Introduction

The topic of ingredients and the various roles an ingredient may play is a critical pattern in the IDMP ontology. The concept of something that is an ingredient is only meaningful in the context of the thing that it is an ingredient of (i.e., as a part of a product, product specification/recipe, story, etc.). The concept of ingredient is dependent on (1) a mapping to the thing that fills the role of being that ingredient (e.g., a pure substance), (2) the strength of that substance in the context of the "thing that it is an ingredient of", (3) an amount or percentage representing how much of that ingredient is required (which might be optional depending on whether the ingredient is referenced as part of a specific recipe or another context), and (4) a mapping to the thing that it is an ingredient of (the product, recipe, or something else). In other words, the concept, of ingredient, is not independent — it depends on other things, and would not exist outside of the context of a pharmaceutical product, manufactured item, recipe, or some other composite thing that has ingredients. 

How much of a substance is consumed via its use in a product or item is a property of the relationship between the substance, its role as an ingredient, and the thing that consumes it per the IDMP 11238 and 11615 standards. The dependency is modeled in the ontology in two ways — one that relates the substance to the product of which it is a part (i.e., the product composition), and secondly, as a reified relationship, called ingredient (which is a role in description logic / OWL modeling terms), with an inheritance hierarchy refining the various roles in the product composition, that the ingredient has. 

Related Competency Questions

• UC-1, CQ 3-1: What is the basis of strength for <substance x> in <product y>?
• UC-1, CQ 6: Which investigational/authorized medicinal products contain the substance <$Substance> or its active moiety?
• UC-1, CQ 7: Which manufactured items contain substance <x> as an ingredient of type “active”?

Relation to ISO Standards

The figure included below is taken from the ISO 11615 standard:

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1. Question: Can multiple substances be used to fill the same ingredient role in a given product, i.e., are they substitutable (the diagram says no — there can only be zero or one substance filling the ingredient role)? Can two distinct substances, foo and bar, interchangeably play the same role of active ingredient in a product that is made by a specific manufacturer under a specific marketing authorization (ignoring cases that have multiple active ingredients)? It is likely that two distinct substances could play a different role interchangeably, such as some excipient role, although perhaps not in the case of an active ingredient. The current model allows this, i.e., hasActiveIngredient is not functional at present. Answer: Currently no. If you change the substance it is a different product, even if it has the same pharmacological effect. This reinforces the notion that ingredient is a dependency.
2. Question: Can the same substance in the same or different amounts play two different roles in the same product, for example, the same chemical substance with the same molecular structure be an active ingredient and an excipient in the same pharmaceutical product? Answer: No 

Modeling Pattern

The resulting partial, high-level model using a knowledge graph modeling approach corresponding to Figure 12, above, with some details elided, is as follows:

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The roles identified above extend the ingredient class, with the codes expressed as a controlled vocabulary with code elements mapped to them. Figure 2, below, shows how the codes map to some of the roles, and how the model for ingredient corresponds to Figure 12 from the IDMP standard. Each of the roles specified in the IDMP standard will be subclasses of ingredient, signified by the proper code, and additional semantics for those roles, such as the connections to reference substances can be modeled directly for those roles that require that link in the graph. Elements in white are classes in the ontology. Elements in blue are instances, in this case, of codes.

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This becomes more complicated when defining the notion of a substance as an active ingredient in a given product, as in some cases the strength is required, and in others, a reference strength may be required. See Pattern: Representing Reference Substances, Reference Strength, and the Basis of Strength, including in Different Jurisdictions - REVIEWAPPROVED for further refinement with respect to modeling the basis of strength in the context of a given pharmaceutical product that is authorized for marketing or investigational use in a specific jurisdiction.

Example Instantiation of the Model Pattern

Figure 4, below, provides a partial example (with some details elided) of the representation of a chemical substance as an active ingredient with its strength. This example is also encoded in the set of examples provided with the ontology. Note that the elements in white are classes in the ontology. Elements in blue are instances of those classes, and in purple are literal values.

Figure 4. Example partial diagram for the substance amlodipine besylate as an active ingredient of the product Norvasc 

Note that this pattern does not cover complexities such as the basis of strength, which are addressed in more detail on Pattern: Representing Reference Substances, Reference Strength, and the Basis of Strength, including in Different Jurisdictions - REVIEWAPPROVED. These complexities require more complete coverage of the relationships between a product and its constituents in the context of a specific marketing authorization in a given jurisdiction.

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