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The substance redesign project has made a number of decisions regarding the representation of a substance and its modifications.

  1. Modification indicates that the concept is a structural modification of another concept, where the intrinsic physicochemical properties of the substance do not change.
  2. The intrinsic physicochemical properties do not encompass non-intrinsic characteristics of a substance, such as toxicity, bioavailability, or extended release (in the case of medicinal products).
  3. Modification concepts that exist to group modifications or derivatives of a specific substance are not to be created.
  4. Metabolite groupers in the substances hierarchy are considered roles. No further concepts of this format will be created in the substances |Substance| hierarchy.  Existing concepts will only be retained where there is a specific requirement and will be modeled as a child of the concept Metabolite |Metabolite (substance)|. See relative section elsewhere in this document Metabolites.
  5. Structural groupers that reference modifications as a chemical group will be retained. Where the structural group name also refers to a specific chemical the grouper will be re-termed “Substance with X structure”.  See relative section elsewhere in this document Substance Groupers Based on Structure.
  6. There is no requirement to introduce a new semantic tag in order to distinguish concepts representing a substance or its modifications from any other type of concept in the |Substance| hierarchy.

Modeling

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Semantic tag

(substance)

Definition status

900000000000074008 |Necessary but not sufficient concept definition status (core metadata concept)|

Attributes

None

Primitive

Attribute:

Is modification of

Range:  <105590001 |Substance (substance)|

Exemplar

The following illustrates the stated view view of 125691000 |Sotalol hydrochloride (substance)|:

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The following illustrates the inferred view for concepts that are a modification. view for 125691000 |Sotalol hydrochloride (substance)|:

Guidelines for the use

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of
Concept
t738774007 |Is modification of (attribute)|

Substances may have zero to many Is modification of attribute(s).

For example,

    • Morphine hydrochloride (substance)

For example,

    • Fluorothymidine (18-F) (substance)



For example,

    • Doxepin hydrochloride (substance)

Hydrates have a IS MODIFICATION OF an 

Concept
t738774007 |Is modification of (attribute)|
relationship to the unspecified salt.

For example,

    • Caffeine hydrate (substance) IS MODIFICATION OF Caffeine (substance)

This is the stated view

...

:

Image Modified

This is the 

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inferred view:

For example, 

    • Clindamycin hydrochloride monohydrate (substance) IS MODIFICATION OF Clindamycin hydrochloride (substance).  

        This is the stated view:

Image Modified

This is the inferred view:

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For example, 

    • Calcium lactate pentahydrate (substance) IS MODIFICATION OF Calcium lactate (substance)

This is the stated and inferred view.

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Anhydrous salts have a IS MODIFICATION salts have an 

Concept
t738774007 |Is modification of (attribute)|
relationship to the unspecified salt.

For example,

    • Theophylline anhydrous (substance) IS MODIFICATION OF Theophylline (substance).

This is the stated view:

Image Modified

This is the inferred view:

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The salts are modeled with an IS Modification OF an 

Concept
t738774007 |Is modification of (attribute)|
the acid substance.

For example,

    • Pamidronate monosodium (substance) IS MODIFICATION OF Pamidronic acid (substance). This is the stated and inferred view.

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Liposomal preparations are modifications of the chemical substance.

For example,

    • Daunorubicin citrate liposome (substance)|

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Pegylated substances should be modeled with |Is s modification of (attribute)| generic substance–if substance, if such a substance has been made available; not all pegylated medicinal substances have a non-pegylated form as the non-pegylated form may have been too immunogenic or too toxic.

       For example, 785674001  

    • 785674001 |Turoctocog alfa pegol (substance)|

       Image Modified

Concepts specifying a particular physical form (e.g. micronized, macrocrystal, microsphere) should have a parent concept that relates to the structure of the substance and also an Is modification of (attribute) relationship to the unspecified substance concept.

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Grouper concepts should not be targets of an "Is_modification”

Concept
t738774007 |Is modification of (attribute)|
relationship.

In general, an an 

Concept
t738774007 |Is modification of (attribute)|
is not applicable to prodrugs. For example, aspirin is not generally considered as a modification of the substance salicylic acid.   This is because there is no requirement for the |Has active ingredient (attribute)| of medicinal products containing prodrug substances to use any relationship to the active substance to manage relationships within the medicinal product hierarchy. 

For example, aspirin is not generally considered as a modification of the substance salicylic acid.

Warning

When a prodrug is an esterified form of substance, there should be an “is_modification” an 

Concept
t738774007 |Is modification of (attribute)|
relationship between the substance and its esterified form.Exemplar:

For exemplar,

    • 715220007 |Tenofovir alafenamide (substance)|
    • 89678001 |Cefuroxime axetil (substance)|

Concept
t738774007 |Is modification of (attribute)|
"Is_modification” relationship is not applicable between :

  • Between a glycan and its glycoconjugate.

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    • For example, 259289005 |Trimethylene glycol (substance)|

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    • is not

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    • a modification of 52086008 |Glycol (substance)|.

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  • To genetic engineering process variations (e.g. Somatropin(epr), Somatropin(rbe), or Somatropin(rmc) as SNOMED CT does not generally differentiate substances based on production process.

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  • Between a chemical element and its salt.

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    • For example, 387307005 |Calcium carbonate (substance)| is not a modification of |Calcium (substance)|.