...

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

Universal Statement

...

without Role

...

Pattern

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

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

Diagram 2: Example for 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 about the role and about where the role is realized, appears, or occurs (through property "is manifested in")

Diagram 3: The 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:

...

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 Amlodipine EMC to the middle role node in the graph, e..g., the strength or further context specification (see below). 

...

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

The role class and its specialized sub-classes.

Diagram 5: Role hierarchy

Optional Context Definition

...

Diagram 6: Contextualization of Roles

As for roles, "context" can have subclasses to further specify its nature. 

Image Removed

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 context

, e.g., jurisdiction, regulatory, scientific or similar.

Examples

Modeling the different active moiety roles for Aripiprazole

...

Lauroxil in different contexts

Needs update see IDMP-514 : "Active Moiety for FDA Exclusivity" . TBD: Can we model this better as a role subclass?

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 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 demonstrate how in different contexts, the active moiety for Aripiprazole lauroxil can be either N-hydroxymethyl aripripazole Aripripazole or Aripiprazole itself.

NOTE: The differences in interpretation of active moiety for Aripiprazole lauroxil came about, as Otsuka Pharmaceuticals challenged 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

...

for FDA Exclusivity

Diagram 5: Modeling N-hydroxymethyl aripiprazole as the active moiety for Aripiprazole lauroxil in a FDA patent exclusivity context

Active Moiety Role

...

FDA GSRS

Diagram 6: Modeling Aripiprazole as the active moiety for Aripiprazole lauroxil in a regulatory FDA GSRS context

Active Moiety Role

...

: USP Salt Policy

...

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 2

Diagram 7: Modeling Aripiprazole lauroxil as the active moiety for Aripiprazole lauroxil in a USP salt policy context

...