Creating Corporate Entities 

first step

There are three classes of Corporate Entities whose structural definition can be initiated/completed in the first step of the corporate entity hierarchy creation process:

  • Substance and its role in the Corporation - global/basic entity - initiated by decision or automatically and structurally completed

  • Reference Medicinal Product - global/basic entity - initiated by decision and structurally completed

  • Organization and its role in the Corporation - global/basic entity - initiated by decision or automatically and structurally completed

For the three classes of Corporate Entities the structural definition is initiated and completed in this step.

For the three classes of Corporate Entities the narrative definition is initiated by the automatic creation of an appropriate directory structure with replacement documents.

 The creation and structural definition of the global/basic Corporate Entities and their roles in the Pharmaceutical Corporation is the first step in the creation of corporate entities hierarchy, one of the cornerstones of the eCTD Integral Information System.

There are no prerequisites imposed by the eCTD Integral Information System for global/basic Corporate Entities creation.

The global/basic Corporate Entities, Substances, Reference Medicinal Products and Organizations, are mostly defined by external factors, for example:

  • Country and language codes - defined by global standards
  • Organizations - defined by Chambers of Commerce
  • Areas of expertise - defined by global quality standards
  • Substances - defined by science
  • International Nonprotected Names (INNs) of Substances
  • Anatomical Therapeutic Chemical codes - defined by WHO
  • Routes of administration - defined by Pharmacopoeias
  • Clinical Indications - defined by the Health Authorities
  • Quality of Marketed Substances - defined by Pharmacopoeias, Drug Master File...
  • Dosage form types - defined by Pharmacopoeias
  • Immediate packaging types - defined by Pharmacopoeias 
  • Manufacturing operations - defined by the Health Authorities
  • Marketing Authorization data of the Reference Medicinal Products
  • etc.

but their role in the Pharmaceutical Corporation must be defined within the Pharmaceutical Corporation  itself.

The creation of global/basic Corporate Entities begins with their structural definition on the appropriate entity creation application form based on one of the "basis for creation" document types generated by the top-level officials of the Pharmaceutical Corporation.

Their narrative definition can begin as soon as the "minimal data set" is inserted into the eCTD Integral Information System Database because at that instance an appropriate directory tree with replacement narrative documents is created. As their complete narrative definition is a prerequisite to being part of the initial submission to relevant Health Authorities and/or Business Partners, their narrative definition can be carried out up to that point.

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Substance and its role in the Corporation

initiated by decision or automatically and structurally completed

The creation of a Substance entity in the eCTD Integral Information System must be instigated with a "basis for creation"  type of document, sent via Enriched Email to the top-level cmc entity person as a:

  • Enriched email message with:
    • Topic - "New Substance"
    • Subtopic - "Introduction of a New Substance"
    • Subject - "Decision to introduce a new Substance"
    • Attachment - "Decision document"
      sent for the creation of an innovative active substance, excipient, starting material or impurity. Details and justification for such a business move together with necessary resources must be given in that document and should be signed by a corporate person with the appropriate authority
  • Enriched email automatic notification with:
    • Topic - "New Substance "
    • Subtopic - "Introduction of a New Substance"
    • Subject - "Decision to introduce a new Active Substance"

sent when first Reference Medicinal Product for a

new Generic Active Substance
or

Well-Known Medicinal Product
or

Medicinal Product with informed consent

is completely structurally defined.

The top-level cmc entity person can choose to initiate the definition process themselves or to forward the email to one of their subordinate colleagues taking into account the required professional skills and security classification of the meter in question.

Depending on the scenario, one of enriched emails is displayed on the sub-application form "Correspondence" of the “Corporate Entity creation/Substance/Structural Data” application form. To establish an entity creation chain of correspondence, this enriched email must be checked, and after returning to the main application form, the process of structural definition can begin.

Substance - structural definition

The structural definition of a Substance is done on the "Corporate Entity creation/Substance/Structural Data" application form .

General structural data

The Substance is defined by the following general structural data:

  • Name
  • Substance role in the corporation
    • active substance
    • active substance in fixed combination
    • excipient
    • starting material
    • intermediate
    • impurity
  • CMC entity person responsible
  • Substance type
  • Standard

For each Substance, substance type is assigned according to the classification specified in the:

"EMA Substance names best practice" EMA/40951/2014, Rev. 1

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. At the insert, the designated cmc entity person is informed of the new assignment through an automatically generated enriched email notification. Also, at the same time, the designated cmc entity person is set as a "designated follower" of all enriched email messages related to the newly introduced Substance. 

The "designated follower" is responsible for the complete structural definition and subsequent structural changes and is automatically granted the necessary system privileges with the ability to delegate the assigned rights to an Assistant or Agent using the features of the Enriched Email Client.

During the definition of the minimal set of structural data of a Substance, a unique editable "var" abbreviation "subst" is automatically generated, which is later used as part of template directory paths and document names. 

The record with the minimal set of structural data can not be used to define Corporate Entities of the higher level but can be chosen as a topic in the Enriched Email in order to collect other data required to completely structurally and narratively define Substance.

Active Substances

When the record is inserted and if the Substance has the role "active substance" or "excipient", a core sequence and directory tree with replacement entity definition narrative documents is generated. All subsequent actions of the structural and narrative definition of the Substance are related to that core sequence.

The role of the active substance indicates expectations that the Medicinal Product will be created and eventually authorized for distribution on the market. Therefore, additional structural data are defined for active substances:

  • Legal basis for future Marketing Authorization application (Directive 2001/83/EC)
    • Article 8(3) full application 
    • Article 10(1) generic application
    • Article 10(3) hybrid application
    • Article 10(4) similar biological application
    • Article 10a well-established use application
    • Article 10b fixed combination application
    • Article 10c informed consent application
    • Article 16a traditional use for herbal medicinal product application
  • Reference Medicinal Product for:
    • Generic Medicinal Products
    • Well-Known Medicinal Products
    • Medicinal Products with Informed Consent

The Reference Medical Product is introduced into the eCTD Integral Information System on a separate application form "Corporate Entity creation/Medicinal Product/Structural Data - Reference MP" for Active Substances with an International Nonproprietary Name (INN).

Fixed Combination of active substances

The Fixed Combination of active substances can be introduced into the eCTD Integral Information System on a separate "Corporate Entity creation/Substance/ Fixed Combination of active substances" application form . 

The Fixed Combination of active substances is later used as a separate entity for the definition of the Corporate Entities of the higher level.

 Completion of the structural definition process

When all structural data are completely defined the Substance is assigned a status "completely structurally defined" with ability to be used to define Corporate Entities of the higher level.

At that point, two entity creation correspondence tracks are initiated, Substance  track and Medicinal Product track:

  • Substance track is initiated if the Substance has one of the roles:

    • active substance

    • active substance in fixed combination

    • excipient

    • starting material

and an automatically generated enriched email notification is sent to the top-level cmc entity person, with the information that for the newly defined Substance a distributing Organization has to be introduced into the eCTD Integral Information System.

  •  Medicinal Product track is initiated if the substance is an active substance and one of the following automatically generated enriched email notifications is sent:
    • if the role is an active substance and the proposed legal basis for a future Marketing Authorization Application  in accordance with Article 8(3), an automatically generated enriched email notification is sent to the top-level pre-clinical entity person with the information that a Pre-Clinical Tests entity with the Marketed Substance of the newly defined Substance has to be created
    • if the role is an active substance and the proposed legal basis for a future Marketing Authorization Application - generic application (Article 10(1)) whose Reference Medicinal Product is administered directly into the bloodstream, an automatically generated enriched email notification is sent to the top-level cmc entity person with the information that a Generic Intravenous Medicinal Product entity has to be created using the newly defined Substance
    • if the role is an active substance and the proposed legal basis for a future Marketing Authorization Application - generic application (Article 10(1)) whose Reference Medicinal Product is not administered directly into the bloodstream, an automatically generated enriched email notification is sent to the top-level clinical entity person with the information that a bioequivalence Clinical Trial entity with the Generic Investigational Medicinal Product using the newly defined Substance has to be created 
    • if the role is an active substance and the proposed legal basis for a future Marketing Authorization Application - hybrid application (Article 10(3)), an automatically generated enriched email notification is sent to the top-level clinical entity person with the information that a Clinical Trial  with Generic Investigational Medicinal Product(s) has to be created using the newly defined Substance
    • if the role is an active substance and the proposed legal basis for a future Marketing Authorization Application - similar biological application (Article 10(4)), an automatically generated enriched email notification is sent to the top-level clinical entity person with the information that a Clinical Trial with Generic Investigational Medicinal Product(s) has to be created using the newly defined Substance
    • if the role is an active substance and the proposed legal basis for a future Marketing Authorization Application - well-established use application (Article 10a), an automatically generated enriched email notification is sent to the top-level cmc entity person with the information that a Generic Medicinal Product has to be created using the newly defined Substance
    • if the role is an active substance and the proposed legal basis for a future Marketing Authorization Application - informed consent application (Article 10c), an automatically generated enriched email notification is sent to the top-level cmc entity person with the information that a Medicinal Product entity has to be created using the newly defined Substance
    • if the role is an active substance and the proposed legal basis for a future Marketing Authorization Application - traditional use for herbal medicinal product application (Article 16a), an automatically generated enriched email notification is sent to the top-level clinical entity person with the information that the Clinical Trial with Generic Investigational Medicinal Product(s) has to be created using the newly defined Substance

The recipients of the above enriched email notifications decide whether to initiate the creation process themselves or to forward the message to another corporate entity person under their jurisdiction.

It is important to note that the structural characteristics of the Substance such as substance ID, name, protected name, INN, etc. are used to navigate the correspondence chains for the Substance track and Medicinal Product track, as well as during the automatic generation of initial submissions for Preclinical Tests, Clinical Trial and Marketing Authorization Application projects. They are also used to automatically fill in electronic Application Form (eAF).

A detailed description of a structural definition process is presented here.

Substance - narrative definition

If the minimal set of structural data for the Substance is met and the record is inserted into the eCTD Integral Information System Database, for the Substance with the role of "active substance" with a legal basis in accordance with Article 8(3) a directory structure with replacement entity definition documents marked with (*) is automatically created.

The designated cmc entity person is responsible for the creation and subsequent changes of narrative definition documents. 

New or changed documents are uploaded using the application form "Corporate Entity creation/Substance/Narrative Data".

When all replacement documents are replaced with newly created narrative documents, status of the new Substance entity  is set to “completely defined - draft”

At that point, the automatically generated enriched email notification is sent to the top-level cmc entity person with the information that the new Substance has been completely defined.

A detailed description of a narrative definition process is presented here

Reference Medicinal Product 

initiated by decision and structurally completed

The first step in the introduction and definition of a Generic Medicinal Product with one of the legal basis:

  • Article 10(1) generic application
  • Article 10(3) hybrid application
  • Article 10(4) similar biological application

is the introduction of a new or the selection of an existing Reference Medicinal Product that will serve as the basis for a Marketing Authorization Application.

The same approach is used for Medicinal Products with the following intended legal bases:

  • Article 10a well-established use application
  • Article 10b fixed combination application
  • Article 10c informed consent application
  • Article 16a traditional use for herbal medicinal product application

Therefore, the “Decision to introduce a new Reference Medicinal Product” contains definition of the Reference Medicinal Product and its intended use in the new Marketing Authorization Application.

The Decision to introduce a new Reference Medicinal Product or to use exiting one with different intentions, is sent to the top-level cmc entity person as:

  • Enriched email message with:
    • Topic type: Medicinal Product
    • Topic - "New/New use - Reference Medicinal Product"
    • Subtopic - "Introduction of a New Medicinal Product"
    • Subject - "Decision to introduce a new Reference Medicinal Product"
    • Attachment - "Decision to introduce a new Reference Medicinal Product"
      Details and justification for such a business move together with necessary resources must be given in that document and should be signed by a corporate person with the appropriate authority

The top-level cmc entity person can choose to initiate the definition process themselves or to forward the email to one of their subordinate colleagues taking into account the required professional skills and security classification of the meter in question.

This enriched email message is displayed on the sub-application form "Correspondence" on the “Corporate Entity creation/Medicinal Product/Structural Data - Reference MP” application form. To establish an entity creation chain of correspondence, this enriched  email must be checked, and after returning to the main application form, the process of structural definition can begin.

Reference Medicinal Product - structural definition

The structural definition of a Reference Medicinal Product is done on the application form "Corporate Entity creation/Medicinal Product/Structural Data - Reference MP".

Reference Medicinal Product is defined by the following general structural data:

  • International Non-Proprietary Name or surrogate INN name
  • Dosage form
  • Active substance(s)
  • Strength
  • Route of administration
  • Therapeutic Indications

and additionally and optionally  by the Reference Medicinal Product marketing authorization data:

  • Country where Reference Medicinal Product is authorized
  • Product (invented) name
  • Marketing Authorization Holder
  • Marketing Authorization number
  • Procedure number for MRP/DCP/National (if applicable)
  • Date of authorization

When all structural data are completely defined, the Reference Medicinal Product is assigned the status "completely structurally defined" with the ability to be used to define Corporate Entities of the higher level:

  • new corresponding Active Substance
    or, if a corresponding Active Substance already exist in the eCTD Integral Information System,
  • new Medicinal Product
     or
  • new Clinical Trial(s) with the Generic Investigational Medicinal Product(s)

At that point, one of the automatically generated enriched email notifications is sent to the top-level cmc entity person:

  • if the corresponding Active Substance does not exist in the eCTD Integral Information System
    an automatically generated enriched     email notification is sent  to the top-level cmc entity person with the information that a new corresponding Active Substance has to be created for a newly defined Reference Medicinal Product
  • if one or more corresponding Generic Active Substances already exist in the eCTD Integral Information System and:
    • the newly defined Reference Medicinal Product is administered directly into the bloodstream
    • the proposed legal basis is generic application (Article 10(1))

an automatically generated enriched email notification is sent to the top-level cmc entity person with the information that a Generic Intravenous Medicinal Product has to be created using a newly defined Reference Medicinal Product 

  • if one or more corresponding Generic Active Substances already exist in the eCTD Integral Information System and:
    • the newly defined Reference Medicinal Product is not administered directly into the bloodstream
    • the proposed legal basis is generic application (Article 10(1))

an automatically generated enriched email notification is sent to the top-level clinical entity person with the information that a bioequivalence Clinical Trial has to be created using a newly defined Reference Medicinal Product as a basis for the Generic Investigational Medicinal Product.

  • if one or more corresponding Generic Active Substances already exist in the eCTD Integral Information System
    • the newly defined Reference Medicinal Product is not administered directly into the bloodstream
    • the proposed legal basis is  hybrid application (Article 10(3))

an automatically generated enriched email notification is sent to the top-level clinical entity person with the information that Clinical Trials have to be created using a newly defined Reference Medicinal Product as the basis for the Generic Investigational Medicinal Product(s)

  • if one or more corresponding Generic Active Substances already exist in the eCTD Integral Information System
    • the proposed legal basis is well-established use application (Article 10a)

an automatically generated enriched email notification is sent to the top-level cmc entity person with the information that a Generic Medicinal Product has to be created using a newly defined Reference Medicinal Product

  • if one or more corresponding Active Substances already exist in the eCTD Integral Information System
    • the proposed legal basis is informed consent application (Article 10c)

    • an automatically generated enriched email notification is sent to the top-level cmc entity person with the information that a Innovative Medicinal Product has to be created using a newly defined Reference Medicinal Product 

    It is important to note that the structural characteristics of the Reference Medicinal Product such as INN, dosage form and strength, MAH data and legal basis are used to navigate the correspondence chains for the Medicinal Product track, as well as during the automatic generation of initial submissions for Clinical Trial and Marketing Authorization Application projects. They are also used to automatically fill in electronic Application Form (eAF).

    A detailed description of a structural definition process is presented here.

    There is no need to narratively define a Reference Medicinal Product.

    Organization and its role in the Corporation

    initiated by decision or automatically and structurally completed

    The creation of an Organization in the eCTD Integral Information System is done in order to establish a new corporate company or to establish a business relationship with an existing company.

    The creation of an Organization entity in the eCTD Integral Information System must be instigated with one of the "basis for creation" type of documents sent to the top-level cmc entity person via Enriched Email as a:

    • Enriched email automatic notification with:
      • Topic - "New Organization"
      • Subtopic - "Introduction of a New Organization"
      • Subject - "The notification to introduce a new Distributor for a Marketed  Substance"
        sent when corresponding Substance is completely structurally defined
      • Initiator - enriched email that was used as a basis for creation of the Substance
    • Enriched email notification with:
      • Topic - "New Organization
      • Subtopic - "Introduction of a New Organization"
      • Subject - " The notification to introduce a new contact/Organization
        sent from the Enriched Email Client to create a new contact and associated Organization
    • Enriched email message with:
      • Topic - "New Organization"
      • Subtopic - "Introduction of a New Organization"
      • Subject - "The decision to establish a new corporate Organization or to engage in the business relationship with an existing Organization"
      • Attachment - "Decision document"
        Details and justification for such a business move together with projected necessary resources must be given in this document and should be signed by a corporate person with the appropriate authority
    • Enriched email automatic notification with:
      • Topic - "New Organization"
      • Subtopic - "Introduction of a New Organization"
      • Subject - "The notification to define new manufacturer for <Name of the Marketed Substance-Production Chain> "
      • Initiator - enriched email that was used as a basis for creation of the Marketed Substance

    The top-level cmc entity person can choose to initiate the definition process themselves or to forward the email to one of their subordinate colleagues taking into account the required professional skills and security classification of the meter in question.

    Depending on the scenario, one of enriched emails is displayed on the sub-application form "Correspondence" on the “Corporate Entity creation/Organization/Structural Data” application form. To establish an entity creation chain of correspondence, this enriched email must be checked, and after returning to the main application form, the process of structural definition can begin.

    Organization - structural definition

    The definition of an Organization must start  with the companies that belong to the Pharmaceutical Corporation and must start from the top, the mother/parent company, and than continue gradually level by level, down. After that, companies not belonging to the Pharmaceutical Corporation  can be defined  in conjunction with their relationship with the Pharmaceutical Corporation companies.

    The same applies to the hierarchy of persons in various areas of expertise. First, the top level supervisor must be defined, and then the whole reporting persons hierarchy.

    A minimal set of structural data is specified with the (*) on the application form "Corporate Entity creation/Organization/Structural Data" and they are a prerequisite for the insertion of the record into the eCTD Integral Information System Database. Record with a minimal set of structural data can not be used to define entities of the higher level but can be chosen as a topic in the Enriched Email correspondence in order to collect other data required to completely structurally and narratively define Organization.

    When the record is inserted, a core sequence is generated and all subsequent structural and narrative actions of the Organization definition are related to that sequence. The designated cmc entity person is informed of the new assignment through an automatically generated enriched email notification. Also, at the same time, the designated cmc entity person is set as a "designated follower" of all enriched email messages/notifications related to the newly introduced Organization. The "designated follower" is responsible for the complete structural definition and subsequent structural changes and is automatically granted the necessary system privileges with the ability to delegate the assigned rights to an Assistant or Agent using the features of the Enriched Email Client.

    During the definition of the minimal set of structural data of the Organization, an editable unique "var" abbreviation "org", xx characters long, is automatically generated which is later used as a part of template directory paths and file names. 

    Structural data relevant for the definition of an Organization can be divided into five categories and their definition must be done in accordance with the following sequence:

    • General information
    • Type of organizational unit
    • Legal position within the Corporation or business relationship with the Corporation
    • Areas of expertise of the Organization
    • Main contact persons for each area of expertise

    When all structural data are completely defined the Organization is assigned a status "completely structurally defined" and can be used to define Corporate Entities of the higher level.

    At that point, if the Organization has a GDP certificate for distribution of substances, enriched email automatic notifications, one for each substance in the substance distribution list, are sent to the cmc entity person(s) designated for the definition of the distributing Organization(s). Each message contains information that a Marketed Substance entity has to be created for each of the Substances in the Organization's substance distribution list.

    For legal entities belonging to the Pharmaceutical Corporation, a Functional Organizational Structure is also defined.

    It is important to note that the structural characteristics of the Organization such as organization ID, name, addressees, GxP certificate, GDP substance distribution list, etc. are used to navigate the correspondence chains for the Substance track, as well as during the automatic generation of initial submissions for Preclinical Tests, Clinical Trial and Marketing Authorization Application projects. They are also used to automatically fill in electronic Application Form (eAF).

    A detailed description of a structural definition process is presented here. 

    Organization - narrative definition

    If the minimal set of structural data for the Organization is met and the record is inserted into the eCTD Integral Information System Database, a directory structure with replacement entity definition documents marked with (*) is automatically created.

    The designated cmc entity person is responsible for the creation and upload of narrative documents. This person is also responsible for their subsequent changes. New or changed documents are uploaded using the application form "Corporate Entity creation/Organization/ Narrative Data".

    When all replacement documents are replaced with newly created narrative documents, status of the new Organization entity  is set to “completely defined - draft”

    At that point, the automatically generated enriched email notification is sent to the top-level cmc entity person with the information that the new Organization has been completely defined.

    A detailed description of a narrative definition process is presented here