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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.
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In the following, we incrementally explain why we need roles, and how contextualized roles are modeled in general and instantiated with examples.
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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)
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Diagram 2: Example for the universal statement "Amlodipine mesylate monohydrate is included in Amlodipine EMC"
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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 Mesylate Monohydrate plays the role of active ingredient in Amlodipine EMC
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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).
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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 below The diagrams 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 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).
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Diagram 7: Modeling N-hydroxymethyl aripiprazole as the active moiety for Aripiprazole lauroxil in a an FDA patent exclusivity context
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