Substance - creation

  • Gathering of the documentation/data
  • Structural definition
  • Narrative definition

The creation of a new Substance begins with a "basis for creation" regular/enriched email message/notification with the topic "New Substance":

  • enriched email notification for the generic active substances after the creation of the corresponding Reference Medicinal Product
  • regular/enriched email message for the:
    • novel active substances 
    • excipients
    • starting material for substance manufacturing
    • impurities

with an attachment classified as "Decision to introduce a new Substance"

    Other entity definition documents that may be necessary for structural and narrative definition of the Substance are:

    • Active substance evidence and justification
      annex-23-subst

    Gathering of the documentation/data

    Gathering of documentation and necessary data for the structural and narrative definition of a new Substance can be done in advance, before the beginning of structural definition and subsequently when the Substance has become a topic in the enriched email correspondence.

    Before the beginning of the structural definition

    Gathering documentation related to the creation of a new Substance is a process that can begin before the receipt of the "basis for creation"  enriched email and subsequent beginning of the structural definition. During that period database record for the new Substance and directory tree of replacement narrative files does not exists in the eCTD Integral Information System and the only topic that can be used in the correspondence is "New Substance". Attached documents are classified and uploaded to the Corporate Documentation Cloud but they are not linked with the Substance that is being created. Nevertheless, linking all correspondence to the newly created Substance is essential and it can be done when the structural definition is started.

    After the beginning of the structural definition

    The cmc entity person begins the process of  Substance structural definition right after receiving the first "basis for creation" enriched email. When selecting a "basis for creation" enriched email on the "Correspondence" sub-application form, all related correspondence previously received relating to the Substance being created should also be selected.

    During the insertion of the record into the eCTD Integral Information System a core sequence and a directory tree of replacement narrative files are generated and the newly defined Substance automatically becomes the topic of the "basis for creation" enriched email and all selected previously received enriched emails. That can be seen when inserting additional data on the "correspondence" sub-application form.

    Previously received attachments/documents have to be manually assigned to the corresponding replacement files using the application form "Corporate Entity creation / Substance / Narrative data". The process is explained in the narrative definition section.

    All correspondence from then on should be conducted using enriched email messages and the newly-introduced Substance as the topic.

    During the subsequent correspondence and classification of the attachment(s), attached document(s) are automatically uploaded to the Corporate Documentation Cloud and assigned to the appropriate replacement files.

    Structural definition

    In order to create and structurally define a Substance following business processes must be performed in the presented order:

    1. Generation/receipt of a "basis for creation" regular/enriched email
    2. Selection of one "basis for creation" enriched email message/notification and related correspondence on the sub-application form "Correspondence" of the application form "Corporate Entity creation / Substance / Structural Data"
    3. Definition of general structural data of the Substance
    4. Optional definition of specific structural data related to the active Substance
    5. Completion of the structural definition
      1. Complete structural definition during the first session
      2. Complete structural definition in several sessions

    1. Generation/receipt of a "basis for creation" regular/enriched email

    The regular/enriched email message with the attachment "Decision to introduce a new Substance" sent by a corporate person with the appropriate authority to the high-level cmc entity person. The regular email message must be registered by the recipient.

    The enriched email notification automatically sent to the high-level cmc entity person after the creation of the corresponding Reference Medicinal Product.

    If necessary, additional correspondence using the same topic and subtopic can be made in order to clarify certain details. When all details are clarified, the structural definition process can be started by choosing the menu item "Corporate Entity creation / Substance / Structural Data" on the "Corporate Entities" application module.

    2. Selection of one "basis for creation" enriched email message/notification

    To create a new Substance, first, using the "Correspondence" sub-application form, a received "basis for creation" enriched email relevant to the new Substance being created must be selected from the non-processed correspondence documents. In addition, all enriched email messages classified as "related correspondence" pertaining to the same new Substance should also be selected in order to properly establish entity creation correspondence environment.

    3. Definition of general structural data of the Substance

    A minimal set of structural data is specified with the (*) and they are a prerequisite for the insertion of the record in the eCTD Integral Information System Database.

    For compendial substances, International Nonprotected Name  and intended legal basis are transferred from the Reference Medicinal Product.

    Using free text fields, internally used Substance name and various physicochemical properties of the Substance can be defined.

    Links to "MOLBASE" and "Chemical Book" can be provided using buttons on the application form. 

    Using the selection blocks, Substance's origin, corporate role, and type of standard must be specified.

      Using the LoVs, the security classification and cmc entity person responsible for the structural and narrative definition must be designated.

      4. Optional definition of specific structural data related to the active Substance 

      For active Substances additional data must be defined.

      First, the intended main indication for the first marketing authorization is defined using  the LoV of indications.

      Then, the mode of action is defined by selecting one from the LoV of predefined modes of action.

      When the minimal structural data set criterion is met and the Substance is introduced into the eCTD Integral Information System, a core sequence, directory tree of replacement narrative files, and a enriched email notification to the designated cmc entity person are generated.

      During subsequent correspondence and classification of attachment, the attached document(s) are automatically uploaded to the Corporate Documentation Cloud and assigned to the appropriate replacement narrative files.

      5. Completion of the structural definition

      The structural definition process can be completed in two ways:

      1. In one session when all structural data are defined
      2. in several sessions where
        1. in the first session only minimal data set and maybe some of the additional data are defined
        2. in the  next session(s) remaining additional data are defined

      Upon completion of the structural definition process, the Substance is assigned the status "completely structurally defined". 

      At the same time, Substance track and Medicinal Product track are initiated by:

      • enriched email notification to the top-level cmc entity person for a new Substance Distribution Organization 
        (initiating Substance track)
      • for generic active substances, depending on the situation, enriched email notification for:
        • new generic Medicinal Product - to the top-level cmc entity person or
        • new Clinical Trial - to the top-level clinical entity person 
          (initiating Medicinal Product track)
      • for novel active substances, enriched email notification for new Pre-Clinical Tests - to the top level pre-clinical person (initiating Medicinal Product track)

      5.1 Complete structural definition during the first session

      The minimal data set denoted with (*) is a prerequisite for the insertion of the record into the eCTD Integral Information System.

      If the minimal data set requirement is met, then confirmation of the complete structural definition is also prompted: "Is the structural definition of the entity complete?". If the complete structural definition is confirmed the record is inserted into the database of the eCTD Integral Information System with the status "completely structurally defined" with the ability to be used to define corporate entities of the higher level.

      5.2 Complete structural definition in several sessions

      In the first session only the minimal data set and maybe some additional data are defined. At the end of the session, confirmation of the complete structural definition is prompted. If the answer is negative, the record is inserted and the status of the entity is set to "incompletely defined".

      Additional structural data can be added on the same application form by clicking on the "Additional data" button and selecting the required Substance from the LoV of incompletely structurally defined Substances. Previous enriched emails related to the selected Substance can be seen on the "correspondence" sub-application form.

      The structural definition is completed when a positive response is given to the prompt for a complete structural definition.

      The Substance is assigned the status "completely structurally defined" with the ability to be used to define corporate entities of the higher level.

      Narrative definition

      The designated cmc entity person is responsible for complete narrative definition of the Substance.

      The eCTD documents can be either:

      • created by the designated cmc entity person and manually uploaded to the Corporate Documentation Cloud or
      • collected from related Business Partners via email correspondence and automatically uploaded to the Corporate Documentation Cloud during the enriched email processing of the Business Partner's regular email messages. 

      Therefore, in order to narratively define a Substance following business processes must be performed:

      1. Creation of eCTD documents and manual uploading to the Corporate Documentation Cloud
        and/or
      2. Collection of eCTD documents via email correspondence and automatic uploading to the Corporate Documentation Cloud
      3. Completion of the process

      1. Creation of eCTD documents and manual uploading to the Corporate Documentation Cloud

      Using any regular text processor eCTD documents have to be created and pdf files generated for uploading to the Corporate Documentation Cloud. If required, a verification process by a senior manager can be included upon request.  

      The process is initiated by choosing the menu item "Corporate Entity creation / Substance / Narrative Data" on the "Corporate Entities" application module.

      At the beginning, the LoV of incompletely narratively defined Substances is displayed.

      By double clicking on the required Substance, the directory tree with the replacement files is displayed.

      By double clicking on the file to be replaced the template file path is displayed in the box "Directory tree/replacement file path" and directory tree window with replacement files can be closed.

      Double clicking on the "Files from local disk" field opens a "File selection" window on the local workstation.

      By double clicking on the file to be uploaded, the file is selected and the "File selection" window is closed.

      By clicking on the "Upload eCTD file" button, the file is uploaded to the Corporate Documentation Cloud.

      By clicking the "eCTD file review" button, the file can be open for review.

      For each file complete history journal is shown with all relevant data: revision No, uploading date, registered email ID, core sequence ID, and cloud ID.

      2. Collection of eCTD documents via email and automatic uploading to the Corporate Documentation Cloud

      In case the eCTD documents were originally generated by the Business Partner, they can be obtained via email correspondence. During the processing of such a Business Partner's regular email message by the Enriched Email Client and using the email attachments classification, they are automatically uploaded to the Corporate Documentation Cloud.

      A regular email message with the eCTD document as an attachment.

      By selecting the Corporate Entity as a Theme and with proper selection of the Topic Class, Topic, and Sub-topic, the appropriate LoV of attachment types is displayed.

      By selecting the appropriate attachment type, during the registration processing, the attachment is uploaded to the corresponding narrative replacement file in the directory tree of replacement narrative files.

      If the same document is sent back and forth several times as an attachment, revisions are automatically generated.

      For example, if a contract is first sent as a draft, then signed by the first business partner, and then returned signed by the second partner, three revisions of the document will be automatically generated.

      In case eCTD documents are sent as an attachment in zip format, they must be classified as related documentation and then downloaded, unzipped and manually uploaded using the "Corporate Entity creation /Marketed/ Substance / Narrative Data" application form.

      3. Completion of the process

      When all the presented replacement files in the directory tree are replaced with written eCTD files, the process ends automatically and the Substance is set to be "completely structurally and narratively defined".