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SVG Files

Appendix 8: XML eCTD DTD

<?xml version="1.0" encoding="UTF-8"?>

<!-- Changes prior to Version 1.00 captured in file "Historical Changes.txt

Changes in version 3.1

- ID was changed to REQUIRED in the following four locations:

<!ENTITY % att " ID ID #REQUIRED xml:lang CDATA #IMPLIED">

<!ELEMENT leaf (title, link-text?)>

<!ATTLIST leaf

ID ID #REQUIRED <attlist continues>

<!ELEMENT xref EMPTY>

<!ATTLIST xref

ID ID #REQUIRED <attlist continues>

<!ELEMENT node-extension (title, (leaf | node-extension)+)>

<!ATTLIST node-extension

ID ID #REQUIRED

xml:lang CDATA #IMPLIED>

Changes in version 3.2

- Indication attribute was changed to REQUIRED in the following two locations:

<!ATTLIST m2-7-3-summary-of-clinical-efficacy %att;

indication CDATA #REQUIRED

<!ATTLIST m5-3-5-reports-of-efficacy-and-safety-studies %att;

indication CDATA #REQUIRED

- Since ID is only needed for files referenced in a LEAF, changed ID back to IMPLIED for:

<!ENTITY % att " ID ID #REQUIRED xml:lang CDATA #IMPLIED">

<!ELEMENT node-extension (title, (leaf | node-extension)+)>

<!ATTLIST node-extension

ID ID #REQUIRED

xml:lang CDATA #IMPLIED>

End of changes -->

<!ENTITY % att " ID ID #IMPLIED xml:lang CDATA #IMPLIED">

<!-- ============================================================= -->

<!-- Top-level element -->

<!-- ============================================================= -->

<!ELEMENT ectd:ectd (m1-administrative-information-and-prescribing-information?, m2-common-technical-document-summaries?, m3-quality?, m4-nonclinical-study-reports?, m5-clinical-study-reports?)>

<!ATTLIST ectd:ectd

xmlns:ectd CDATA #FIXED "http://www.ich.org/ectd"

xmlns:xlink CDATA #FIXED "http://www.w3c.org/1999/xlink"

xml:lang CDATA #IMPLIED dtd-version CDATA #FIXED "3.2"

>

<!-- ============================================================= -->

<!-- Leaf content -->

<!-- ============================================================= -->

<!ELEMENT leaf (title, link-text?)>

<!ATTLIST leaf

ID ID #REQUIRED

application-version CDATA #IMPLIED version CDATA #IMPLIED

font-library CDATA #IMPLIED

operation (new | append | replace | delete) #REQUIRED modified-file CDATA #IMPLIED

checksum CDATA #REQUIRED

checksum-type CDATA #REQUIRED

keywords CDATA #IMPLIED

xmlns:xlink CDATA #FIXED "http://www.w3c.org/1999/xlink"

xlink:type CDATA #FIXED "simple"

xlink:role CDATA #IMPLIED xlink:href CDATA #IMPLIED

xlink:show (new | replace | embed | other | none) #IMPLIED xlink:actuate (onLoad | onRequest | other | none) #IMPLIED xml:lang CDATA #IMPLIED

>

<!ELEMENT title (#PCDATA)>

<!ATTLIST title

ID ID #IMPLIED

>

<!ELEMENT link-text (#PCDATA | xref)*>

<!ATTLIST link-text ID ID #IMPLIED

>

<!ELEMENT xref EMPTY>

<!ATTLIST xref

ID ID #REQUIRED

xmlns:xlink CDATA #FIXED "http://www.w3c.org/1999/xlink"

xlink:type CDATA #FIXED "simple"

xlink:role CDATA #IMPLIED xlink:title CDATA #REQUIRED xlink:href CDATA #REQUIRED

xlink:show (new | replace | embed | other | none) #IMPLIED xlink:actuate (onLoad | onRequest | other | none) #IMPLIED

>

<!ELEMENT node-extension (title, (leaf | node-extension)+)>

<!ATTLIST node-extension ID ID #IMPLIED

xml:lang CDATA #IMPLIED

>

<!-- ============================================================= -->

<!-- CTD Backbone structures -->

<!-- ============================================================= -->

<!ELEMENT m1-administrative-information-and-prescribing-information (leaf*)>

<!ATTLIST m1-administrative-information-and-prescribing-information %att;

<!ELEMENT m2-common-technical-document-summaries (leaf*, m2-2-introduction?, m2-3-quality-overall-summary?, m2-4-nonclinical-overview?, m2-5-clinical-overview?, m2-6-nonclinical-written-and-tabulated-summaries?, m2-7-clinical-summary?)>

<!ATTLIST m2-common-technical-document-summaries %att;

>

<!ELEMENT m2-2-introduction ((leaf | node-extension)*)>

<!ATTLIST m2-2-introduction %att;

>

<!ELEMENT m2-3-quality-overall-summary (leaf*, m2-3-introduction?, m2-3-s-drug-substance*, m2-3-p-drug-product*, m2-3-a-appendices?, m2-3-r-regional-information?)>

<!ATTLIST m2-3-quality-overall-summary %att;

>

<!ELEMENT m2-3-introduction ((leaf | node-extension)*)>

<!ATTLIST m2-3-introduction %att;

>

<!ELEMENT m2-3-s-drug-substance ((leaf | node-extension)*)>

<!ATTLIST m2-3-s-drug-substance %att;

substance CDATA #REQUIRED manufacturer CDATA #REQUIRED

>

<!ELEMENT m2-3-p-drug-product ((leaf | node-extension)*)>

<!ATTLIST m2-3-p-drug-product %att;

product-name CDATA #IMPLIED dosageform CDATA #IMPLIED manufacturer CDATA #IMPLIED

>

<!ELEMENT m2-3-a-appendices ((leaf | node-extension)*)>

<!ATTLIST m2-3-a-appendices %att;

>

<!ELEMENT m2-3-r-regional-information ((leaf | node-extension)*)>

<!ATTLIST m2-3-r-regional-information %att;

>

<!ELEMENT m2-4-nonclinical-overview ((leaf | node-extension)*)>

<!ATTLIST m2-4-nonclinical-overview %att;

>

<!ELEMENT m2-5-clinical-overview ((leaf | node-extension)*)>

<!ATTLIST m2-5-clinical-overview %att;

>

<!ELEMENT m2-6-nonclinical-written-and-tabulated-summaries (leaf*, m2-6-1-introduction?, m2-6-2-pharmacology-written-summary?, m2-6-3-pharmacology-tabulated-summary?, m2-6-4-pharmacokinetics-m2-6-2-pharmacology-written-summary?, m2-6-5-pharmacokinetics-tabulated-summary?, m2-6-6-toxicology-written-summary?,

m2-6-7-toxicology-tabulated-summary?)>

<!ATTLIST m2-6-nonclinical-written-and-tabulated-summaries %att;

>

<!ELEMENT m2-6-1-introduction ((leaf | node-extension)*)>

<!ATTLIST m2-6-1-introduction %att;

>

<!ELEMENT m2-6-2-pharmacology-written-summary ((leaf | node-extension)*)>

<!ATTLIST m2-6-2-pharmacology-written-summary %att;

>

<!ELEMENT m2-6-3-pharmacology-tabulated-summary ((leaf | node-extension)*)>

<!ATTLIST m2-6-3-pharmacology-tabulated-summary %att;

>

<!ELEMENT m2-6-4-pharmacokinetics-written-summary ((leaf | node-extension)*)>

<!ATTLIST m2-6-4-pharmacokinetics-written-summary %att;

>

<!ELEMENT m2-6-5-pharmacokinetics-tabulated-summary ((leaf | node-extension)*)>

<!ATTLIST m2-6-5-pharmacokinetics-tabulated-summary %att;

>

<!ELEMENT m2-6-6-toxicology-written-summary ((leaf | node-extension)*)>

<!ATTLIST m2-6-6-toxicology-written-summary %att;

>

<!ELEMENT m2-6-7-toxicology-tabulated-summary ((leaf | node-extension)*)>

<!ATTLIST m2-6-7-toxicology-tabulated-summary %att;

>

<!ELEMENT m2-7-clinical-summary (leaf*, m2-7-1-summary-of-biopharmaceutic-studies-and-associated-analytical-methods?, m2-7-2-summary-of-clinical-pharmacology-studies?, m2-7-3-summary-of-clinical-efficacy*, m2-7-4-summary-of-clinical-safety?, m2-7-5-literature-references?, m2-7-6-synopses-of-individual-studies?)>

<!ATTLIST m2-7-clinical-summary %att;

>

<!ELEMENT m2-7-1-summary-of-biopharmaceutic-studies-and-associated-analytical-methods ((leaf | node-extension)*)>

<!ATTLIST m2-7-1-summary-of-biopharmaceutic-studies-and-associated-analytical-methods %att;

>

<!ELEMENT m2-7-2-summary-of-clinical-pharmacology-studies ((leaf | node-extension)*)>

<!ATTLIST m2-7-2-summary-of-clinical-pharmacology-studies %att;

>

<!ELEMENT m2-7-3-summary-of-clinical-efficacy ((leaf | node-extension)*)>

<!ATTLIST m2-7-3-summary-of-clinical-efficacy %att;

indication CDATA #REQUIRED

>

<!ELEMENT m2-7-4-summary-of-clinical-safety ((leaf | node-extension)*)>

<!ATTLIST m2-7-4-summary-of-clinical-safety %att;

>

<!ELEMENT m2-7-5-literature-references ((leaf | node-extension)*)>

<!ATTLIST m2-7-5-literature-references %att;

>

<!ELEMENT m2-7-6-synopses-of-individual-studies ((leaf | node-extension)*)>

<!ATTLIST m2-7-6-synopses-of-individual-studies %att;

>

<!ELEMENT m3-quality (leaf*, m3-2-body-of-data?, m3-3-literature-references?)>

<!ATTLIST m3-quality %att;

>

<!ELEMENT m3-2-body-of-data (leaf*, m3-2-s-drug-substance*, m3-2-p-drug-product*, m3-2-a-appendices?, m3-2-r-regional-information?)>

<!ATTLIST m3-2-body-of-data %att;

<!ELEMENT m3-2-s-drug-substance (leaf*, m3-2-s-1-general-information?, m3-2-s-2-manufacture?, m3-2-s-3-characterisation?, m3-2-s-4-control-of-drug-substance?, m3-2-s-5-reference-standards-or-materials?, m3-2-s-6-container-closure-system?, m3-2-s-7-stability?)>

<!ATTLIST m3-2-s-drug-substance %att;

substance CDATA #REQUIRED manufacturer CDATA #REQUIRED

>

<!ELEMENT m3-2-s-1-general-information (leaf*, m3-2-s-1-1-nomenclature?, m3-2-s-1-2-structure?, m3-2-s-1-3-general-properties?)>

<!ATTLIST m3-2-s-1-general-information %att;

>

<!ELEMENT m3-2-s-1-1-nomenclature ((leaf | node-extension)*)>

<!ATTLIST m3-2-s-1-1-nomenclature %att;

>

<!ELEMENT m3-2-s-1-2-structure ((leaf | node-extension)*)>

<!ATTLIST m3-2-s-1-2-structure %att;

>

<!ELEMENT m3-2-s-1-3-general-properties ((leaf | node-extension)*)>

<!ATTLIST m3-2-s-1-3-general-properties %att;

>

<!ELEMENT m3-2-s-2-manufacture (leaf*, m3-2-s-2-1-manufacturer?, m3-2-s-2-2-description-of-manufacturing-process-and-process-controls?, m3-2-s-2-3-control-of-materials?,

m3-2-s-2-4-controls-of-critical-steps-and-intermediates?, m3-2-s-2-5-process-validation-and-or-evaluation?, m3-2-s-2-6-manufacturing-process-development?)>

<!ATTLIST m3-2-s-2-manufacture %att;

>

<!ELEMENT m3-2-s-2-1-manufacturer ((leaf | node-extension)*)>

<!ATTLIST m3-2-s-2-1-manufacturer %att;

>

<!ELEMENT m3-2-s-2-2-description-of-manufacturing-process-and-process-controls ((leaf | node-extension)*)>

<!ATTLIST m3-2-s-2-2-description-of-manufacturing-process-and-process-controls %att;

>

<!ELEMENT m3-2-s-2-3-control-of-materials ((leaf | node-extension)*)>

<!ATTLIST m3-2-s-2-3-control-of-materials %att;

>

<!ELEMENT m3-2-s-2-4-controls-of-critical-steps-and-intermediates ((leaf | node-extension)*)>

<!ATTLIST m3-2-s-2-4-controls-of-critical-steps-and-intermediates %att;

>

<!ELEMENT m3-2-s-2-5-process-validation-and-or-evaluation ((leaf | node-extension)*)>

<!ATTLIST m3-2-s-2-5-process-validation-and-or-evaluation %att;

>

<!ELEMENT m3-2-s-2-6-manufacturing-process-development ((leaf | node-extension)*)>

<!ATTLIST m3-2-s-2-6-manufacturing-process-development %att;

>

<!ELEMENT 3-characterisation (leaf*, 3-1-elucidation-of-structure-and-other-characteristics?, m3-2-s-3-2-impurities?)>

<!ATTLIST m3-2-s-3-characterisation %att;

>

<!ELEMENT m3-2-s-3-1-elucidation-of-structure-and-other-characteristics ((leaf | node-extension)*)>

<!ATTLIST m3-2-s-3-1-elucidation-of-structure-and-other-characteristics

%att;

>

<!ELEMENT m3-2-s-3-2-impurities ((leaf | node-extension)*)>

<!ATTLIST m3-2-s-3-2-impurities %att;

>

<!ELEMENT m3-2-s-4-control-of-drug-substance (leaf*, m3-2-s-4-1-specification?,

m3-2-s-4-2-analytical-procedures?, m3-2-s-4-3-validation-of-analytical-m3-2-s-4-2-analytical-procedures?, m3-2-s-4-4-batch-analyses?, m3-2-s-4-5-justification-of-specification?)>

<!ATTLIST m3-2-s-4-control-of-drug-substance %att;

>

<!ELEMENT m3-2-s-4-1-specification ((leaf | node-extension)*)>

<!ATTLIST m3-2-s-4-1-specification %att;

>

<!ELEMENT m3-2-s-4-2-analytical-procedures ((leaf | node-extension)*)>

<!ATTLIST m3-2-s-4-2-analytical-procedures %att;

>

<!ELEMENT m3-2-s-4-3-validation-of-analytical-procedures ((leaf | node-extension)*)>

<!ATTLIST m3-2-s-4-3-validation-of-analytical-procedures %att;

>

<!ELEMENT m3-2-s-4-4-batch-analyses ((leaf | node-extension)*)>

<!ATTLIST m3-2-s-4-4-batch-analyses %att;

>

<!ELEMENT m3-2-s-4-5-justification-of-specification ((leaf | node-extension)*)>

<!ATTLIST m3-2-s-4-5-justification-of-specification %att;

>

<!ELEMENT m3-2-s-5-reference-standards-or-materials ((leaf | node-extension)*)>

<!ATTLIST m3-2-s-5-reference-standards-or-materials %att;

>

<!ELEMENT m3-2-s-6-container-closure-system ((leaf | node-extension)*)>

<!ATTLIST m3-2-s-6-container-closure-system %att;

>

<!ELEMENT m3-2-s-7-stability (leaf*, m3-2-s-7-1-stability-summary-and-conclusions?, m3-2-s-7-2-post-approval-stability-protocol-and-stability-commitment?, m3-2-s-7-3-stability-data?)>

<!ATTLIST m3-2-s-7-stability %att;

>

<!ELEMENT m3-2-s-7-1-stability-summary-and-conclusions ((leaf | node-extension)*)>

<!ATTLIST m3-2-s-7-1-stability-summary-and-conclusions %att;

>

<!ELEMENT m3-2-s-7-2-post-approval-stability-protocol-and-stability-commitment ((leaf | node-extension)*)>

<!ATTLIST m3-2-s-7-2-post-approval-stability-protocol-and-stability-commitment %att;

>

<!ELEMENT m3-2-s-7-3-stability-data ((leaf | node-extension)*)>

<!ATTLIST m3-2-s-7-3-stability-data %att;

>

<!ELEMENT m3-2-p-drug-product (leaf*, m3-2-p-1-description-and-composition-of-the-drug-product?, m3-2-p-2-pharmaceutical-development?, m3-2-p-3-manufacture?, m3-2-p-4-control-of-excipients*, m3-2-p-5-control-of-drug-product?, m3-2-p-6-reference-standards-or-materials?, m3-2-p-7-container-closure-system?, m3-2-p-8-stability?)>

<!ATTLIST m3-2-p-drug-product

product-name CDATA #IMPLIED dosageform CDATA #IMPLIED manufacturer CDATA #IMPLIED

>

<!ELEMENT m3-2-p-1-description-and-composition-of-the-drug-product ((leaf | node-extension)*)>

<!ATTLIST m3-2-p-1-description-and-composition-of-the-drug-product %att;

>

<!ELEMENT m3-2-p-2-pharmaceutical-development ((leaf | node-extension)*)>

<!ATTLIST m3-2-p-2-pharmaceutical-development %att;

>

<!ELEMENT m3-2-p-3-manufacture (leaf*, m3-2-p-3-1-manufacturers?, m3-2-p-3-2-batch-formula?, m3-2-p-3-3-description-of-manufacturing-process-and-process-controls?, m3-2-p-3-4-controls-of-critical-steps-and-intermediates?, m3-2-p-3-5-process-validation-and-or-evaluation?)>

<!ATTLIST m3-2-p-3-manufacture %att;

>

<!ELEMENT m3-2-p-3-1-manufacturers ((leaf | node-extension)*)>

<!ATTLIST m3-2-p-3-1-manufacturers %att;

>

<!ELEMENT m3-2-p-3-2-batch-formula ((leaf | node-extension)*)>

<!ATTLIST m3-2-p-3-2-batch-formula %att;

>

<!ELEMENT m3-2-p-3-3-description-of-manufacturing-process-and-process-controls ((leaf | node-extension)*)>

<!ATTLIST m3-2-p-3-3-description-of-manufacturing-process-and-process-controls %att;

>

<!ELEMENT m3-2-p-3-4-controls-of-critical-steps-and-intermediates ((leaf | node-extension)*)>

<!ATTLIST m3-2-p-3-4-controls-of-critical-steps-and-intermediates %att;

>

<!ELEMENT m3-2-p-3-5-process-validation-and-or-evaluation ((leaf | node-extension)*)>

<!ATTLIST m3-2-p-3-5-process-validation-and-or-evaluation %att;

>

<!ELEMENT m3-2-p-4-control-of-excipients (leaf*, m3-2-p-4-1-specifications?, m3-2-p-4-2-analytical-procedures?, m3-2-p-4-3-validation-of-analytical-procedures?, m3-2-p-4-4-justification-of-specifications?, m3-2-p-4-5-excipients-of-human-or-animal-origin?, m3-2-p-4-6-novel-excipients?)>

<!ATTLIST m3-2-p-4-control-of-excipients %att;

excipient CDATA #IMPLIED

>

<!ELEMENT m3-2-p-4-1-specifications ((leaf | node-extension)*)>

<!ATTLIST m3-2-p-4-1-specifications %att;

>

<!ELEMENT m3-2-p-4-2-analytical-procedures ((leaf | node-extension)*)>

<!ATTLIST m3-2-p-4-2-analytical-procedures %att;

>

<!ELEMENT m3-2-p-4-3-validation-of-analytical-procedures ((leaf | node-extension)*)>

<!ATTLIST m3-2-p-4-3-validation-of-analytical-procedures %att;

>

<!ELEMENT m3-2-p-4-4-justification-of-specifications ((leaf | node-extension)*)>

<!ATTLIST m3-2-p-4-4-justification-of-specifications %att;

>

<!ELEMENT m3-2-p-4-5-excipients-of-human-or-animal-origin ((leaf | node-extension)*)>

<!ATTLIST m3-2-p-4-5-excipients-of-human-or-animal-origin %att;

>

<!ELEMENT m3-2-p-4-6-novel-excipients ((leaf | node-extension)*)>

<!ATTLIST m3-2-p-4-6-novel-excipients %att;

>

<!ELEMENT m3-2-p-5-control-of-drug-product (leaf*, m3-2-p-5-1-specifications?, m3-2-p-5-2-analytical-procedures?, m3-2-p-5-3-validation-of-analytical-m3-2-p-5-2-analytical-procedures?, m3-2-p-5-4-batch-analyses?, m3-2-p-5-5-characterisation-of-impurities?, m3-2-p-5-6-justification-of-specifications?)>

<!ATTLIST m3-2-p-5-control-of-drug-product %att;

>

<!ELEMENT m3-2-p-5-1-specifications ((leaf | node-extension)*)>

<!ATTLIST m3-2-p-5-1-specifications %att;

>

<!ELEMENT m3-2-p-5-2-analytical-procedures ((leaf | node-extension)*)>

<!ATTLIST m3-2-p-5-2-analytical-procedures %att;

>

<!ELEMENT m3-2-p-5-3-validation-of-analytical-procedures ((leaf | node-extension)*)>

<!ATTLIST m3-2-p-5-3-validation-of-analytical-procedures %att;

>

<!ELEMENT m3-2-p-5-4-batch-analyses ((leaf | node-extension)*)>

<!ATTLIST m3-2-p-5-4-batch-analyses %att;

>

<!ELEMENT m3-2-p-5-5-characterisation-of-impurities ((leaf | node-extension)*)>

<!ATTLIST m3-2-p-5-5-characterisation-of-impurities %att;

>

<!ELEMENT m3-2-p-5-6-justification-of-specifications ((leaf | node-extension)*)>

<!ATTLIST m3-2-p-5-6-justification-of-specifications %att;

>

<!ELEMENT m3-2-p-6-reference-standards-or-materials ((leaf | node-extension)*)>

<!ATTLIST m3-2-p-6-reference-standards-or-materials %att;

>

<!ELEMENT m3-2-p-7-container-closure-system ((leaf | node-extension)*)>

<!ATTLIST m3-2-p-7-container-closure-system %att;

>

<!ELEMENT m3-2-p-8-stability (leaf*, m3-2-p-8-1-stability-summary-and-conclusion?, m3-2-p-8-2-post-approval-stability-protocol-and-stability-commitment?, m3-2-p-8-3-stability-data?)>

<!ATTLIST m3-2-p-8-stability %att;

>

<!ELEMENT m3-2-p-8-1-stability-summary-and-conclusion ((leaf | node-extension)*)>

<!ATTLIST m3-2-p-8-1-stability-summary-and-conclusion %att;

>

<!ELEMENT m3-2-p-8-2-post-approval-stability-protocol-and-stability-commitment ((leaf | node-extension)*)>

<!ATTLIST m3-2-p-8-2-post-approval-stability-protocol-and-stability-commitment %att;

>

<!ELEMENT m3-2-p-8-3-stability-data ((leaf | node-extension)*)>

<!ATTLIST m3-2-p-8-3-stability-data %att;

<!ELEMENT m3-2-a-appendices (leaf*, m3-2-a-1-facilities-and-equipment*, m3-2-a-2-adventitious-agents-safety-evaluation*, m3-2-a-3-excipients?)>

<!ATTLIST m3-2-a-appendices %att;

>

<!ELEMENT m3-2-a-1-facilities-and-equipment ((leaf | node-extension)*)>

<!ATTLIST m3-2-a-1-facilities-and-equipment %att;

manufacturer CDATA #IMPLIED substance CDATA #IMPLIED dosageform CDATA #IMPLIED product-name CDATA #IMPLIED

>

<!ELEMENT m3-2-a-2-adventitious-agents-safety-evaluation ((leaf | node-extension)*)>

<!ATTLIST m3-2-a-2-adventitious-agents-safety-evaluation %att;

manufacturer CDATA #IMPLIED substance CDATA #IMPLIED dosageform CDATA #IMPLIED product-name CDATA #IMPLIED

>

<!ELEMENT m3-2-a-3-excipients ((leaf | node-extension)*)>

<!ATTLIST m3-2-a-3-excipients %att;

>

<!ELEMENT m3-2-r-regional-information ((leaf | node-extension)*)>

<!ATTLIST m3-2-r-regional-information %att;

>

<!ELEMENT m3-3-literature-references ((leaf | node-extension)*)>

<!ATTLIST m3-3-literature-references %att;

>

<!ELEMENT m4-nonclinical-study-reports (leaf*, m4-2-study-reports?, m4-3-literature-references?)>

<!ATTLIST m4-nonclinical-study-reports %att;

>

<!ELEMENT m4-2-study-reports (leaf*, m4-2-1-pharmacology?, m4-2-2-pharmacokinetics?, m4-2-3-toxicology?)>

<!ATTLIST m4-2-study-reports %att;

>

<!ELEMENT m4-2-1-pharmacology (leaf*, m4-2-1-1-primary-pharmacodynamics?, m4-2-1-2-secondary-pharmacodynamics?, m4-2-1-3-safety-pharmacology?, m4-2-1-4-pharmacodynamic-drug-interactions?)>

<!ATTLIST m4-2-1-pharmacology %att;

>

<!ELEMENT m4-2-1-1-primary-pharmacodynamics ((leaf | node-extension)*)>

<!ATTLIST m4-2-1-1-primary-pharmacodynamics %att;

>

<!ELEMENT m4-2-1-2-secondary-pharmacodynamics ((leaf | node-extension)*)>

<!ATTLIST m4-2-1-2-secondary-pharmacodynamics %att;

>

<!ELEMENT m4-2-1-3-safety-pharmacology ((leaf | node-extension)*)>

<!ATTLIST m4-2-1-3-safety-pharmacology %att;

>

<!ELEMENT m4-2-1-4-pharmacodynamic-drug-interactions ((leaf | node-extension)*)>

<!ATTLIST m4-2-1-4-pharmacodynamic-drug-interactions %att;

>

<!ELEMENT m4-2-2-pharmacokinetics (leaf*, m4-2-2-1-analytical-methods-and-validation-reports?, m4-2-2-2-absorption?, m4-2-2-3-distribution?, m4-2-2-4-metabolism?, m4-2-2-5-excretion?, m4-2-2-6-pharmacokinetic-drug-interactions?, m4-2-2-7-other-pharmacokinetic-studies?)>

<!ATTLIST m4-2-2-pharmacokinetics %att;

>

<!ELEMENT m4-2-2-1-analytical-methods-and-validation-reports ((leaf | node-extension)*)>

<!ATTLIST m4-2-2-1-analytical-methods-and-validation-reports %att;

>

<!ELEMENT m4-2-2-2-absorption ((leaf | node-extension)*)>

<!ATTLIST m4-2-2-2-absorption %att;

>

<!ELEMENT m4-2-2-3-distribution ((leaf | node-extension)*)>

<!ATTLIST m4-2-2-3-distribution %att;

>

<!ELEMENT m4-2-2-4-metabolism ((leaf | node-extension)*)>

<!ATTLIST m4-2-2-4-metabolism %att;

>

<!ELEMENT m4-2-2-5-excretion ((leaf | node-extension)*)>

<!ATTLIST m4-2-2-5-excretion %att;

>

<!ELEMENT m4-2-2-6-pharmacokinetic-drug-interactions ((leaf | node-extension)*)>

<!ATTLIST m4-2-2-6-pharmacokinetic-drug-interactions %att;

>

<!ELEMENT m4-2-2-7-other-pharmacokinetic-studies ((leaf | node-extension)*)>

<!ATTLIST m4-2-2-7-other-pharmacokinetic-studies %att;

>

<!ELEMENT m4-2-3-toxicology (leaf*, m4-2-3-1-single-dose-toxicity?, m4-2-3-2-repeat-dose-toxicity?, m4-2-3-3-genotoxicity?, m4-2-3-4-carcinogenicity?, m4-2-3-5-reproductive-and-developmental-toxicity?, m4-2-3-6-local-tolerance?, m4-2-3-7-other-toxicity-studies?)>

<!ATTLIST m4-2-3-toxicology %att;

>

<!ELEMENT m4-2-3-1-single-dose-toxicity ((leaf | node-extension)*)>

<!ATTLIST m4-2-3-1-single-dose-toxicity %att;

>

<!ELEMENT m4-2-3-2-repeat-dose-toxicity ((leaf | node-extension)*)>

<!ATTLIST m4-2-3-2-repeat-dose-toxicity %att;

>

<!ELEMENT m4-2-3-3-genotoxicity (leaf*, m4-2-3-3-1-in-vitro?, m4-2-3-3-2-in-vivo?)>

<!ATTLIST m4-2-3-3-genotoxicity %att;

>

<!ELEMENT m4-2-3-3-1-in-vitro ((leaf | node-extension)*)>

<!ATTLIST m4-2-3-3-1-in-vitro %att;

>

<!ELEMENT m4-2-3-3-2-in-vivo ((leaf | node-extension)*)>

<!ATTLIST m4-2-3-3-2-in-vivo %att;

>

<!ELEMENT m4-2-3-4-carcinogenicity (leaf*, m4-2-3-4-1-long-term-studies?,

m4-2-3-4-2-short-or-medium-term-<!ATTLIST m4-2-3-4-carcinogenicity %att;

>

<!ELEMENT m4-2-3-4-1-long-term-studies ((leaf | node-extension)*)>

<!ATTLIST m4-2-3-4-1-long-term-studies %att;

>

<!ELEMENT m4-2-3-4-2-short-or-medium-term-studies ((leaf | node-extension)*)>

<!ATTLIST m4-2-3-4-2-short-or-medium-term-studies %att;

>

<!ELEMENT m4-2-3-4-3-other-studies ((leaf | node-extension)*)>

<!ATTLIST m4-2-3-4-3-other-studies %att;

>

<!ELEMENT m4-2-3-5-reproductive-and-developmental-toxicity (leaf*, m4-2-3-5-1-fertility-and-early-embryonic-development?, m4-2-3-5-2-embryo-fetal-m4-2-3-5-1-fertility-and-early-embryonic-development?, m4-2-3-5-3-prenatal-and-postnatal-development-including-maternal-function?, m4-2-3-5-4-studies-in-which-the-offspring-juvenile-animals-are-dosed-and-or-further-evaluated?)>

<!ATTLIST m4-2-3-5-reproductive-and-developmental-toxicity %att;

>

<!ELEMENT m4-2-3-5-1-fertility-and-early-embryonic-development ((leaf | node-extension)*)>

<!ATTLIST m4-2-3-5-1-fertility-and-early-embryonic-development %att;

>

<!ELEMENT m4-2-3-5-2-embryo-fetal-development ((leaf | node-extension)*)>

<!ATTLIST m4-2-3-5-2-embryo-fetal-development %att;

>

<!ELEMENT m4-2-3-5-3-prenatal-and-postnatal-development-including-maternal-function ((leaf | node-extension)*)>

<!ATTLIST m4-2-3-5-3-prenatal-and-postnatal-development-including-maternal-function %att;

>

<!ELEMENT m4-2-3-5-4-studies-in-which-the-offspring-juvenile-animals-are-dosed-and-or-further-evaluated ((leaf | node-extension)*)>

<!ATTLIST m4-2-3-5-4-studies-in-which-the-offspring-juvenile-animals-are-dosed-and-or-further-evaluated %att;

>

<!ELEMENT m4-2-3-6-local-tolerance ((leaf | node-extension)*)>

<!ATTLIST m4-2-3-6-local-tolerance %att;

>

<!ELEMENT 7-other-toxicity-studies (leaf*, 7-1-antigenicity?, 7-2-immunotoxicity?, m4-2-3-7-3-mechanistic-studies?, m4-2-3-7-4-dependence?, m4-2-3-7-5-metabolites?, m4-2-3-7-6-impurities?, m4-2-3-7-7-other?)>

<!ATTLIST m4-2-3-7-other-toxicity-studies %att;

>

<!ELEMENT m4-2-3-7-1-antigenicity ((leaf | node-extension)*)>

<!ATTLIST m4-2-3-7-1-antigenicity %att;

>

<!ELEMENT m4-2-3-7-2-immunotoxicity ((leaf | node-extension)*)>

<!ATTLIST m4-2-3-7-2-immunotoxicity %att;

>

<!ELEMENT m4-2-3-7-3-mechanistic-studies ((leaf | node-extension)*)>

<!ATTLIST m4-2-3-7-3-mechanistic-studies %att;

>

<!ELEMENT m4-2-3-7-4-dependence ((leaf | node-extension)*)>

<!ATTLIST m4-2-3-7-4-dependence

%att;

>

<!ELEMENT m4-2-3-7-5-metabolites ((leaf | node-extension)*)>

<!ATTLIST m4-2-3-7-5-metabolites %att;

>

<!ELEMENT m4-2-3-7-6-impurities ((leaf | node-extension)*)>

<!ATTLIST m4-2-3-7-6-impurities %att;

>

<!ELEMENT m4-2-3-7-7-other ((leaf | node-extension)*)>

<!ATTLIST m4-2-3-7-7-other %att;

>

<!ELEMENT m4-3-literature-references ((leaf | node-extension)*)>

<!ATTLIST m4-3-literature-references %att;

>

<!ELEMENT m5-clinical-study-reports (leaf*, m5-2-tabular-listing-of-all-clinical-studies?, m5-3-clinical-study-reports?, m5-4-literature-references?)>

<!ATTLIST m5-clinical-study-reports %att;

>

<!ELEMENT m5-2-tabular-listing-of-all-clinical-studies ((leaf | node-extension)*)>

<!ATTLIST m5-2-tabular-listing-of-all-clinical-studies %att;

>

<!ELEMENT m5-3-clinical-study-reports (leaf*, m5-3-1-reports-of-biopharmaceutic-studies?, m5-3-2-reports-of-studies-pertinent-to-pharmacokinetics-using-human-biomaterials?, m5-3-3-reports-of-human-pharmacokinetics-pk-studies?, m5-3-4-reports-of-human-pharmacodynamics-pd-m5-3-3-reports-of-human-pharmacokinetics-pk-studies?, m5-3-5-reports-of-efficacy-and-safety-studies*, m5-3-6-reports-of-postmarketing-experience?, m5-3-7-case-report-forms-and-individual-patient-listings?)>

<!ATTLIST m5-3-clinical-study-reports %att;

>

<!ELEMENT m5-3-1-reports-of-biopharmaceutic-studies (leaf*, m5-3-1-1-bioavailability-study-reports?, m5-3-1-2-comparative-ba-and-bioequivalence-study-reports?, m5-3-1-3-in-vitro-in-vivo-correlation-study-reports?, m5-3-1-4-reports-of-bioanalytical-and-analytical-methods-for-human-studies?)>

<!ATTLIST m5-3-1-reports-of-biopharmaceutic-studies %att;

>

<!ELEMENT m5-3-1-1-bioavailability-study-reports ((leaf | node-extension)*)>

<!ATTLIST m5-3-1-1-bioavailability-study-reports %att;

>

<!ELEMENT m5-3-1-2-comparative-ba-and-bioequivalence-study-reports ((leaf | node-extension)*)>

<!ATTLIST m5-3-1-2-comparative-ba-and-bioequivalence-study-reports %att;

>

<!ELEMENT m5-3-1-3-in-vitro-in-vivo-correlation-study-reports ((leaf | node-extension)*)>

<!ATTLIST m5-3-1-3-in-vitro-in-vivo-correlation-study-reports %att;

>

<!ELEMENT m5-3-1-4-reports-of-bioanalytical-and-analytical-methods-for-human-studies ((leaf | node-extension)*)>

<!ATTLIST m5-3-1-4-reports-of-bioanalytical-and-analytical-methods-for-human-studies %att;

>

<!ELEMENT m5-3-2-reports-of-studies-pertinent-to-pharmacokinetics-using-human-biomaterials (leaf*, 2-1-plasma-protein-binding-study-reports?, 2-2-reports-of-hepatic-metabolism-and-drug-interaction-studies?, m5-3-2-3-reports-of-studies-using-other-human-biomaterials?)>

<!ATTLIST m5-3-2-reports-of-studies-pertinent-to-pharmacokinetics-using-human-biomaterials %att;

<!ELEMENT m5-3-2-1-plasma-protein-binding-study-reports ((leaf | node-extension)*)>

<!ATTLIST m5-3-2-1-plasma-protein-binding-study-reports %att;

>

<!ELEMENT m5-3-2-2-reports-of-hepatic-metabolism-and-drug-interaction-studies ((leaf | node-extension)*)>

<!ATTLIST m5-3-2-2-reports-of-hepatic-metabolism-and-drug-interaction-studies %att;

>

<!ELEMENT m5-3-2-3-reports-of-studies-using-other-human-biomaterials ((leaf | node-extension)*)>

<!ATTLIST m5-3-2-3-reports-of-studies-using-other-human-biomaterials %att;

>

<!ELEMENT m5-3-3-reports-of-human-pharmacokinetics-pk-studies (leaf*, m5-3-3-1-healthy-subject-pk-and-initial-tolerability-study-reports?, m5-3-3-2-patient-pk-and-initial-m5-3-3-1-healthy-subject-pk-and-initial-tolerability-study-reports?, m5-3-3-3-intrinsic-factor-pk-study-reports?, m5-3-3-4-extrinsic-factor-pk-m5-3-3-3-intrinsic-factor-pk-study-reports?, m5-3-3-5-population-pk-study-reports?)>

<!ATTLIST m5-3-3-reports-of-human-pharmacokinetics-pk-studies %att;

>

<!ELEMENT m5-3-3-1-healthy-subject-pk-and-initial-tolerability-study-reports ((leaf | node-extension)*)>

<!ATTLIST m5-3-3-1-healthy-subject-pk-and-initial-tolerability-study-reports %att;

>

<!ELEMENT m5-3-3-2-patient-pk-and-initial-tolerability-study-reports ((leaf | node-extension)*)>

<!ATTLIST m5-3-3-2-patient-pk-and-initial-tolerability-study-reports %att;

>

<!ELEMENT m5-3-3-3-intrinsic-factor-pk-study-reports ((leaf | node-extension)*)>

<!ATTLIST m5-3-3-3-intrinsic-factor-pk-study-reports %att;

>

<!ELEMENT m5-3-3-4-extrinsic-factor-pk-study-reports ((leaf | node-extension)*)>

<!ATTLIST m5-3-3-4-extrinsic-factor-pk-study-reports %att;

>

<!ELEMENT m5-3-3-5-population-pk-study-reports ((leaf | node-extension)*)>

<!ATTLIST m5-3-3-5-population-pk-study-reports %att;

>

<!ELEMENT m5-3-4-reports-of-human-pharmacodynamics-pd-studies (leaf*, m5-3-4-1-healthy-subject-pd-and-pk-pd-study-reports?, m5-3-4-2-patient-pd-and-pk-pd-study-reports?)>

<!ATTLIST m5-3-4-reports-of-human-pharmacodynamics-pd-studies %att;

>

<!ELEMENT m5-3-4-1-healthy-subject-pd-and-pk-pd-study-reports ((leaf | node-extension)*)>

<!ATTLIST m5-3-4-1-healthy-subject-pd-and-pk-pd-study-reports

<!ATTLIST m5-3-4-1-healthy-subject-pd-and-pk-pd-study-reports

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