The Principles that guide the specific decisions on individual maps or particular groups of concepts are described below.
The following mapping principles were used to develop the map.
The map was developed based on the principle that the source and target codes of 'equivalent' maps must be an exact semantic match. However, the characteristics of a given PDF in Standard Terms may not exactly match the logical definition of a SNOMED CT concept, as long as the "mismatch" does not cause a semantic conflict. Indeed in some cases, the mismatch may enhance the match. Here are some examples:
The SNOMED CT FSN is apparently narrower than the EDQM Term based on the intended site characteristic but is an exact match based on the definition; this usually occurs when the EDQM Term uses a grouper concept for the characteristic, whereas the SNOMED CT uses the specific concept for the attribute.
EDQM intended site "cutaneous/transdermal" whereas SNOMED CT has explicitly either cutaneous or transdermal as appropriate.
EDQM intended site "oromucosal" whereas SNOMED CT has explicitly either buccal, sublingual, etc., as appropriate.
The SNOMED CT PDF uses a different administration method than the EDQM Term, but the difference is not considered clinically significant.
EDQM administration method for "rectal foam" is the very generic "administration," whereas SNOMED CT has the administration method "apply".
A characteristic/attribute mismatch must respect the semantics of the Term: for example, the EDQM PDF "oral gel" is used for medicinal products that will be swallowed, whereas the SNOMED CT "conventional release oral gel" has an administration method of "apply" is not appropriate since application implies use on a body surface. (Note, this SNOMED CT concept is currently subject to a change request to resolve this and allow a semantic match)
For more information on the semantic representation of codes in the source and target terminologies, please refer to the next page.
Several groups of EDQM PDFs have greater granularity than the similar dose forms used in the definition of clinical drugs in the SNOMED CT International edition. In order to provide a good semantic match, especially for the description of RCDs, SNOMED CT has the more granular dose form concepts modeled such that the more granular PDF concepts can be grouped under a less granular parent concept.
In order to achieve the full definition of PDFs with this greater granularity, some additional basic dose forms have been created in SNOMED CT. This occurs particularly (but not exclusively) with oral dose forms:
Hard and soft capsules:
Whilst the prescription process is rarely interested in the difference between hard capsules (two halves of a firm shell, one of which "slips over" the other to seal) and soft capsules (filled and sealed in a single process), it is of importance to the dispensing/administration process because there is a difference in divisibility and administration (open the capsule and sprinkle), and therefore this granularity is needed to describe RCDs in national extensions.
Coated and film-coated concepts; molded and compressed lozenges:
For oral PDFs, powders and granules are differentiated, whereas, for parenteral products for human use, they are not; although EDQM does have the term: "Granules for suspension for injection" it appears not to be used to describe any medicinal products.
As a general principle. if there is a pharmaceutical dose form that undergoes a transformation to another pharmaceutical dose form, the transformed PDF concept should be available in SNOMED CT International content even if there are no CDs that directly require it. This is because even though the RCD would use the manufactured dose form, some extensions may also model "administrable clinical drugs" or equivalent concepts and require the administrable dose form.
For example, "Powder for intravesical solution" will transform to "Intravesical solution"; both must exist as PDF concepts.
Wherever possible, patterns for administration method have been used for all PDF concepts, and these contribute to ensuring concepts have an exact semantic match.
Both drops and spray liquid dose forms are present in EDQM and in SNOMED CT. In EDQM, some terms use "drops" or "spray" as the basic dose form, and terms that use the more usual "solution/suspension/emulsion/dispersion" basic dose forms. The former terms are original and are not recommended for use in new medicinal product authorisations.
In SNOMED CT, there are also unspecified "drops" or "spray" concepts, where the basic dose form is not given (nor is a transformation, since there cannot be the certainty that a transform will not occur), and the definition is supported by the administration method (instill for drops and spray for sprays); these concepts are used to describe international clinical drugs. SNOMED CT also has more granular concepts with the basic dose form and transformation specified to support a direct match to the EDQM concepts; however, these concepts do not relate to each other directly in the hierarchy because of the lack of basic dose form.
The administration method of "instill" is also used for liquid installations, liquids administered to body cavities (bladder instillation, etc.).
Several EDQM PDFs are described as "washes" (for example, "ear wash") where the semantic is of the liquid (containing one or more medicinal substances) flowing over or through the site, flushing and cleansing it but not remaining in or at the site for a prolonged period. To obtain semantically matching concepts, SNOMED CT has PDFs that have the administration method of "rinse/wash". Irrigation solutions also use the administration method of "rinse/wash".
Other EDQM PDFs are described as for bathing, where the intended site is in contact with the liquid (containing one or more medicinal substance(s)) - often by immersion - for a prolonged period.
Finding the boundary between some dose forms and the products and medical devices, which are physical objects in SNOMED CT, can be challenging. Medicinal products contain one or more substances that are intended "for treating or preventing disease, with the view to making a medical diagnosis or to restore, correct or modify physiological functions"1, so in any situation where there is a requirement to "contain" those substances for administration, a pharmaceutical dose form should exist. This means that, for example, PDFs for dialysis solutions are required since these "contain" the substances that pull the toxins from the patient's blood into the dialysate.
In this section, we compare the different approaches used by EDQM and SNOMED CT to represent the meaning of pharmaceutical dose forms. This understanding was used to develop the principles for defining semantic matches between EDQM and SNOMED CT dose forms.
An example of the source EDQM pharmaceutical dose form terminology is shown below, taken from the Standard Terms browser:
The EDQM PDF concept has a name (term) and a (text) definition; these are the most important pieces of data to understand the concept's meaning; this is given in English. In the "Translations" tab, the name of the dose form is given in the other European languages.
Exclusion statements may be found either in the main Definition (as in the first example) or in the Comment section (as in the second example below). These are provided not as explicit exclusion from a higher level concept but as implementation guidance” for marketing authorisation applicants to support them when selecting a PDF to describe their product. This means that, despite these exclusion statements, an EDQM higher-level PDF concept is semantically equivalent to a SNOMED CT higher-level (grouper) concept PDF.
Within the EDQM definition, there may be statements that are more "descriptional" than definitional that have to be evaluated for the mapping.
Although when describing abstract concepts such as clinical drugs, this level of granularity is not considered, it is frequently used in the description of RCDs since there are pharmacopoeial differences in the dose forms. By having the greater granularity in the basic dose form attribute, RCDs can be fully described using the exactly matching PDF, and more abstract concepts can be grouped using the parent grouper basic dose form.
For example, for the "Granules" term, the text says this dose form is a "Solid single-dose or multidose preparation consisting of solid, dry aggregates of powder particles that are sufficiently resistant to withstand handling. Granules are intended for oral use to release active substance(s) in the gastrointestinal fluids at a rate depending essentially on the intrinsic properties of the active substance(s) (conventional release). They may be swallowed as such and/or chewed before swallowing, and some may also be dissolved or dispersed in water or another suitable liquid before oral administration. 'Granules for oral solution' and 'Granules for oral suspension' are excluded". The principle is that if the intention is that the dose form will be dissolved or dispersed, then the more explicit dose forms should be used ('Granules for oral solution' and 'Granules for oral suspension') whereas if the context is that the granules may be dissolved or dispersed but this is not required, then "no transform" is the transform characteristic.
Similarly, the intention is that the granules will be swallowed; they may be chewed prior to swallowing or swallowed directly. Although EDQM has both "chewing" and "swallowing" as Administration Method characteristics, "chewing" is not the primary intention and should not be considered definitional. Note that this is in contrast to SNOMED CT, where the attributes, including Administration Method, are definitional (and indeed should be reflected in the Fully Specified Name - within the parameters of the Editorial Guide for Pharmaceutical Dose Forms).
In the concept below "to obtain a local effect" is stated in the definition. The definition of a PDF is concerned with it being the thing that "formulates or encapsulates or contains the active and inactive ingredient substances either at the point of supply (the manufactured dose form) or at the point of administration (the administrable dose form)"; therefore there should be no consideration of what happens to the active substance(s) once the administration has been made and no consideration of what or where their effect will occur. It is not possible to state accurately for any one PDF whether its effect (either therapeutically desired or undesired) will be "local" or "systemic"; for example, there are oral tablets that have no systemic effect (e.g. nystatin). Therefore, even if "for local effect" (or "for systemic effect") is part of either the definition or the comment for an EDQM PDF concept, it will not be deemed part of the semantic of the concept for mapping.
The characteristic values for a PDF should also be examined whilst remembering that currently, the attributes of a PDF concept in EDQM are **NOT **definitional for the concept. Therefore, there is no requirement for a complete match between the characteristic values of an EDQM PDF and the logical definition of a SNOMED CT PDF.
As described in the Introduction, the EDQM Standard Terms have their roots deep in the European Pharmacopoeia and this continues to guide their development. This is most clear when describing terms with multiple possible intended sites of administration. For safety reasons, terms with different intended sites (where no site predominates in the usage) will only be accepted if the sites share the same microbiologic (and sometimes other, e.g. pH) requirements. For example, the term "powder for solution for injection, infusion or inhalation", although it has been used to describe some medicinal products (for example, colistimethate products) it is rejected as a Standard Term because of the different specifications for solutions to be inhaled compared to parenterally administered solutions.
The definition of "prolonged release" is clear that this is "achieved by a special formulation design and/or manufacturing method" - and therefore, by implication, not by the substance. Therefore products containing substances like "haloperidol decanoate", "insulin isophane", or "insulin zinc suspension" should not have prolonged release dose forms as it is the modification of the substance that makes its release longer than the unmodified or simply modified substance, not the dose form.
If EDQM accepts a request for a new pharmaceutical dose form for use with a veterinary product, this will be marked as for "human and veterinary use" unless the dose form is specifically formulated for a "veterinary only" intended site - such as a beak or a rumen. For example, "beak dip" is marked as veterinary only. This means that there are some PDFs in the EDQM Standard Terms that have never been used to describe medicinal products for human use.
In SNOMED CT, the fully specified name (FSN) ‘unambiguously ’ represents the meaning of the concept. In addition:
For "defined" concepts: the set of defining relationships (the "concept model" - see below) sufficiently represents the logical meaning of the FSN
For "primitive" concepts: the set of relationships represents part of the logical meaning of the FSN (the totality of the meaning is captured in the FSN)
Some text definitions exist, especially for primitive concepts used as attributes in the concept model. For example, the "method of administration" attribute value concepts have a textual definition.
SNOMED CT PDFs are “qualifier values” because they are used as attributes in the medicinal product concept model, but they are still full concepts in their own right.
In SNOMED CT, the "stated view" shows the concept as it is directly authored; the "inferred view" adds in relationships to other (grouper) concepts based on the SNOMED CT logic rules.
The parent (grouping) concept 736542009 | Pharmaceutical dose form (dose form) | has no attributes (and is therefore marked as “primitive”), but the child concepts - the PDF concepts themselves, have a concept model:
Although polyhierarchical, the SNOMED CT browser will display PDF concepts in the inferred view in a hierarchy based on the value of the intended site of the dose form, with a grouper concept acting as the parent:
