Introduction

Ontologies are a representation of domain knowledge using defined concepts and the relationships between those concepts in a manner understandable to both humans and machines.

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To capture the context, an established pattern in ontology modelling modeling is to use "roles". E, e.g., a human Max can play the role of "patient" in the context of a treatment. Or a substance can play the role of "active ingredient" in the context of one pharmaceutical product while the same substance may play the role of "excipient" in the context of a different product.

The role concept (hereafter referred to as 'role') and corresponding ontological role model pattern provide a structured and modular way to capture many different real-world complexities.

Related Competency Questions

• What is the active moiety of <SUBSTANCE>?
• What is the investigational/authorized medicinal product in <CLINICAL TRIAL>?

Relation to ISO-IDMP Standards

There is no general role pattern described in the ISO IDMP standards. However, roles are mentioned, e.g., for describing an ingredient in the context of a pharmaceutical product. See also Pattern: Ingredient Representing Ingredients - DRAFTAPPROVED

Modeling Pattern

In the following, we incrementally explain why we need roles, and how contextualized roles are modeled in general and instantiated with examples.

Universal Statement

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without Role

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Pattern

Diagram 1: Simple statement that is universally true and doesn't require context.

Example: Amlodipine Mesylate Monohydrate is included in Amlodipine EMC (a pharmaceutical product)

Diagram 2: Example for the universal statement "Amlodipine mesylate monohydrate is included in Amlodipine EMC"

Basic Role Pattern

In order to further specify a relationship, we use the basic role pattern that allows us to provide details that are valid only in a certain context in which the role about the role and about where the role is realized, appears, or occurs (through property "is manifested in".)

Diagram 3: The relationships between the object that plays the role and the context in which it is manifested are pairs of inverse relationships respecitively.Of course basic role pattern

The relationships "plays role" and "is played by" as well as the relationships "is manifested in" and "manifests" are inverse relationships, respectively. Of course, these general classes "Thing" and "Role" are instantiated with more specific subclasses, as illustrated in the next example:

Example: Amlodpine

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Mesylate Monohydrate plays the role of active ingredient in

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Amlodipine EMC

Diagram 4: Example for the basic role pattern: ingredient in a product

The important thing is that we can now attach all information that further specifies the role of Amlodipine mesylate monohydrate in the context of Amlodipine EMC to the middle role node in the graph, e..g., the strength or further context specification (see below). 

If multiple roles needs need to be further grouped or if a role doesn't uniquely connect an object with a contextits manifestation, then the Pattern: Constituencies - DRAFT /wiki/spaces/IDMP/pages/7247508 needs to be applied.

Role Hierarchy in IDMP-O

The role (https://www.omg.org/spec/Commons/PartiesAndSituations/Role) is modeled as a class and can be specialized with sub-classes, some of which are shown in diagram 2.the next figure

Diagram 2: The role class and its specialized sub-classes.

Everything below requires review/update

5: Role hierarchy

Optional Context Definition

The context is a "situation" or frame of reference in which something applies, exists, happens, or is used, and that helps to illustrate or explain it. As with roles, contexts can be further specified with sub-classes as shown in Diagram 3.

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Diagram 3: Context and its sub-classes.

Examples

Modeling the active moiety role for Amlodipine bezylate in the regulatory context

Amlodipine bezylate is used here as a simple example to demonstrate the modeling pattern for contextualized roles, where Amlodipine plays the active moiety role for the drug Amlodipine bezylate in a regulatory context. 

Diagram 4: Modeling Amlodipine as the active moiety for Amlodipine bezylate in a regulatory context6: Contextualization of Roles

As for roles, "context" can have subclasses to further specify its nature, e.g., jurisdiction, regulatory, scientific or similar.

Examples

Modeling the different active moiety roles for Aripiprazole

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Lauroxil in different contexts

The contextualized role pattern is used here to model interpretations of the active moiety role for Aripiprazole in different situations. Aristada is a drug developed by Alkermes and is composed of Aripiprazole lauroxil. Aripiprazole lauroxil is first metabolized to N-hydroxymethyl aripiprazole, which is then further metabolized to Aripiprazole which exerts pharmaceutical effects in on the body. From a regulatory perspective, Aripiprazole is thus the active moiety. However, based on the interpretation of a patent by the US court, based on the fillings by the owner of the intellectual property (IP) on Aripiprazole lauroxil, the active component is stated as the N-hydroxymethylated product instead. Diagrams 5 and 6 below The diagrams below demonstrate how in different contexts, the active moiety for Aripiprazole lauroxil can be either N-hydroxymethyl aripripazole or Aripiprazole itself.

NOTE: The differences in interpretation of active moiety for Aripiprazole lauroxil came about, as Otsuka Pharmaceuticals challenged the FDA's approval for a new drug application for Alkermes's drug Aristada (Aripiprazole lauroxil) stating that it ultimately metabolizes to Aripiprazole which is the active moiety for Otsuka Pharmaceutical's drug Abilify (Aripiprazole). However, under USP's salt policy, the active moiety for Aripiprazole lauroxil is designated as N-hydroxymethyl aripiprazole.

In the third example, the USP salt policy context is considered when naming the active moiety for Aripiprazole lauroxil. The USP (United States Pharmacopeia) Salt Policy outlines a naming and labeling approach for drug products containing an active ingredient that is a salt , and applies to drug product monograph titles published after the 1st of May 2013. According to the USP salt policy, Aripiprazole lauroxil is designated as the active moiety for Aripiprazole lauroxil (Diagram 7).

Active Moiety Role

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for FDA Exclusivity

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Drawio
border true diagramName Moiety Role - Aripiprazole - FDA Patent Exclusivity - simplified simpleViewer false links auto tbstyle top diagramDisplayName N-hydroxymethyl aripiprazole as the active moiety for Aripiprazole lauroxil in a FDA patent exclusivity regulatory context lbox true diagramWidth 883 revision 35

Diagram 57: Modeling N-hydroxymethyl aripiprazole as the active moiety for Aripiprazole lauroxil in a an FDA patent exclusivity context

Active Moiety Role

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FDA GSRS

Diagram 68: Modeling Aripiprazole as the active moiety for Aripiprazole lauroxil in a regulatory FDA GSRS context

Active Moiety Role

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: USP Salt Policy

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Drawio
border true diagramName Copy of Moiety Role - Aripiprazole - FDA GSRS context simpleViewer false links auto tbstyle top diagramDisplayName Aripiprazole lauroxil as the active moiety for Aripiprazole lauroxil in a USP salt policy context lbox true diagramWidth 791 revision 23

Diagram 79: Modeling Aripiprazole lauroxil as the active moiety for Aripiprazole lauroxil in a USP salt policy context

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name Example Aripiprazole.docx height 250

USP documentation

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