How Granular Can a Dose Form Be Described? Considering EDQM Standard Terms for a Global Terminology
2. Materials and Methods
3.1. Describing EDQM as It Is
- Release characteristics (four values): conventional, prolonged, delayed, modified;
- Transformation (six values): dilution, dissolution, dispersion, mixing, no transformation, unknown;
- Intended Site (25 values): example: auricular; ocular; oral (see Supplementary File for full list);
- Administration method (19 values): example: application; inhalation; injection.
3.2. Potential Problems Identified and Approaches to Improvements
3.3. Construction of a New Basic File
3.4. Construction of the Small Ontology
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
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|(a) Analysis Not Taking “Systemic/Local” into Account|
|Number of Analysis||Basic Dose Form (PDF)||State of Matter (PDF)||Basic Dose Form (ADF)||State of Matter (ADF)||Transformation (TRAC)||Release Characteristics (RC)||Intended Site Split (ISI-s)||Administration Method (AMEC)||Systemic/Local||Total Number of Unique Combinations (UC)||Unique Combinations (UC) with 1 Occurence||Unique Combinations (UC) with 2+ Occurences||Sum of Occurences in Unique Combinations 2+||Sum of Occurences in UC2+ and in UC1|
|(b) Same Analysis but Now Taking “Systemic/Local” into Account|
|Descriptors: Basic Dose Form (BDF) and State of Matter (SOM) of Pharmaceutical Dose Form (PDF) and Administrable Dose Form (ADF)|
|Transformation (TRAc):(6 values): dilution, dissolution, dispersion, mixing, no transformation, unknown.|
|Release Characteristics (RC):(4 values): conventional, prolonged, delayed, modified.|
|Intended Site (ISI-s):(25 values): example: auricular; ocular; oral (see Supplementary file for full list).|
|Administration Method (AMEc):(19 values): example: application; inhalation; injection. (see supplementary file for full list).|
|Systemic/local: (4 values):systemic, local, local/systemic, unknown|
|Analysis 1:Taking all descriptors and all characteristics into account|
|Analysis 2:Taking the descriptors of the administrable dose form and all characteristics into account|
|Analysis 3:Taking only all characteristics into account|
|Analysis 4:Taking the Basic Dose Form of the Administrable Dose Form, RC, ISI-s, and AMEc into account (mimicing the FDA/WHO_UMC pilot approach)|
|Unique combinations (UC) with 1 occurence:a specific combination of the values of descriptors and/or characteristics, represented by one PDF|
|Can be considered as a measure of granularity of the dose form terminology and an indicator of congruence with the textual definition|
|Unique combinations with 2 or more occurences (UC2+):a specific combination of the values, represented by two or more PDFs|
|Can be considered as a measure of aggregation for ontologic class creation|
|Sum of occurences in UC2+:the number of PDFs grouped in unique combinations of values with 2 or more occurences of dose forms|
|Can be considered as an additional measure of aggregation for ontological class creation|
|Total number of unique combinations:sum of UC and UC2+|
|Can be considered as an addtional measure of granularity of the dose form terminology|
|Check:the sum of UC and the sum of the occurences in UC2+ must always be 428 (grey cells)|
|Auricular dose form||Oral solid dose form|
|Auricular/nasal dose form||Oral semi-solid dose form|
|Auricular/nasal/ocular dose form||Oral drops dose form|
|Auricular/ocular dose form||Oral liquid dose form|
|CUTANEOUS||Oral effervescent or dispersible dose form|
|Cutaneous dose form||Oral/rectal dose form|
|Cutaneous/transdermal dose form||ORAL, MODIFIED-RELEASE|
|Cutaneous/nasal dose form||Oral gastro-resistant dose form|
|Cutaneous/oromucosal dose form||Oral prolonged-release dose form|
|Cutaneous/parenteral dose form||Other oral modified-release dose form|
|Dental dose form||Oromucosal spray dose form|
|ENDOCERVICAL||Oromucosal solid dose form|
|Endocervical dose form||Oromucosal prolonged-release dose form|
|EXTRACORPOREAL||Oromucosal liquid dose form|
|Extracorporeal dose form||Oromucosal gargling/mouthwash dose form|
|EXTRACORPOREAL/PARENTERAL||Sublingual dose form|
|Dialysis dose form||PARENTERAL|
|GASTRIC||Implantation prolonged-release dose form|
|Gastric dose form||Injection prolonged-release dose form|
|GASTROENTERAL||Injection dose form|
|Gastroenteral dose form||Infusion dose form|
|INTRAPERITONEAL||Infusion/injection dose form|
|Intraperitoneal dose form||PULMONARY|
|INTRAUTERINE||Vapour dose form|
|Intrauterine dose form||Nebuliser dose form|
|Intrauterine device||Pressurised inhalation dose form|
|INTRAVESICAL||Inhalation dose form|
|Intravesical/intraurethral dose form||Medicinal gas dose form|
|OCULAR||Endotracheopulmonary instillation dose form|
|Ocular semi-solid dose form||RECTAL|
|Ocular drops dose form||Rectal systemic dose form|
|Ocular rinsing dose form||Rectal local dose form|
|Ocular intraocular dose form||TRANSDERMAL|
|Ocular prolonged-release dose form||Transdermal prolonged-release dose form|
|NASAL||Transdermal dose form|
|Nasal spray dose form||VAGINAL|
|Nasal solid or semi-solid dose form||Vaginal prolonged-release dose form|
|Nasal drops dose form||Vaginal dose form|
|Endosinusial dose form||Vaginal device|
|Nasal/ocular/pulmonary dose form||MISCELLANEOUS|
|Radiopharmaceutical dose form|
|Wound dressings prolonged-release dose form|
|Ungrouped dose form|
|1. The relationship between transformable Pharmaceutical dose forms (hence, the manufactured dose forms) and their administrable dose forms (and their state of matter and basic dose form) needs to be made more explicit in the EDQM dose form Terminology|
2. The role of the characteristics in the EDQM dose form terminology, albeit not definitional, can be more then informational and may become the basis of systematic revision and ontology creation.
3. The value sets of the characteristics need to be slightly revised, taking into account multiplicity, systemic effect, and sublingual use. The coding system of the values needs to be corroborated and strengthened by adopting ISO/CEN norms for coding systems.
4. A new characteristic could be added, based on systemic and/or local effect. This would greatly facilitate the automated identification of polypharmacy as the concomitant use of 5 or more chronic drugs with systemic effect.
5. A simple ontology for dose forms may enable more rigorous standardization of dose forms in national regulatory agencies and facilitate semantic interoperability the alignment with other dose form terminologies, used in clinical care and research.
6. Standardization of national dose form identification to EDQM will require special training of regulatory experts in industry and agencies, and validation procedures.
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Vander Stichele, R.H.; Roumier, J.; van Nimwegen, D. How Granular Can a Dose Form Be Described? Considering EDQM Standard Terms for a Global Terminology. Appl. Sci. 2022, 12, 4337. https://doi.org/10.3390/app12094337
Vander Stichele RH, Roumier J, van Nimwegen D. How Granular Can a Dose Form Be Described? Considering EDQM Standard Terms for a Global Terminology. Applied Sciences. 2022; 12(9):4337. https://doi.org/10.3390/app12094337Chicago/Turabian Style
Vander Stichele, Robert H., Joseph Roumier, and Dirk van Nimwegen. 2022. "How Granular Can a Dose Form Be Described? Considering EDQM Standard Terms for a Global Terminology" Applied Sciences 12, no. 9: 4337. https://doi.org/10.3390/app12094337