Pharmaceutical Quality (Industry)
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Pharmaceutical Quality (Industry), published by HL7 International / Biomedical Research and Regulation. This guide is not an authorized publication; it is the continuous build for version 1.0.0 built by the FHIR (HL7® FHIR® Standard) CI Build. This version is based on the current content of https://github.com/HL7/uv-dx-pq/ and changes regularly. See the Directory of published versions

Impurities: synthetic data rendering - drug substance

The HTML rendering below shows a synthetic Quality data example for Common Technical Document (CTD) Module 3: Quality, section 3.2.S.3 Characterisation, subsection 3.2.S.3.2 Impurities.

This is the same data as in the example files here in xml and in json, presented for easier viewing. Hovering on words below will show the corresponding sections of the underlying data.

Bundle [documentation R4 R5 R6]
id: bundle-product-impurities-pq-ex2-sub
Profile: http://hl7.org/fhir/uv/pharm-quality/StructureDefinition/Bundle-product-impurities-pq
Type: collection
Impurities Report - Substance, on Stelbatolol

Substance - Stelbatolol [documentation R4 R5 R6]
id: substance1
fullUrl: urn:uuid:03d68d1c-162c-8b6e-70f9-647b0ea97adb
Name: Stelbatolol
Manufacturer
Found a parent (SubstanceDefinition/manufacturer, id: substance1 fullUrl: urn:uuid:03d68d1c-162c-8b6e-70f9-647b0ea97adb)
which is linked to this by resource.id
Organization [documentation R4 R5 R6]
id: substance-manufacturer
fullUrl: urn:uuid:062bf235-44e2-55c4-9213-bbe5e12d5620
- AAA Molybdenum Products, Inc.
Identifier: 3003040516 (urn:oid:2.16.840.1.113883.4.82)
Active: true
Name: AAA Molybdenum Products, Inc.
Type: Drug Substance Manufacture [drug-substance-manufacture] (http://terminology.hl7.org/CodeSystem/pharmaceutical-organization-type)
Contact
Address: 7233 W 116th Pl, Ste C, Broomfield, Colorado, 80020, USA

Table 1. Potential Process-Related Organic Impurities

Chemical Name / Descriptor Structure Molecular weight (g/mole) Category Impurity Characterization Method Summary Levels Observed in the API
R-enantiomer of stelbatalol
295.80 Chiral Impurity Enantiomeric purity by LC; Mass spectrometry ND
Impurity 1
344.4 Process impurity Organic impurities by HPLC Range: ND-0.2%
Impurity 2
459.58 Process impurity Organic impurities by LC Range: ND–0.3%
β-naphthol
144.173 Starting material, forced degradation product Organic impurities by HPLC; Chromatographic retention Observed only during stress studies
1-(Ethylamino)-3-(2-naphthyloxy)-2-propanol
245.32 Process intermediate, forced degradation product Impurity content by LC-MS; UV spectroscopy; NMR spectroscopy Observed only during stress studies


Table 2. Summary of (Q)SAR Results for All Known and Potential Mutagenic Impurities

Chemical Name / Descriptor Structure Origin in Process Bacterial Mutagenicity
Predictions or Knowledge 		Comments
Rule-Based (Q)SAR Statistical (Q)SAR ICH M7 Classification
R-enantiomer of stelbatalol
Enantiomer of API SM Negative Negative Class 5 Treated as non-mutagenic due to lack of alerting structure
Impurity 1
Step 1a Process Impurity Negative Negative Class 5 Treated as non-mutagenic due to lack of alerting structure
Impurity 2
Step 1a Process Impurity Negative Negative Class 5 Treated as non-mutagenic due to lack of alerting structure
β-naphthol
API Starting Material Negative Negative Class 5 Treated as non-mutagenic due to lack of alerting structure
1-(Ethylamino)-3-(2-naphthyloxy)-2-propanol
API Process Intermediate Positive Positive Class 2 Control at or below qualification threshold

Relationship
Type: Impurity Of [Impurity] (http://hl7.org/fhir/substance-relationship-type), Chiral Impurity [CH-IMP] (http://terminology.hl7.org/CodeSystem/impurity-type)
Impurity Origin: Enantiomer [enantiomer] (http://terminology.hl7.org/CodeSystem/impurity-origin) - Text: Enantiomer of API SM
Amount: ND
Found a parent (SubstanceDefinition/substanceDefinitionReference, id: substance1 fullUrl: urn:uuid:03d68d1c-162c-8b6e-70f9-647b0ea97adb)
which is linked to this by resource.id
Substance - R-enantiomer of stelbatalol [documentation R4 R5 R6]
id: impurityEnantiomer
fullUrl: urn:uuid:03d68d1c-162c-8b6e-80f9-647b0ea97ad1
Name: R-enantiomer of stelbatalol
Property
Type: Rule-based (Q)Sar [1233444] (http://hl7.org/fhir/uv/pharm-quality/CodeSystem/cs-substance-property-pq-example)
Value: Negative [negative] (http://hl7.org/fhir/uv/pharm-quality/CodeSystem/cs-substance-property-value-pq-example)
Property
Type: Statistical (Q)Sar [123555] (http://hl7.org/fhir/uv/pharm-quality/CodeSystem/cs-substance-property-pq-example)
Value: Negative [negative] (http://hl7.org/fhir/uv/pharm-quality/CodeSystem/cs-substance-property-value-pq-example)
Property
Type: ICH M7 Classification [123556] (http://hl7.org/fhir/uv/pharm-quality/CodeSystem/cs-substance-property-pq-example)
Value: Class 5 [class-5] (http://hl7.org/fhir/uv/pharm-quality/CodeSystem/cs-substance-property-value-pq-example)
Property
Type: Mutagenicity Comment [123557] (http://hl7.org/fhir/uv/pharm-quality/CodeSystem/cs-substance-property-pq-example)
Value: Treated as non-mutagenic due to lack of alerting structure
Molecular Weight
Amount: 295.80 g/mole [g/mol] (http://unitsofmeasure.org)
Characterization
Technique: Enantiomeric purity by LC
Characterization
Technique: Mass spectrometry
Structure
Representation
Found a parent (SubstanceDefinition/document, id: impurityEnantiomer fullUrl: urn:uuid:03d68d1c-162c-8b6e-80f9-647b0ea97ad1)
which is linked to this by resource.id
Document [documentation R4 R5 R6]
id: impurityEnantiomerdoc
fullUrl: urn:uuid:13d68d1c-162c-8b6e-80f9-647b0ea97ad1
Status: current
Content
Content Type: image/x-png
Relationship
Type: Impurity Of [Impurity] (http://hl7.org/fhir/substance-relationship-type), Process impurity [PR-IMP] (http://terminology.hl7.org/CodeSystem/impurity-type)
Impurity Origin: Process Impurity [process] (http://terminology.hl7.org/CodeSystem/impurity-origin) - Text: Step 1a Process Impurity
Amount: Range: ND-0.2%
Found a parent (SubstanceDefinition/substanceDefinitionReference, id: substance1 fullUrl: urn:uuid:03d68d1c-162c-8b6e-70f9-647b0ea97adb)
which is linked to this by resource.id
Substance - Impurity 1 [documentation R4 R5 R6]
id: impurity1
fullUrl: urn:uuid:03d68d1c-162c-8b6e-80f9-647b0ea97ad2
Name: Impurity 1
Property
Type: Rule-based (Q)Sar [1233444] (http://hl7.org/fhir/uv/pharm-quality/CodeSystem/cs-substance-property-pq-example)
Value: Negative [negative] (http://hl7.org/fhir/uv/pharm-quality/CodeSystem/cs-substance-property-value-pq-example)
Property
Type: Statistical (Q)Sar [123555] (http://hl7.org/fhir/uv/pharm-quality/CodeSystem/cs-substance-property-pq-example)
Value: Negative [negative] (http://hl7.org/fhir/uv/pharm-quality/CodeSystem/cs-substance-property-value-pq-example)
Property
Type: ICH M7 Classification [123556] (http://hl7.org/fhir/uv/pharm-quality/CodeSystem/cs-substance-property-pq-example)
Value: Class 5 [class-5] (http://hl7.org/fhir/uv/pharm-quality/CodeSystem/cs-substance-property-value-pq-example)
Property
Type: Mutagenicity Comment [123557] (http://hl7.org/fhir/uv/pharm-quality/CodeSystem/cs-substance-property-pq-example)
Value: Treated as non-mutagenic due to lack of alerting structure
Molecular Weight
Amount: 344.4 g/mole [g/mol] (http://unitsofmeasure.org)
Characterization
Technique: Organic impurities by HPLC
Structure
Representation
Found a parent (SubstanceDefinition/document, id: impurity1 fullUrl: urn:uuid:03d68d1c-162c-8b6e-80f9-647b0ea97ad2)
which is linked to this by resource.id
Document [documentation R4 R5 R6]
id: impurity1doc
fullUrl: urn:uuid:13d68d1c-162c-8b6e-80f9-647b0ea97ad2
Status: current
Content
Content Type: image/x-png
Relationship
Type: Impurity Of [Impurity] (http://hl7.org/fhir/substance-relationship-type), Process impurity [PR-IMP] (http://terminology.hl7.org/CodeSystem/impurity-type)
Impurity Origin: Process Impurity [process] (http://terminology.hl7.org/CodeSystem/impurity-origin) - Text: Step 1a Process Impurity
Amount: Range: ND–0.3%
Found a parent (SubstanceDefinition/substanceDefinitionReference, id: substance1 fullUrl: urn:uuid:03d68d1c-162c-8b6e-70f9-647b0ea97adb)
which is linked to this by resource.id
Substance - Impurity 2 [documentation R4 R5 R6]
id: impurity2
fullUrl: urn:uuid:03d68d1c-162c-8b6e-80f9-647b0ea97ad9
Name: Impurity 2
Property
Type: Rule-based (Q)Sar [1233444] (http://hl7.org/fhir/uv/pharm-quality/CodeSystem/cs-substance-property-pq-example)
Value: Negative [negative] (http://hl7.org/fhir/uv/pharm-quality/CodeSystem/cs-substance-property-value-pq-example)
Property
Type: Statistical (Q)Sar [123555] (http://hl7.org/fhir/uv/pharm-quality/CodeSystem/cs-substance-property-pq-example)
Value: Negative [negative] (http://hl7.org/fhir/uv/pharm-quality/CodeSystem/cs-substance-property-value-pq-example)
Property
Type: ICH M7 Classification [123556] (http://hl7.org/fhir/uv/pharm-quality/CodeSystem/cs-substance-property-pq-example)
Value: Class 5 [class-5] (http://hl7.org/fhir/uv/pharm-quality/CodeSystem/cs-substance-property-value-pq-example)
Property
Type: Mutagenicity Comment [123557] (http://hl7.org/fhir/uv/pharm-quality/CodeSystem/cs-substance-property-pq-example)
Value: Treated as non-mutagenic due to lack of alerting structure
Molecular Weight
Amount: 459.58 g/mole [g/mol] (http://unitsofmeasure.org)
Characterization
Technique: Organic impurities by LC
Structure
Representation
Found a parent (SubstanceDefinition/document, id: impurity2 fullUrl: urn:uuid:03d68d1c-162c-8b6e-80f9-647b0ea97ad9)
which is linked to this by resource.id
Document [documentation R4 R5 R6]
id: impurity2doc
fullUrl: urn:uuid:13d68d1c-162c-8b6e-80f9-647b0ea97ad9
Status: current
Content
Content Type: image/x-png
Relationship
Type: Impurity Of [Impurity] (http://hl7.org/fhir/substance-relationship-type), Starting material, forced degradation product [ST-IMP] (http://terminology.hl7.org/CodeSystem/impurity-type)
Impurity Origin: Starting Material [starting-material] (http://terminology.hl7.org/CodeSystem/impurity-origin) - Text: API Starting Material
Amount: Observed only during stress studies
Found a parent (SubstanceDefinition/substanceDefinitionReference, id: substance1 fullUrl: urn:uuid:03d68d1c-162c-8b6e-70f9-647b0ea97adb)
which is linked to this by resource.id
Substance - β-naphthol [documentation R4 R5 R6]
id: impurityNapthol
fullUrl: urn:uuid:03d68d1c-162c-8b6e-80f9-647b0ea97ad3
Name: β-naphthol
Code: 2-Naphthol [135-19-3] (http://terminology.hl7.org/CodeSystem/CAS)
Property
Type: Rule-based (Q)Sar [1233444] (http://hl7.org/fhir/uv/pharm-quality/CodeSystem/cs-substance-property-pq-example)
Value: Negative [negative] (http://hl7.org/fhir/uv/pharm-quality/CodeSystem/cs-substance-property-value-pq-example)
Property
Type: Statistical (Q)Sar [123555] (http://hl7.org/fhir/uv/pharm-quality/CodeSystem/cs-substance-property-pq-example)
Value: Negative [negative] (http://hl7.org/fhir/uv/pharm-quality/CodeSystem/cs-substance-property-value-pq-example)
Property
Type: ICH M7 Classification [123556] (http://hl7.org/fhir/uv/pharm-quality/CodeSystem/cs-substance-property-pq-example)
Value: Class 5 [class-5] (http://hl7.org/fhir/uv/pharm-quality/CodeSystem/cs-substance-property-value-pq-example)
Property
Type: Mutagenicity Comment [123557] (http://hl7.org/fhir/uv/pharm-quality/CodeSystem/cs-substance-property-pq-example)
Value: Treated as non-mutagenic due to lack of alerting structure
Molecular Weight
Amount: 144.173 g/mole [g/mol] (http://unitsofmeasure.org)
Characterization
Technique: Organic impurities by HPLC
Characterization
Technique: Chromatographic retention
Structure
Representation
Found a parent (SubstanceDefinition/document, id: impurityNapthol fullUrl: urn:uuid:03d68d1c-162c-8b6e-80f9-647b0ea97ad3)
which is linked to this by resource.id
Document [documentation R4 R5 R6]
id: impurityNaptholDoc
fullUrl: urn:uuid:13d68d1c-162c-8b6e-80f9-647b0ea97ad3
Status: current
Content
Content Type: image/x-png
Representation
Type: SMILES [SMILES] (http://hl7.org/fhir/substance-representation-format)
Representation: OC1=CC2=C(C=C1)C=CC=C2
Representation
Type: InChI [InChI] (http://hl7.org/fhir/substance-representation-format)
Representation: 1S/C10H8O/c11-10-6-5-8-3-1-2-4-9(8)7-10/h1-7,11H
Relationship
Type: Impurity Of [Impurity] (http://hl7.org/fhir/substance-relationship-type), Process intermediate, forced degradation product [INT-IMP] (http://terminology.hl7.org/CodeSystem/impurity-type)
Impurity Origin: Intermediate Material [intermediate-material] (http://terminology.hl7.org/CodeSystem/impurity-origin) - Text: API Process Intermediate
Amount: Observed only during stress studies
Found a parent (SubstanceDefinition/substanceDefinitionReference, id: substance1 fullUrl: urn:uuid:03d68d1c-162c-8b6e-70f9-647b0ea97adb)
which is linked to this by resource.id
Substance - 1-(Ethylamino)-3-(2-naphthyloxy)-2-propanol [documentation R4 R5 R6]
id: impurityPropanol
fullUrl: urn:uuid:03d68d1c-162c-8b6e-80f9-647b0ea97ad4
Name: 1-(Ethylamino)-3-(2-naphthyloxy)-2-propanol
Property
Type: Rule-based (Q)Sar [1233444] (http://hl7.org/fhir/uv/pharm-quality/CodeSystem/cs-substance-property-pq-example)
Value: Positive [positive] (http://hl7.org/fhir/uv/pharm-quality/CodeSystem/cs-substance-property-value-pq-example)
Property
Type: Statistical (Q)Sar [123555] (http://hl7.org/fhir/uv/pharm-quality/CodeSystem/cs-substance-property-pq-example)
Value: Positive [positive] (http://hl7.org/fhir/uv/pharm-quality/CodeSystem/cs-substance-property-value-pq-example)
Property
Type: ICH M7 Classification [123556] (http://hl7.org/fhir/uv/pharm-quality/CodeSystem/cs-substance-property-pq-example)
Value: Class 2 [class-2] (http://hl7.org/fhir/uv/pharm-quality/CodeSystem/cs-substance-property-value-pq-example)
Property
Type: Mutagenicity Comment [123557] (http://hl7.org/fhir/uv/pharm-quality/CodeSystem/cs-substance-property-pq-example)
Value: Control at or below qualification threshold
Molecular Weight
Amount: 245.32 g/mole [g/mol] (http://unitsofmeasure.org)
Characterization
Technique: Impurity content by LC-MS
Characterization
Technique: UV spectroscopy
Characterization
Technique: NMR spectroscopy
Structure
Representation
Found a parent (SubstanceDefinition/document, id: impurityPropanol fullUrl: urn:uuid:03d68d1c-162c-8b6e-80f9-647b0ea97ad4)
which is linked to this by resource.id
Document [documentation R4 R5 R6]
id: impurityPropanolDoc
fullUrl: urn:uuid:13d68d1c-162c-8b6e-80f9-647b0ea97ad4
Status: current
Content
Content Type: image/x-png