# Concepts Representing a Substance or its Modifications

<mark style="color:$danger;">**This Editorial Guide is used for Education Purposes Only. It is used in the Authoring Courses and Certifications. It is based on the January 2026 Editorial Guide.**</mark>

## Overview

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 |Substance| hierarchy. Existing concepts will only be retained where there is a specific requirement and will be modeled as a child of |Metabolite (substance)|. See [Metabolites](https://docs.snomed.org/education/snomed-ct-education-editorial-guide/readme/authoring/domain-specific-modeling/substance/substance-naming-and-modeling-conventions/guidelines-for-specific-substance-types/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 [Substance Groupers Based on Structure](https://docs.snomed.org/education/snomed-ct-education-editorial-guide/readme/authoring/domain-specific-modeling/substance/substance-naming-and-modeling-conventions/guidelines-for-substance-hierarchy-grouper-concepts/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

<table data-header-hidden><thead><tr><th width="223.09765625">Semantic tag</th><th>(substance)</th></tr></thead><tbody><tr><td><strong>Semantic tag</strong></td><td>(substance)</td></tr><tr><td><strong>Definition status</strong></td><td>Primitive</td></tr><tr><td><p><strong>Attribute:</strong></p><p><strong>Is modification of</strong></p></td><td>Range: &#x3C; 105590001 |Substance (substance)|</td></tr></tbody></table>

## Exemplar

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

<figure><img src="https://3063935683-files.gitbook.io/~/files/v0/b/gitbook-x-prod.appspot.com/o/spaces%2FSZh4aZdgpviXMYp37bCy%2Fuploads%2Fgit-blob-f6f4e08480043dcebb0d1bb75ef92343d732849b%2Fimage%20(254).png?alt=media" alt=""><figcaption></figcaption></figure>

The following illustrates the **inferred** view for 125691000 |Sotalol hydrochloride (substance)|:

<figure><img src="https://3063935683-files.gitbook.io/~/files/v0/b/gitbook-x-prod.appspot.com/o/spaces%2FSZh4aZdgpviXMYp37bCy%2Fuploads%2Fgit-blob-6ddaa45ba6463551a18f0b764d3b3025cd6d7519%2Fimage%20(255).png?alt=media" alt=""><figcaption></figcaption></figure>

### Guidelines for the use of 738774007 | Is modification of (attribute)|

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

* For example,
  * Morphine hydrochloride (substance)

<figure><img src="https://3063935683-files.gitbook.io/~/files/v0/b/gitbook-x-prod.appspot.com/o/spaces%2FSZh4aZdgpviXMYp37bCy%2Fuploads%2Fgit-blob-a9d02b2c2940287a45b6375d154bc6abc62f1c3b%2Fimage%20(256).png?alt=media" alt=""><figcaption></figcaption></figure>

* For example,
  * Fluorothymidine (18-F) (substance)

<figure><img src="https://3063935683-files.gitbook.io/~/files/v0/b/gitbook-x-prod.appspot.com/o/spaces%2FSZh4aZdgpviXMYp37bCy%2Fuploads%2Fgit-blob-5e73a151f18f058034041400d05d452fa55c3f4d%2Fimage%20(257).png?alt=media" alt=""><figcaption></figcaption></figure>

Hydrates have an 738774007 | Is modification of (attribute)| relationship to the unspecified salt.

* For example,
  * Caffeine hydrate (substance) IS MODIFICATION OF Caffeine (substance).

This is the **stated** view:

<figure><img src="https://3063935683-files.gitbook.io/~/files/v0/b/gitbook-x-prod.appspot.com/o/spaces%2FSZh4aZdgpviXMYp37bCy%2Fuploads%2Fgit-blob-39c148cc614507917badbfb4af06af9d629df7f9%2Fimage%20(258).png?alt=media" alt=""><figcaption></figcaption></figure>

This is the **inferred** view:

<figure><img src="https://3063935683-files.gitbook.io/~/files/v0/b/gitbook-x-prod.appspot.com/o/spaces%2FSZh4aZdgpviXMYp37bCy%2Fuploads%2Fgit-blob-7241a2cc7acd4beb45e9d598bca6c0ee22bd6672%2Fimage%20(259).png?alt=media" alt=""><figcaption></figcaption></figure>

For example,

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

This is the **stated** view:

<figure><img src="https://3063935683-files.gitbook.io/~/files/v0/b/gitbook-x-prod.appspot.com/o/spaces%2FSZh4aZdgpviXMYp37bCy%2Fuploads%2Fgit-blob-ccd8e6511d661d8a9de72ab8d83dd5b226c12da6%2Fimage%20(260).png?alt=media" alt=""><figcaption></figcaption></figure>

This is the **inferred** view:

<figure><img src="https://3063935683-files.gitbook.io/~/files/v0/b/gitbook-x-prod.appspot.com/o/spaces%2FSZh4aZdgpviXMYp37bCy%2Fuploads%2Fgit-blob-e904c3924b392e8fdacfcf4080eeb64fefc513a7%2Fimage%20(261).png?alt=media" alt=""><figcaption></figcaption></figure>

<figure><img src="https://github.com/SNOMED-Documents/snomed-editorial-guide/blob/main/authoring/substance/images/174691495%20(1).png" alt=""><figcaption></figcaption></figure>

For example,

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

This is the **stated and inferred** view.

<figure><img src="https://3063935683-files.gitbook.io/~/files/v0/b/gitbook-x-prod.appspot.com/o/spaces%2FSZh4aZdgpviXMYp37bCy%2Fuploads%2Fgit-blob-71e819acb254cf2cce325976b118c31effbadb33%2Fimage%20(262).png?alt=media" alt=""><figcaption></figcaption></figure>

***

Anhydrous salts have an 738774007 | Is modification of (attribute)| relationship to the unspecified salt.

* For example,
  * Theophylline anhydrous (substance) IS MODIFICATION OF Theophylline (substance).

This is the **stated** view:

<figure><img src="https://3063935683-files.gitbook.io/~/files/v0/b/gitbook-x-prod.appspot.com/o/spaces%2FSZh4aZdgpviXMYp37bCy%2Fuploads%2Fgit-blob-13e0e66849477afaa20a7817949d8a2f7fbb5213%2Fimage%20(263).png?alt=media" alt=""><figcaption></figcaption></figure>

This is the **inferred** view:

<figure><img src="https://3063935683-files.gitbook.io/~/files/v0/b/gitbook-x-prod.appspot.com/o/spaces%2FSZh4aZdgpviXMYp37bCy%2Fuploads%2Fgit-blob-9a816c99f3b878a8dfd4c1a5a2938ea76489d2a1%2Fimage%20(264).png?alt=media" alt=""><figcaption></figcaption></figure>

The salts are modeled with an 738774007 | 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.

<figure><img src="https://3063935683-files.gitbook.io/~/files/v0/b/gitbook-x-prod.appspot.com/o/spaces%2FSZh4aZdgpviXMYp37bCy%2Fuploads%2Fgit-blob-1d74a0a6e480c3327e3395e8412c39575468d9bb%2Fimage%20(265).png?alt=media" alt=""><figcaption></figcaption></figure>

Liposomal preparations are modifications of the chemical substance.

* For example,
  * Daunorubicin citrate liposome (substance)|

<figure><img src="https://3063935683-files.gitbook.io/~/files/v0/b/gitbook-x-prod.appspot.com/o/spaces%2FSZh4aZdgpviXMYp37bCy%2Fuploads%2Fgit-blob-a8fdc40c4ab950def2839026521e9e987abd07b4%2Fimage%20(266).png?alt=media" alt=""><figcaption></figcaption></figure>

Pegylated substances are modeled with |s modification of (attribute)| generic 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 |Turoctocog alfa pegol (substance)|

<figure><img src="https://3063935683-files.gitbook.io/~/files/v0/b/gitbook-x-prod.appspot.com/o/spaces%2FSZh4aZdgpviXMYp37bCy%2Fuploads%2Fgit-blob-c927ad5ccfc85983b2890b3568cf2facea4ddab8%2Fimage%20(267).png?alt=media" alt=""><figcaption></figcaption></figure>

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.

* For example,
  * 414246008 |Fenofibrate micronized (substance)|

<figure><img src="https://3063935683-files.gitbook.io/~/files/v0/b/gitbook-x-prod.appspot.com/o/spaces%2FSZh4aZdgpviXMYp37bCy%2Fuploads%2Fgit-blob-ca88bf0ec37aa67c8775f04777225e9dd79d74e4%2Fimage%20(268).png?alt=media" alt=""><figcaption></figcaption></figure>

Grouper concepts should not be targets of an 738774007 | Is modification of (attribute)| relationship.

In general, an 738774007 | Is modification of (attribute)| is not applicable to prodrugs. 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 a modification of the substance salicylic acid.

{% hint style="info" %}
When a prodrug is an esterified form of substance, there should be an 738774007 | Is modification of (attribute)| relationship between the substance and its esterified form.

For exemplar,

* 715220007 |Tenofovir alafenamide (substance)|
* 89678001 |Cefuroxime axetil (substance)|
  {% endhint %}

738774007 | Is modification of (attribute)| is not applicable:

* Between a glycan and its glycoconjugate.
  * For example, 259289005 |Trimethylene glycol (substance)| is not a modification of 52086008 |Glycol (substance)|.
* 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.
* Between a chemical element and its salt.
  * For example, 387307005 |Calcium carbonate (substance)| is not a modification of |Calcium (substance)|.

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