This section of the document provides guidance for specific types of substances.

This section includes concepts that represent flap substances used in flap surgery. The concepts in this subhierarchy are used to define:

Flap composition

• For example,

  • bone, skin, muscle, myocutanous, osteocutaneous

Flap blood supply

Substance concepts that contain terms such as “fractionated” or “unfractionated” are not created in the Substance hierarchy. "Unfractinated" should not be included when referring to the "entire substance" or "whole substance"; it is implied. "Fractionated" usually refers to a separation technique or process.

Modeling

• Use antivenom, not antivenin, for FSNs and Preferred Terms. Synonyms containing antivenin are not created routinely but may be created upon request.

• FSNs should be based on the scientific name if there is a one-to-one correspondence. Naming conventions for polyvalent antivenoms (effective against multiple organisms) will not comply with this naming convention and will be evaluated on a case-by-case basis. Preferred Terms are based on the common name.

• Synonyms based on the scientific name should be created in most cases.

Useful reference: Current version of WHO Guidelines for the Production, Control and Regulation of Snake Antivenom Immunoglobulins

Pattern:

• X antivenom (substance), where X = scientific name of organism

For example,

• Chironex fleckeri antivenom (substance)

Pattern:

• Y antivenom, where Y = Common name of organism

For example,

• Australian box jellyfish antivenom

Exception

• When there is no common name for the organism, the PT will match the FSN

Pattern:

• A synonym that matches FSN (If not used Preferred term; see notes above)

For example,

• Chironex fleckeri antivenom

Additional synonyms (e.g., when other legitimate synonyms exist for Organism name) are applicable and are evaluated on a case-by-case basis

For example,

• Deadly sea wasp antivenom

The following illustrates the stated view of 699514008 |Chironex fleckeri antivenom (substance)|:

Modeling

Pattern: "Antibody to" + Antibody target

Note: An antibody target can be an antigen or another antibody.

For example,

• Antibody to nuclear antigen (substance)

• Antibody to thyroglobulin immunoglobulin G (substance)

Pattern: Antibody target + "antibody"

For example,

• Nuclear antibody or Thyroglobulin immunoglobulin G antibody

Pattern: A synonym that matches FSN

For example,

• Antibody to nuclear antigen

• Antibody to thyroglobulin immunoglobulin G

Pattern: Antibody target + "Ab"

For example,

• Nuclear Ab

• Thyroglobulin IgG Ab

Additional synonyms:

• Add a description containing antibody target + "autoantibody"

  • Nuclear autoantibody

  • Thyroglobulin IgG autoantibody

Many extracted substances in SNOMED CT are not specific to either the part of the plant (root, seed, leaf, etc.) or the form (powder, dry or soft extract, etc.). The specific part of the plant should be known and documented when using these substances in modeling medicinal products. The less specific descriptions may find use in hierarchies besides Pharmaceutical / biologic product (product), such as the need to record an adverse reaction to a substance where the full details are unknown. While the most specific information is encouraged, all levels of specificity can be represented in SNOMED CT.

Naming pattern:

FSN: [Scientific name of source organism] <part of plant> extract (substance)

PT: [Common name of organism] <part of plant> extract

SYN: [Scientific name of source organism] <part of plant> extract

Extracts that include form

For extracts that include form (such as dry), the form should follow the source in the FSN and the corresponding SYN. The PT can have the form either in front of or following the source, whichever is prevailing in the literature.

• For example,

  • FSN: Betula dry extract (substance)

  • PT: Dry birch extract

Preferred references for plant scientific and common names include the following:

• Integrated Taxonomic Information System

• Catalogue of Life

Thermo Fisher Scientific may be consulted for allergens.

The Global Substance Registration System (GSRS) is a good resource for substance names (INN, chemical names) but not necessarily the best for synonyms.

Some requests are for extracts of which the genus is too broad, while the requirement for the species is too specific. In these cases, the common name can be used; a scientific name is not used.

• For example,

  • If the requested concept is for blueberry extract, there is no single genus and species that identifies the blueberry plant. The Vaccinium genus includes cranberry, ligonberry, and other berry plants in addition to blueberry. There are multiple blueberry species. Therefore, the concept can be created for blueberry extract without a scientific name. The common name has a case sensitivity indicator of ci.

See related section at

Though an extract is derived from a substance, it is not a type of that substance.

• For example,

• |Ginkgo biloba extract (substance)| would not have a parent of |Ginkgo biloba (substance)|.

Overview

Fragments are created as siblings of the intact/whole/entire substance.

“Intact” should not be included when referring to the "entire substance" or "whole substance"; it is implied.

Alpha and beta sub-units should be the children of the entire substance, where "nicked" substances and fragments should be the siblings.

INN should be used for the Preferred Term where they exist.

Modeling

Pattern:

• X fragment (substance)

• X subunit (substance)

For example,

• Corticotropin, big fragment (substance)|

• Thyrotropin beta subunit (substance)

Pattern:

• X fragment

For example,

• Corticotropin, big fragment

• Thyrotropin beta subunit

Bound substances Overview

Creation of substance concepts that contain “bound” is limited to the measurement of biological substances (Observable entities, evaluation procedures, LOINC collaboration project) or to report their level (clinical findings).

Where the substance is "bound" the molecule to which the substance is bound to may be specified in the term.

Modeling

Pattern: Bound X (substance)

For example,

• Bound insulin (substance)

• Protein bound iodine (substance)

• Albumin bound thyroxine (substance)

Pattern: Bound X (substance)

For example,

• Bound insulin

• Protein bound iodine (substance)

• Albumin bound thyroxine (substance)

The following illustrates the stated and inferred view:

Overview

Within the substances hierarchy in SNOMED CT there are a number of substances where that is either a mix of isomers of a single chemical, a racemic mix or a single isomer.

• Omeprazole and Esomeprazole

• Cetirizine and Levocetirizine

• Loratadine and Desloratadine

Each of these substances will all need to be represented in SNOMED CT as separate concepts to support the representation of active ingredients in SNOMED CT and should be represented as sibling concepts without any SNOMED CT relationship created between the two substances.

The following illustrates the hierarchy view for Omeprazole and Esomeprazole:

Acids substance concepts should be modeled with a structural parent concept.

Salts should be modeled with a conjugate base as parent (if one exists, otherwise they are modeled with a structural parent). Salts may have an Is modification of (attribute) relationship to the conjugate acid where a specific use case is identified. See examples of such use cases at .

Conjugate base concepts (e.g., valproate, pamidronate, etidronate) should only be created where a specific use case is identified, for example, when required to support the definition of other concepts in the terminology.

Conjugate bases should be created as separate concepts - not added as synonyms to the corresponding acid concept.

New instances of substance concepts containing the word salt will not be added. The existing concepts will be reviewed, and if possible, will be replaced by equivalent compounds.

Concepts specifying a particular physical state (e.g. liquid, solid, fumes, vapor, crystal, foam) of a substance should be represented as the sibling for the unspecified substance and also have a parent concept that relates to the structure of the substance.

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.

Creation of substance concepts that contain terms such as “free” (or "unbound" or "unconjugated") is limited to the measurement of biological substances (Observable entities, evaluation procedures, LOINC collaboration project) or to report their level (clinical findings). These concepts are created as siblings of the base concepts with a "substance X and X derivatives" or "X and X compound" as common supertype.

Overview

Groupers based on structural properties of the substance that are deemed to be clinically useful will be included in the Substance hierarchy.

For example,

• Benzodiazepine (substance)

• Quinolone (substance)

Modeling

The following illustrates the stated and inferred view.

Use the following pattern for the FSN. Groupers are expressed in the singular, i.e., compound not compounds.

Examples of substances that represent a structural grouper:

• Organic nitrogen compound (substance)

• Halide compound (substance)

• Triazine derivative (substance)

• Copper and/or copper compound (substance)

Where the same word is used to identify both a group of substances with a particular chemical structure and a particular chemical substance, the following terming for the FSN is used for the substance grouper concept.

Substance with X structure (substance)

For example,

• Substance with tetracycline structure (substance)

• Substance with cresol structure (substance)

• Substance with benzene structure (substance)

Use the following pattern for the Preferred Term.

For example,

• Organic nitrogen compound

• Halide compound

• Triazine derivative

• Copper and/or copper compound

Where the same word is used to identify both a group of substances with a particular chemical structure and a particular chemical substance the following pattern will be used for PT the substance grouper concept.

Substance with X structure

For example,

• Substance with tetracycline structure

• Substance with cresol structure

• Substance with benzene structure

Additional synonyms are not allowed unless explicitly identified as an exception in the editorial guidelines.

Browser view of 299979007 |Organic nitrogen compound (substance)|

Browser view of 767209009 |Copper and/or copper compound (substance)|

Browser view of 766224008 |Substance with cresol structure (substance)|

Modeling

Hydates are modeled with an 738774007 | Is modification of (attribute)| relationship to the substance with unspecified hydration.

For example,

• Ferrous oxalate dihydrate (substance) is modification of → Ferrous oxalate

• Caffeine hydrate (substance) is modification of → Caffeine

• Zinc sulfate heptahydrate (substance) is modification of → Zinc sulfate

Pattern:

• X hydrate (substance)

• X dihydrate (substance)

• X monohydrate (substance)

For example,

• Copper sulfate pentahydrate (substance)

Pattern:

• X hydrate

• X dihydrate

• X monohydrate

For example,

• Copper sulfate pentahydrate

The following illustrates the inferred view.

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

Anhydrous compounds have an 738774007 | Is modification of (attribute)| relationship to the unspecified substance, i.e., where the level hydration is not specified.

For example,

• Sodium carbonate anhydrous (substance) is modification of → Sodium carbonate

• Theophylline anhydrous (substance) is modification of → Theophylline

Pattern:

• X anhydrous (substance)

For example,

• Theophylline anhydrous (substance)

Pattern:

• X anhydrous

For example,

• Theophylline anhydrous

Anhydrous X

The following illustrates the inferred view.

|Theophylline anhydrous (substance)| IS MODIFICATION OF |Theophylline (substance)|

Overview

Substance concepts should, where possible, be modeled with either a structural parent or one that denotes source or origin.

Modeling

FSN, PT or Synonym should not contain "- dietary" context in descriptions

FSN, PT or Synonym should not contain brand or trade names.

Culinary name should be used for the FSN and PT when referring to meat products and food, e.g., Beef dripping (substance), Pork sausage (substance).

If there are additional adjectives such as baked, boiled, fried, lean, minced, low-fat, roast, or stewed, these adjectives should proceed the name of source organism, e.g., Fried beef steak (substance), Tinned fish (substance).

Pattern:

• X (substance)

For example,

• Betel nut (substance)

• Wheat dextrin (substance)

• Tinned fish (substance)

Pattern:

• X

For example,

• Betel nut

• Wheat dextrin

• Tinned fish

Pattern: scientific name if appropriate

For example,

• Areca catechu

The following illustrates the stated and inferred view.

The following illustrates the stated and inferred view.

Previously, SNOMED CT represented ions and electrolytes as separate concepts. Although the two terms are subtly different, there is considerable overlap in their definitions, and they seem to be used interchangeably in medicine. The Substances Redesign Project Group considered this issue and determined the following:

• Ions should be modeled as child concepts of the substance.

• A second parent (in addition to X (substance)), that indicates the concept is an ionized substance, should be modeled.

A metabolite is a substance created or utilized during metabolism, the process by which the body breaks down food, drugs, chemicals, or its own tissues (e.g., fat, muscle). Metabolites are differentiated from derivatives, that are compounds synthesized by modifying precursor compounds and are important in discovery of new drugs (e.g., molecules with improved efficacy, reduced toxicity, or enhanced pharmacokinetic profiles), materials science (e.g., polymers with altered properties), and agrochemicals (e.g., potent pesticide).

Concepts representing Metabolites of X will be considered for inclusion based upon project requirements.

Overview

A recombinant (A new entity e.g., gene, protein, cell, or individual that results from genetic recombination) or synthetic/semi-synthetic substance (of, relating to, or produced by chemical or biochemical synthesis; especially: produced artificially) is similar in structure (but not identical to the naturally occurring substance). It should be created as a sibling of the naturally occurring substance.

A substance that is part of (e.g. dander) or is derived from (e.g. Insulin) an organism (human or non-human) is identical and should be created as a child of the naturally occurring substance.

Modeling

“Recombinant”, “Synthetic”, or “Semi-synthetic” should precede the name of the substance

The source organism name should precede the name of the substance

• An exception to this rule is the naming of DNA, RNA, rRNA, antibody, Immunoglobulin, and antigen of organisms, which should follow the guideline specified for antibodies and antigens

• For some non-human sources, there are different ways of referring to the source organism:

  • The common name of the organism e.g. pig, cow, horse, mouse, sheep

Additional adjectives (such as labeled, Iodinated) should proceed the name of source organism

• For example,

  • Lente human insulin (substance)

  • Iodinated (125-I) human serum albumin (substance)

If a concept includes “recombinant” or “synthetic” as well as a source organism, “recombinant” or “synthetic” should precede the source organism name

• For example,

  • Recombinant bovine growth hormone (substance)

Pattern:

• [Source organism] X (substance)

• Recombinant X (substance)

• Synthetic X (substance)

For example,

• Human antithrombin III (substance)

• Recombinant thrombin (substance)

• Synthetic steroid (substance)

Pattern:

• [Source organism] X

• Recombinant X

• Synthetic X

For example,

• Human antithrombin III

• Recombinant thrombin

• Synthetic steroid

The naming of DNA, RNA, rRNA, antibody, Immunoglobulin, and antigen of organisms should follow the specific guideline for this type of substances.

Stated view of 411973001 |Bovine thrombin (substance)|

Representation of radioactive isotopes

Modeling

Pattern:

• [name of isotope]-[atomic number] (substance)

For example,

• Gallium-67 (substance)

Pattern:

[name of isotope]-[atomic number]

For example,

• Gallium-67

Pattern:

• [atomic number]-[chemical symbol]

For example,

• 67-Ga

The following illustrates the hierarchy view:

The following illustrates the stated and inferred view:

Superscripts should not be used in either Fully Specified Name, Preferred Term, or synonyms.

Parentheses should be used to delineate the atomic number and chemical symbol from the rest of the terming; this aligns with INN.

Pattern: [name of isotope] ([atomic number]-[chemical symbol]) [salt] (substance)

For example,

• Gallium (67-Ga) citrate (substance

Pattern: [name of isotope] ([atomic number]-[chemical symbol]) [salt]

For example,

• Gallium (67-Ga) citrate

The following illustrates the stated and inferred view:

Superscripts should not be used in either Fully Specified Name, Preferred Term, or synonyms.

The Fully Specified Name should explicitly state that a component was “labeled” by a radioisotope in the FSN. Do not use “with”, “and”, or “tagged”.

Omit the word “labeled” from the PT; keep a synonym to match the FSN.

The following illustrates both the stated and inferred view:

Overview

This section includes concepts that represent

• Antigen of organism

• Antibody to organism

• Immunoglobulin G, M, A, E, D antibody to organism

Organism above includes substances derived from an organism, for example, feather or protein.

When referring to an organism name, while the Linnean taxon ranks (such as genus) are not included, the subspecies variants (such as biotype and serotype) are included in the naming. This avoids ambiguity when the same number or letter is used to refer to different organism variants.

• For example,

  • Without mentioning the specific variant (serogroup vs. serotype) and the nomenclature system (Danish vs. American), Streptococcus pneumoniae 48 can refer to the following:

    • Streptococcus pneumoniae Danish serotype 48 (which is equivalent to Streptococcus pneumoniae American serotype 82)

The antigen name is usually derived from the biological name of the organism as opposed to the disease or infection that the organism may cause and/or that the vaccine may provide immunization for.

Pattern:

• Antigen of X organism (substance)

For example,

• Antigen of Filaria (substance)

• Antigen of Alternaria alternata protein (substance)

Pattern:

• X organism antigen

For example,

• Filaria antigen

• Alternaria alternata protein antigen

Exception:

• Preferred term for |Antigen of live attenuated Mycobacterium bovis| is |Bacillus Calmette-Guerin antigen|

1. Pattern: A synonym that matches FSN

   1. For example,

      1. Antigen of Filaria

There is a requirement for the inclusion of characteristic technologies that are essential for distinguishing between different antigen variants that are used in manufacturing vaccine products, e.g., live attenuated, inactivated, or subunit antigens. Antigen variants are evaluated for:

• References such as WHO, CDC, UpToDate, vaccine package inserts

• Inclusion in the international release vs. national extensions

• Hierarchy they belong to: Substance or Product

To prevent the creation of transient or short-lived viral strain content, the International Release will not create specific viral variant strains or their corresponding antigen substance concepts when those variants have only brief or limited existence. For the purpose of defining clinical drugs or vaccine products in the International Release, stable higher-level parent virus or antigen concepts should be used instead. National Release Centers (NRCs) that require representation of specific viral variants for local regulatory or clinical use cases may create such concepts within their extensions.

"Antigen of X" is in scope for the international release and is modeled in the Substance hierarchy. It is a generic grouper concept and subsumes all instances of antigen variants related to Organism X.

• X refers to a bacteria, virus, fungus, or parasite except when antigen refers to the organism “toxin/toxoid”, where it can only apply to a bacteria.

“Antigen of live attenuated X” is in scope for the international release and is modeled in the Substance hierarchy as a direct child of |Antigen of X|.

• It refers to attenuated whole cell bacteria or whole virus where the strains are made less virulent so infection is usually inapparent or very mild. It may be used in the creation of vaccine products for certain patient groups, and hence, is of clinical significance.

• The following subtypes are also in scope for the international release and are modeled in the Substance hierarchy as direct children of |Antigen of live attenuated X|. In the following examples, human and bovine refer to source organisms which are differentiated from the organism producing antigen, i.e., Rotavirus.

  • “Live attenuated human X”, e.g., Antigen of live attenuated human Rotavirus serotype G1P[8]

“Antigen of inactivated whole X” is in scope for the international release and is modeled in the Substance hierarchy as a direct child of Antigen of X.

• It refers to the killed version of the organism that causes a disease.

• As of the July 2020 release, the word "whole" is added to all new and existing concepts referring to "Antigen of inactivated X" to further clarify the differentiation between "Antigen of inactivated whole organism" (referring to a killed organism as a whole) and "Antigen of organism [subunit]" (referring to subparts of an organism).

“Antigen of acellular X” is in scope for the international release and is modeled in the Substance hierarchy as the direct child of "Antigen of X".

• "Antigen of acellular X", when it exists, can only apply to a bacteria.

“Antigen of X [subunit]” is in scope for the international release and is modeled in the Substance hierarchy as the direct child of “Antigen of X”.

• Subunit antigens differ from inactivated whole-cell antigens by referring only to the antigenic parts of the pathogen. These parts are necessary to elicit a protective immune response. The word “inactivated” does not need to be part of the name unless it is referring to a whole cell or a whole virus, i.e., for descriptions referring to a subunit, the word inactivated will be omitted as redundant.

• [Subunit] refers to a sub-part of an organism i.e. a specific, isolated protein of the pathogen, a recombinant protein (made by recombinant DNA techniques), an inactivated toxin (toxoid), or a capsular polysaccharide/oligosaccharide coating of an encapsulated bacterium:

  • "Antigen of X [protein/recombinant protein]" is in scope for the international release and is modeled in the Substance hierarchy.

When referring to Organism parts/subunits:

• Referring to more than one subunit (e.g., combined protein such as Bordetella pertussis FIM 2 and FIM 3 antigen) would not be acceptable for the Substance hierarchy; the combined protein needs to be modeled at the product level with more than one active ingredient.

• Abbreviated organism subunit names such as "Corynebacterium diphtheriae CRM197 protein", are not allowed in a fully specified name (and similar synonym). The FSN and similar synonym should only include the spelled-out terms, i.e., "Corynebacterium diphtheriae cross-reacting material 197 protein".

• Abbreviated organism part names are allowed in a preferred term (and other synonyms). The abbreviations do not need to be accompanied by the fully expanded term, which is an exception to the general naming guidelines on abbreviations and acronyms in the SNOMED CT Editorial Guide.

Inclusion of vaccine manufacturing techniques and/or residuals in antigen names is generally out of scope for the international release. However, exceptions can be made for applicable use cases.

• "Antigen of X grown in nervous tissue" or "Antigen of X grown in cellular line" is acceptable for inactivated Rabies antigens grown in brain tissue or cell lines and is included in the international release, considering the difference in the adverse reactions that they cause. If and when created:

  • "Antigen of X grown in cellular line" will be a grouper and other subgroups will be added as needed, e.g., "grown in Human diploid cell".

  • "Antigen of X grown in nervous tissue" should indicate the specific type of nervous tissue, e.g., brain.

• Antigen of X

  • Antigen of live attenuated X

  • Antigen of inactivated whole X

The following illustrates the stated and inferred view:

Pattern:

• Antibody to X organism (substance)

For example,

• Antibody to Bebaru virus (substance)

Pattern:

• X organism antibody

For example,

• Bebaru virus antibody

1. Pattern: A synonym that matches FSN

   1. For example,

      1. Antibody to Bebaru virus

Additional synonyms (e.g., when a legitimate synonym exists for Organism name, such as common names) are applicable.

The following illustrates the stated and inferred view:

Pattern:

• Immunoglobulin G, M, A, E, D antibody to X organism (substance)

For example,

• Immunoglobulin M antibody to Clostridium difficile (substance)

• Immunoglobulin G antibody to Juglans (substance)

Pattern:

• X organism IgG, M, A, E, D

For example,

• Clostridium difficile IgM

• Walnut IgG

  • Walnut is the common name for Juglans.

1. Pattern: A synonym that matches FSN

   1. For example,

      1. Immunoglobulin M antibody to Clostridium difficile

Additional synonyms (e.g., when a legitimate synonym exists for Organism name, such as common names) are applicable.

• For example,

  • Juglans IgG

    • Juglans is the scientific name for walnut.

The following illustrates the stated and inferred view:

When authoring in this domain, this is the approved attribute and allowable range.

Domain Information for Substance

Previously, the substances hierarchy in SNOMED CT was organized using a number of different axes, some of which did not comply with the terminological principle of being always true. This resulted in incorrect inferences both within the substance hierarchy and in other hierarchies where substances were used to define concepts. To avoid this, the substances hierarchy has been organized by characteristics that are always true (e.g., chemical structure). For substances where the structure is unknown or the substance is heterogeneous, other characteristics that are always true should be used as parent concepts within the substances hierarchy.

The current substances top level hierarchy includes a number of grouper concepts that are role- or use case-based. The proposal is to create a substances top level hierarchy as below.

The grouper concepts that are retained as top level substance concepts will need review of their descendants, but ultimately, it should provide a consistent hierarchy.

There are similarities in the scope of ISO 11238 Health informatics – Identification of medicinal products – Data Elements and Structures for the Unique Identification and Exchange of Regulated Information on Substances and the SNOMED CT substances revision, since both consider a substance to be defined by properties such as molecular structure, and not by how it is formulated or used.

IDMP groups substances as being one of five types of single substances:

• (simple) chemical

• protein/peptide

• nucleic acid

• polymer

or they are classified as a mixture.

In IDMP, the definition of a mixture is much broader that would be perceived by clinical users. IDMP defines starches as mixtures, and also compounds, such as isophane insulin and gentamicin sulfate, as mixtures. This broad definition for mixtures would mean that many of the SNOMED CT substances would be classified as mixtures. These IDMP types are not represented in SNOMED CT, since they are not mutually exclusive and are open to some interpretation. The IDMP documentation does provide guidance on the selection of the correct type for a substance but also acknowledges that a single substance may have two separate type definitions. In addition, the use of the word “mixture” in the substances hierarchy is to be discouraged, since as a general scope statement, SNOMED CT does not include combination substances that are a mixture of more than one individual chemical even when the two exhibit a synergistic effect, e.g., tazobactam and piperacillin.

Changes to SNOMED CT concept model in the future to permit the use of concepts within the products hierarchy to model disorder and findings concepts means that these combined substances concepts will no longer be required, and so, will be inactivated at that time.

The scope of substances in SNOMED CT is broader than that of IDMP, since the definition of regulated products is not the only use case supported by the SNOMED CT substances hierarchy.

IDMP classes are used to identify which features could/should be identified as defining. This is different from the SNOMED CT requirement to identify top level concepts to support a hierarchy that provides a logical structure for substance concepts.

IDMP makes a distinction between Substance and the more closely defined Specified Substance. Substances are “any matter of defined composition that has discrete existence, whose origin may be biological, mineral or chemical".

1. Specified Substances are "defined by groups of elements that describe multi-substance materials or specifies further information on substances relevant to the description of Medicinal Products".

2. Specified substances include mixture substances, substances defined by pharmacopoeial specification or substances where a particular manufacturing process is specified.

In order for SNOMED CT to support the IDMP work, whose primary goal is to define unambiguously all substances present in regulated products, it is necessary for both the concepts that are IDMP Substances and those that are IDMP Specified Substances to be present in the SNOMED CT Substance hierarchy. Stereoisomers, hydrates, and solvates are included in the SNOMED CT substances hierarchy as concepts, as well as concepts to represent their base chemical in the SNOMED CT substance hierarchy. Since both IDMP Substances and IDMP Specified Substances are candidate concepts to be used in the ingredient role attributes, it does not add value in the definition of these concepts to separately identify IDMP Substances and IDMP Specified Substances in SNOMED CT and would likely cause confusion where substance concepts are used to define concepts outside the scope of IDMP and the medicinal product hierarchy.

Overview

This section of the document provides both general terming and modeling guidance for substance concepts.

Modeling

Descriptions should be singular, not plural.

• Exception: Fumes should be expressed in the plural (i.e., fumes as opposed to fume).

Descriptions should not include additional descriptors that reference a use case.

• For example,

  • Non-pharmaceutical

Some regulatory agencies may use prefixes or suffixes to distinguish between different manufacturers of a single substance but these are not used in SNOMED CT; the INN name is used.

• For example,

  • The FDA uses "ado-trastuzumab"; the INN for this substance is "trastuzumab". The INN is reflected as the US and GB names in SNOMED CT International Release, because the prefix represents a specific manufacturer's product.

  • The FDA uses "emicizumab-kxwh" and "vestronidase alfa-vjbk"; the INN for these substances are "emicizumab" and "vestronidase alfa". The INN is reflected as the US and GB names in SNOMED CT International Release, because the suffix represents a specific manufacturer's product.

Substance concepts should not include a strength.

Substance concepts should not include a dose form or use case.

• Exception: Substances that do not have stain as part of their approved name but are used as stains and are subtypes of 397165007 |Stain (substance)|

  • For example,

    • 25351006 |Fluorescein sodium stain (substance)|

The FSN is aligned with the INN; the Preferred Terms are aligned with USAN and BAN (BAN almost always aligns with the INN). The Preferred Term in the US dialect variation must be given the acceptability of Acceptable (A) in the GB dialect and vice versa.

For isomers, the INN names use the expanded prefix, e.g., levo or dextro, and so should be used for the FSN and Preferred Term.

Changes to descriptions allocated to existing substance concepts may impact the terming of medicinal product concepts and so should be undertaken with caution.

Based on recommendation by the International Protein Nomenclature Guidelines:

• Usage of the term 'protein' in a protein name should be avoided if not necessary, especially when the name includes terms such as "factor", "enzyme", "inhibitor", or "regulator".

• Enzyme names commonly end with 'ase' (aminoacylase, arginase, etc.). The term ‘protein’ should not be appended to the enzyme names.

For case sensitivity assignment:

• Greek alphabetical terms in substance concepts have been made case insensitive.

• For substance terms that have a single letter, either a single lower case letter or a single upper case letter, the case sensitivity should reflect either CS if the single capital letter or single lower case letter is at the beginning of the term, or cI if the single capital letter or single lower case letter is contained within an otherwise case insensitive term.

• Proper names in substance terms should begin with a capital letter.

The following defining attributes correspond to the Substance Attribute Summary table.

Has disposition

This attribute enables the creation of an association between a substance concept and a disposition. A disposition is defined as a behavior that a substance will exhibit or participate in, given the appropriate context.

Is modification of

This attribute indicates that the concept is a structural modification of another concept, and that the substance's intrinsic physicochemical properties remain unchanged.

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Overview

The hierarchy, 726711005 |Disposition (disposition)|, was created to support the remodeling of the Substance hierarchy. The concepts in this hierarchy are used as the attribute value for the |Has disposition (attribute)| for concepts in the Substance hierarchy, to sufficiently define grouper concepts representing dispositions, and to sufficiently define concepts in other SNOMED CT hierarchies. To provide adequate context to differentiate concepts in this hierarchy from similar concepts in other existing SNOMED CT hierarchies, a new (disposition) semantic tag was created.

See also:

• Medicinal Product Groupers; Groupers Based on Disposition

• Substance Groupers Based on Disposition

The following words should be avoided unless specifically identified as an exception in the editorial guidelines.

• agent

• analog

• and

• and/or

Exceptions:

• Alkylating agent (disposition)

• Chelating agent (disposition)

• receptor agonist or partial agonist

• receptor antagonist or partial antagonist

• enzyme inhibitor or enzyme system inhibitor

Patterns:

• X receptor agonist (disposition)

• X receptor antagonist (disposition)

• X inhibitor (disposition)

Example of receptor agonist:

• Dopamine receptor agonist (disposition)

• Opioid receptor agonist (disposition)

• Opioid receptor partial agonist (disposition)

Example of receptor antagonist:

• Beta-adrenergic receptor antagonist (disposition)

• Histamine receptor antagonist (disposition)

• Opioid receptor antagonist (disposition)

Example of inhibitor (enzyme):

• Acetylcholinesterase inhibitor (disposition)

• Phosphodiesterase 5 inhibitor (disposition)

Example of inhibitor (enzyme system):

• Hydrogen/potassium adenosine triphosphatase enzyme system inhibitor (disposition)

• Selective serotonin reuptake inhibitor (disposition)

Example of activator:

• Plasminogen activator (disposition)

Patterns:

• X receptor agonist

• X receptor antagonist

• X inhibitor

Example of receptor agonist:

• Dopamine receptor agonist

• Opioid receptor agonist

Example of receptor antagonist:

• Beta-adrenergic receptor antagonist

• Histamine receptor antagonist

• Opioid receptor antagonist

Example of enzyme inhibitor:

• Acetylcholinesterase inhibitor

• Phosphodiesterase 5 inhibitor

• Centrally acting acetylcholinesterase inhibitor

Example of enzyme system inhibitor:

• Proton pump inhibitor

• Selective serotonin reuptake inhibitor

Example of enzyme inducer:

• Plasminogen activator

Exceptions:

• Preferred terms may reflect the common clinical description for a disposition.

  • Example:

    • |Hydrogen/potassium adenosine triphosphatase enzyme system inhibitor (disposition)| has Preferred Term |Proton pump inhibitor|

Synonyms are not allowed unless explicitly identified as an exception.

Pattern:

• X (disposition)

Example:

• Growth factor (disposition)

• Cytokine (disposition)

• Carcinogen (disposition)

• Potassium channel blocker (disposition)

Pattern:

• X

Example:

• Growth factor

• Cytokine

• Carcinogen

• Potassium channel blocker

Synonyms are not allowed unless explicitly identified as an exception.

Pattern:

• X (disposition)

Example:

• Alkylating agent (disposition)

• Chelating agent (disposition)

Pattern:

• X

Example:

• Alkylating agent

• Chelating agent

Synonyms are not allowed unless explicitly identified as an exception.

The following illustrates the stated and inferred view:

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 .

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 .

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.

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

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

• For example,

  • Morphine hydrochloride (substance)

• For example,

  • Fluorothymidine (18-F) (substance)

• For example,

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

This is the stated view:

This is the inferred view:

For example,

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

This is the stated view:

This is the inferred view:

For example,

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

This is the stated and inferred view.

• For example,

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

This is the stated view:

This is the inferred view:

• For example,

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

• For example,

  • Daunorubicin citrate liposome (substance)|

• For example,

  • 785674001 |Turoctocog alfa pegol (substance)|

• For example,

  • 414246008 |Fenofibrate micronized (substance)|

Dried gels have an |Is modification of (attribute)| relationship to the gel substance.

• For example, 768558006 |Dried aluminium hydroxide gel (substance)| has an |Is modification of (attribute)| relationship of |Algeldrate (substance)|.

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.

• 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.

Overview

Groupers based on both structure and disposition that are deemed to be clinically useful and that can be sufficiently defined will be included in the |Substance| hierarchy.

Note: This section applies to concepts representing a single structural parent and a single disposition. It does not apply concepts representing more than one structural parent or disposition.

Modeling

The following illustrates the stated and inferred view for grouper concepts based on both structure and disposition.

Use the following pattern for the FSN, with X representing the structure and Y representing the disposition. The FSN should align with the FSN for the substance grouper and disposition used as the stated parent and attribute value respectively.

• X with Y mechanism of action (substance)

For example,

• Piperazine derivative with histamine H1 receptor antagonist mechanism of action (substance)

• Substance with dihydropyridine derivative structure and calcium channel blocker mechanism of action (substance)

• Substance with organophosphorus structure and acetylcholinesterase inhibitor mechanism of action (substance)

Use the following pattern for the Preferred Term, with X representing the structure and Y representing the disposition. The FSN should align with the FSN for the substance grouper and disposition used as the stated parent and attribute value respectively.

• X Y

For example,

• Piperazine derivative histamine H1 receptor antagonist

• Dihydropyridine derivative calcium channel blocker

• Organophosphorus acetylcholinesterase inhibitor

A synonym to match the FSN is not required.

Additional synonyms are allowed only if they are consistent with the synonyms for the corresponding structure grouper and disposition.

General Assumptions and Requirements

Decisions regarding requirements, applicable use cases, scope, terming, and modeling guidelines are made based on requests submitted by user community and in consultation with subject matter experts, associated Project Groups, and relevant credible references.

Top level concepts in the hierarchy will primarily be grouper concepts for both the stated and inferred views.

Concepts representing dispositions in the |Substance| hierarchy shall be sufficiently defined using proximal primitive modeling methodology unless explicitly noted as an exception in the editorial guidelines.

This section applies to the |Substance| hierarchy in the International Release:

Substances that support the modeling of concepts in other SNOMED CT hierarchies, including but not limited to: Medicinal product, Clinical finding, Procedure, Observable Entity, and Specimen

In the SNOMED CT substance hierarchy, there are a large number of grouper concepts. Currently, groupers within the substances can be considered to be structural groupers, disposition groupers, or role based.

The intent is to build the SNOMED CT substance hierarchy along structural or disposition groupers and use a |Has disposition (attribute)| relationship to define grouper concepts in the substance hierarchy. Grouper concepts that do not reference structural or disposition properties of a substance should not be included within the substance hierarchy and existing role concepts are considered for relocation outside of the substance hierarchy.

Groupers that organize substances by their chemical structure are used as the main hierarchy for substances. Where substances are heterogeneous and do not have a single identifiable chemical structure, such as those of biological origin, it may be more appropriate to organize them by source.

In the context of substances, a disposition is “a behavior that a substance will exhibit or participate in, given the appropriate context.” This context-based definition of disposition would allow us to assign |Has disposition (attribute)| values that are necessarily true, even though the substance does not exhibit the disposition in all contexts.

Role based groupers are associated with a particular purpose or outcome. Roles are a function of the way the substance is formulated or presented and so may not be applicable to all products containing that substance, which may lead to incorrect classification of concepts using role groupers as attribute values. At this time, the existing Substance role groupers will remain in situ with no change. However, additional concepts of this type will not be created, and requests for new instances will be rejected.