedness criteria for the event type has changed and that any additional Follow-Up reports for this case will not be submitted as they no longer meet the criteria for expedited submission (I believe this is how a change from SAE to AE may be handled)?
3. Should the company stop submitting any Follow-Up safety reports as soon as the change in expectedness has been determined?
4. Or, does it depend on what the Safety Management Plan for the study says?

You guidance would be appreciated. The FDA guidance on Safety Reporting Requirements didn't offer any clear guidance.

Thanks!