Active substance registration

Good afternoon! Can anybody advise how to complete the form for registering an active substance, in the case of an ATMP? In most cases, there will be no chemical name or CAS number, and the company may not yet have a proposed INN. What is the minimum amount of information needed for the form to be successfully accepted?

Please note that the following substance information should be provided for cell therapies:

• Source (i.e. Autologous, Allogeneic or Xenogeneic);
• Tissue of origin (if applicable, e.g. bone-marrow derived, adipose-derived);
• Target cell type (e.g. mesenchymal stem cells, fibroblasts, chondrocytes);
• Any relevant modifications (e.g. genetically modified, ex vivo expanded).

In addition, the substance company code should also be provided.

Dear Dr. Batista,

Thank you for your reply. Should this extra information be entered as additional rows in Sheet 1 of the Substance Request Form, or provided to the EMA Service Desk as a separate document?

We are also unsure how to complete Sheet 2 of the Excel form, entitled 'nature of the active substance (levels 2 and 3)'. This is not fully explained in section 7.2 of the IRIS Guide to Registration (EMA/31242/2019). Is the applicant supposed to put check marks in column B perhaps?

And in the case of an ATMP, are the categories in Sheet 2 intended to match the ATMP classification? Thus for example, a cell therapy with genetic modification (such as a CAR-T) would be classified as 'gene therapy', whereas one without genetic modification would be 'cell therapy'. Any guidance would be appreciated.

Thank you!

You can provide the requested information concatenated into one line. For example: "Allogeneic bone marrow derived mesenchymal stromal cells, ex-vivo expanded". 

Regarding the sheet 2, please disregard "nature of the active substance" in the Substance Request Form. That information will be filled directly in IRIS, when you are creating your RPI. That list is supposed to match the ATMP classification.

Good afternoon everybody,
I have additional questions on the registration of an active substance:
1. Does the applicant need to fill only the lines of the "Name type" that are pertaining to the medicinal product in Sheet 1 of the Substance Request Form?
2. In case of a cell-derived product (biological medicinal product), does the same information than ATMP need to be provided?
3. Can the request be sent by an external consultant, acting on behalf of the applicant and registered as IRIS Manager for the applicant?
Thank you in advance.

Kind regards,
Lucia

1. Only sheet 1 needs to be filled with all substance names available

2. For an ATMP, the following information should be provided:

• Source (i.e. Autologous, Allogeneic or Xenogeneic);
• Tissue of origin (if applicable, e.g. bone-marrow derived, adipose-derived);
• Target cell type (e.g. mesenchymal stem cells, fibroblasts, chondrocytes);
• Any relevant modifications (e.g. genetically modified, ex vivo expanded).

3. The request can be submitted by any user in EMA Service Desk. No special role is required.

I have couple of questions to the Privacy settings in the Substance request form.

The privacy setting in the form is set to "public" by default. I understand that if the substance is part of the investigational medicinal product currently under development, the Privacy setting could be adjusted accordingly i.e. "public" vs "restricted".

1. is there a minimum of fields that must be set to "public"?
2. where i.e. in which databases will the data be restricted from publishing?
3. can the privacy setting be changed post registration of the active substance?

Please find below the reply to your questions:

1. The substance preferred term must always be public. For substances that arent in the public domain, this name can be a company code. However, note that a company code will not be sufficient to support certain procedures at EMA (e.g. Orphan Designation, Paediatric Investigation Plan/Waiver, Marketing authorization, etc.) when the substance is part of an RPI. 
2. If a substance name is registered as a restricted synonym,  it will not be visible in any EMA public database (e.g. XEVMPD, EUTCT, IRIS, eAF, etc.).
3. Privacy settings can be adjusted after registration by submitting a change request from the requestor or by EMA if the substance name becomes available in the public domain (e.g. INN is issued by WHO or the product gets marketing authorisation). EMA may also change privacy settings, for examples when rINNs are published by WHO. 

Registration of CAR Tell product in IRIS,
Dear all,
If I want to use an individualised ATMP (without approval in the EU), a CAR T Cell product, in a clinical trial, do I have to register the product individually for each patient or is the CAR considered an active substance?
Thank you for your answer in advance
Kind Regards
Rita