Regulatory Open Forum

This message was posted by a user wishing to remain anonymous


Hello, 

I have a few questions regarding addressing the following for Annual IND Reports: "A summary of any significant manufacturing or microbiological changes made during the past year. "

1. What format should this be presented in and what information should be provided i.e. date implemented, rationale for change? 

2. Does information on ongoing and completed stability studies need to be included and if so, how much detail is needed and what format is preferred?

Thank you in advance for you help!

 

This message was posted by a user wishing to remain anonymous

All the cmc amendments that were submitted during the past IND annual reporting period should be tabulated:

Date of submission, serial number etc, Descriprion of change 

Rationale for change and implementing dates etc should have been described in the CMC amendments that were already submitted during the reporting year!
There are no annual reportable changes for IND only for NDA/BLAs. When a cmc change is made, you submit an amendment to the IND right away. In the AR, you only summarize the past amendments that were submitted like in the above format. Updated Stability data could be submitted at IND AR. Dont wait for AR to submit any CMC changes. CMC changes must be submitted to the IND as they happen as CMC amendments!!!
Original Message:
Sent: 23-Jul-2021 11:35
From: Anonymous Member
Subject: IND Annual Report - Manufacturing Changes

This message was posted by a user wishing to remain anonymous


Hello,

I have a few questions regarding addressing the following for Annual IND Reports: "A summary of any significant manufacturing or microbiological changes made during the past year. "

1. What format should this be presented in and what information should be provided i.e. date implemented, rationale for change?

2. Does information on ongoing and completed stability studies need to be included and if so, how much detail is needed and what format is preferred?

Thank you in advance for you help!

 

1) I don't think the format matters overmuch, though a table is certainly an efficient approach. A brief description of the change and a reference to the information amendment at least should be provided. (If it's a significant change, then there should have been an information amendment.)

2) Any stability data that has been generated since the last submission should be updated in the annual report (per the guideline on CMC information for Phase 2 & 3 studies). We also generally include a high-level summary of the data so far: no OOS/OOT results; no trends observed/no unexpected trends; data supports shelf life of XXX. It doesn't have to be super-detailed unless something unexpected occurred. For the summary, there isn't really a specific format; we just write a short paragraph. There is a recommended format for stability tables in the Phase I IND guideline.

I have to disagree with the statement from the previous reply that there are no annual reportable changes for INDs. There are some examples provided in the guideline on CMC information for Phase 2 & 3 studies, such as changes to the container closure system for the DS or DP if there is no impact on product quality. But it is true that most CMC changes during development require either an information amendment or are not reportable.

------------------------------
Rachel Thornton
Associate Director
Smyrna GA
United States
------------------------------

Original Message:
Sent: 23-Jul-2021 11:35
From: Anonymous Member
Subject: IND Annual Report - Manufacturing Changes

This message was posted by a user wishing to remain anonymous


Hello,

I have a few questions regarding addressing the following for Annual IND Reports: "A summary of any significant manufacturing or microbiological changes made during the past year. "

1. What format should this be presented in and what information should be provided i.e. date implemented, rationale for change?

2. Does information on ongoing and completed stability studies need to be included and if so, how much detail is needed and what format is preferred?

Thank you in advance for you help!

 

This message was posted by a user wishing to remain anonymous

"But it is true that most CMC changes during development require either an information amendment or are not reportable."

The above is correct for development INDs. The previous anonymous said the same thing! 
Original Message:
Sent: 25-Jul-2021 16:55
From: Rachel Thornton
Subject: IND Annual Report - Manufacturing Changes

1) I don't think the format matters overmuch, though a table is certainly an efficient approach. A brief description of the change and a reference to the information amendment at least should be provided. (If it's a significant change, then there should have been an information amendment.)

2) Any stability data that has been generated since the last submission should be updated in the annual report (per the guideline on CMC information for Phase 2 & 3 studies). We also generally include a high-level summary of the data so far: no OOS/OOT results; no trends observed/no unexpected trends; data supports shelf life of XXX. It doesn't have to be super-detailed unless something unexpected occurred. For the summary, there isn't really a specific format; we just write a short paragraph. There is a recommended format for stability tables in the Phase I IND guideline.

I have to disagree with the statement from the previous reply that there are no annual reportable changes for INDs. There are some examples provided in the guideline on CMC information for Phase 2 & 3 studies, such as changes to the container closure system for the DS or DP if there is no impact on product quality. But it is true that most CMC changes during development require either an information amendment or are not reportable.

------------------------------
Rachel Thornton
Associate Director
Smyrna GA
United States

Original Message:
Sent: 23-Jul-2021 11:35
From: Anonymous Member
Subject: IND Annual Report - Manufacturing Changes

This message was posted by a user wishing to remain anonymous


Hello,

I have a few questions regarding addressing the following for Annual IND Reports: "A summary of any significant manufacturing or microbiological changes made during the past year. "

1. What format should this be presented in and what information should be provided i.e. date implemented, rationale for change?

2. Does information on ongoing and completed stability studies need to be included and if so, how much detail is needed and what format is preferred?

Thank you in advance for you help!