Regulatory Open Forum

Hello,

I am working on updating Module 3 sections for an IND as we are beginning Phase 3. This is a clinical-stage biotech and this is the DS and DP that will be used in registrational studies.
The documents I received from CMC for submission do not include version nor date. I would appreciate if others can comment if we should be including versioning and/or date. These documents are not in a controlled document management system. We receive Word documents from CMC and regulatory pdf's and publishes them. There is no formal approval/signature. 
Would it be sufficient to use a controlled DMS to capture formal review and approval? If so, would we still need to add version and/or date to the documents?
Thank you in advance for your advice.

Good morning, Anonymous.

I do a lot of late-stage Module 3 writing, and it is my practice to reject any document that is not signed and dated. This goes directly to data integrity: attributable, legible, contemporaneous, original and accurate. Using source documents without dates and signatures puts your submission at risk. If your company attempts to establish data integrity retroactively through a controlled DMS on documents prepared internally or by another party, that could have very serious legal implications including being construed as fraud. If your CMC team will not provide signed and dated documentation of their data and activities, I suggest you get executive management involved. 

Data integrity is one of the most frequent 483 and Warning Letter observations. The situation you are describing hits on 5 out of 8 bullet points for triggering data integrity violations leading to Warning Letters (https://integrao.com/data-integrity-fda-483s-and-warning-letter-trends/). I strongly urge you to hit the pause button on your Module 3 until such time as this is resolved in a compliant manner.

Best of luck,

Hello,

I am working on updating Module 3 sections for an IND as we are beginning Phase 3. This is a clinical-stage biotech and this is the DS and DP that will be used in registrational studies.
The documents I received from CMC for submission do not include version nor date. I would appreciate if others can comment if we should be including versioning and/or date. These documents are not in a controlled document management system. We receive Word documents from CMC and regulatory pdf's and publishes them. There is no formal approval/signature. 
Would it be sufficient to use a controlled DMS to capture formal review and approval? If so, would we still need to add version and/or date to the documents?
Thank you in advance for your advice.

Thank you for your response. Just to confirm - all of the source are ALCOA and CMC is amenable to versioning and dating. They also track document development and QC currently but using MS Word.

The intent with using DMS would be to draft the documents and import final drafts for review and approval into DMS (prior to submission). I do not feel the drafting all needs to be done in DMS - would you agree?

Good morning, Anonymous.

I do a lot of late-stage Module 3 writing, and it is my practice to reject any document that is not signed and dated. This goes directly to data integrity: attributable, legible, contemporaneous, original and accurate. Using source documents without dates and signatures puts your submission at risk. If your company attempts to establish data integrity retroactively through a controlled DMS on documents prepared internally or by another party, that could have very serious legal implications including being construed as fraud. If your CMC team will not provide signed and dated documentation of their data and activities, I suggest you get executive management involved. 

Data integrity is one of the most frequent 483 and Warning Letter observations. The situation you are describing hits on 5 out of 8 bullet points for triggering data integrity violations leading to Warning Letters (https://integrao.com/data-integrity-fda-483s-and-warning-letter-trends/). I strongly urge you to hit the pause button on your Module 3 until such time as this is resolved in a compliant manner.

Best of luck,

Hello,

I am working on updating Module 3 sections for an IND as we are beginning Phase 3. This is a clinical-stage biotech and this is the DS and DP that will be used in registrational studies.
The documents I received from CMC for submission do not include version nor date. I would appreciate if others can comment if we should be including versioning and/or date. These documents are not in a controlled document management system. We receive Word documents from CMC and regulatory pdf's and publishes them. There is no formal approval/signature. 
Would it be sufficient to use a controlled DMS to capture formal review and approval? If so, would we still need to add version and/or date to the documents?
Thank you in advance for your advice.

My understanding from your original message was that the DMS was to be used retroactively. My apologies if I was incorrect.

Drafts are seldom part of the DMS until they have been sent for review. Once they are sent for review they should be in the DMS so edits can be tracked through version control. It is my practice to use the version control feature of my own DMS in a folder not accessible to the client until such time as I feel a document is ready for client review. At that time I move it to a folder that is accessible to the client as the original version. 

I hope I am being helpful,

Thank you for your response. Just to confirm - all of the source are ALCOA and CMC is amenable to versioning and dating. They also track document development and QC currently but using MS Word.

The intent with using DMS would be to draft the documents and import final drafts for review and approval into DMS (prior to submission). I do not feel the drafting all needs to be done in DMS - would you agree?

Good morning, Anonymous.

I do a lot of late-stage Module 3 writing, and it is my practice to reject any document that is not signed and dated. This goes directly to data integrity: attributable, legible, contemporaneous, original and accurate. Using source documents without dates and signatures puts your submission at risk. If your company attempts to establish data integrity retroactively through a controlled DMS on documents prepared internally or by another party, that could have very serious legal implications including being construed as fraud. If your CMC team will not provide signed and dated documentation of their data and activities, I suggest you get executive management involved. 

Data integrity is one of the most frequent 483 and Warning Letter observations. The situation you are describing hits on 5 out of 8 bullet points for triggering data integrity violations leading to Warning Letters (https://integrao.com/data-integrity-fda-483s-and-warning-letter-trends/). I strongly urge you to hit the pause button on your Module 3 until such time as this is resolved in a compliant manner.

Best of luck,

Hello,

I am working on updating Module 3 sections for an IND as we are beginning Phase 3. This is a clinical-stage biotech and this is the DS and DP that will be used in registrational studies.
The documents I received from CMC for submission do not include version nor date. I would appreciate if others can comment if we should be including versioning and/or date. These documents are not in a controlled document management system. We receive Word documents from CMC and regulatory pdf's and publishes them. There is no formal approval/signature. 
Would it be sufficient to use a controlled DMS to capture formal review and approval? If so, would we still need to add version and/or date to the documents?
Thank you in advance for your advice.

Hello,

I am working on updating Module 3 sections for an IND as we are beginning Phase 3. This is a clinical-stage biotech and this is the DS and DP that will be used in registrational studies.
The documents I received from CMC for submission do not include version nor date. I would appreciate if others can comment if we should be including versioning and/or date. These documents are not in a controlled document management system. We receive Word documents from CMC and regulatory pdf's and publishes them. There is no formal approval/signature. 
Would it be sufficient to use a controlled DMS to capture formal review and approval? If so, would we still need to add version and/or date to the documents?
Thank you in advance for your advice.

Technically, i guess, the documents get versioned (from FDA's perspective)  as part of the sequence in which the documents are submitted.  However, for internal reasons, I typically include a month and year in the footer of the Word version of each document to provide a level of versioning.

Without an eDMS, I would ensure that each document is QCed by someone other than the author to ensure the data in the document are traceable should any questions arise, meaning traceable to a source document like a batch record, certificate of analysis, laboratory notebook, etc.  Then, after team review / revision, I would have the head of CMC sign an approval form for the whole CMC submission to make that person accountable for the information.  This will help ensure quality and accuracy of the information, plus accountability.  You can just create a simple approval form for the technical lead(s) and the head of CMC to sign on paper (or AdobeSign or DocuSign).  On the approval form, reference the month/year versioning in the documents to be approved.  I would have the approval done using the published PDFs rather than the Word documents since the PDFs are the "official version" since they are the documents being submitted to FDA.

You might also want to have a general regulatory submissions document review / approval SOP that has an approval form if you want to formalize the process, which can be used for all kinds of submission documents, not just CMC.

Hello,

I am working on updating Module 3 sections for an IND as we are beginning Phase 3. This is a clinical-stage biotech and this is the DS and DP that will be used in registrational studies.
The documents I received from CMC for submission do not include version nor date. I would appreciate if others can comment if we should be including versioning and/or date. These documents are not in a controlled document management system. We receive Word documents from CMC and regulatory pdf's and publishes them. There is no formal approval/signature. 
Would it be sufficient to use a controlled DMS to capture formal review and approval? If so, would we still need to add version and/or date to the documents?
Thank you in advance for your advice.

Hello,

I am working on updating Module 3 sections for an IND as we are beginning Phase 3. This is a clinical-stage biotech and this is the DS and DP that will be used in registrational studies.
The documents I received from CMC for submission do not include version nor date. I would appreciate if others can comment if we should be including versioning and/or date. These documents are not in a controlled document management system. We receive Word documents from CMC and regulatory pdf's and publishes them. There is no formal approval/signature. 
Would it be sufficient to use a controlled DMS to capture formal review and approval? If so, would we still need to add version and/or date to the documents?
Thank you in advance for your advice.

I'm not aware of there being a requirement to have a date/version on CTD documents, but I highly recommend adding at least a date to header or footer of each document.  To me just a date is suffice. I've worked at companies that include both a date and version/code and some that just use a date. I think you could be setting yourself up for some headaches if you don't include - even if a DMS can capture that info.

Hello,

I am working on updating Module 3 sections for an IND as we are beginning Phase 3. This is a clinical-stage biotech and this is the DS and DP that will be used in registrational studies.
The documents I received from CMC for submission do not include version nor date. I would appreciate if others can comment if we should be including versioning and/or date. These documents are not in a controlled document management system. We receive Word documents from CMC and regulatory pdf's and publishes them. There is no formal approval/signature. 
Would it be sufficient to use a controlled DMS to capture formal review and approval? If so, would we still need to add version and/or date to the documents?
Thank you in advance for your advice.