# Presentation: 779876

## Introduction to SPL Changes with the Physician Labeling Rule

- Steven Gitterman
- Laurie Burke
- Randy Levin

- March 16, 2005
- Version 2

## Outline

- Brief overview of SPL
- Introduction to the Physicians Labeling Rule
- Relationship between the Physicians Labeling Rule and the SPL

## What is SPL

- A model-derived standard adopted for the exchange of FDA-regulated product information including:
- Content of labeling
- Coded information from the content of labeling (‘data elements’)
- Wrapper for electronic listing elements
- Required with drug submissions since 10/05

## SPL Release 1 (2a)

- Adopted by CDER for products as of October, 2005.
- Used to model *existing* labels
- Extremely (exceptionally!) flexible
- Constraints defined by FDA implementation guide (_[http://www.fda.gov/oc./datacouncil/spl.html](http://www.fda.gov/oc./datacouncil/spl.html)__)_

## An Old Example....

## XML Code Snippet

- <component>
- 	<section>
- 	<id root="f278d120-fded-11d8-ae89-15c8e06e3da2"/>
- 	<code code="34090-1" codeSystem="2.16.840.1.113883.6.1"  codeSystemName= "LOINC" displayName="CLINICAL PHARMACOLOGY SECTION"/>
- 	<title>CLINICAL PHARMACOLOGY</title>
- 	<component>
- 		<section>
- 			<id root="f278d121-fded-11d8-ae89-15c8e06e3da2"/>
- 			<code code="34067-9" codeSystem="2.16.840.1.113883.6.1" 					codeSystemName="LOINC"/>
- 			<title> Mechanism of Action</title>
- 			<text>
- 				<paragraph> The cysteinyl leukotrienes (LTC<sub>4</sub>, 			LTD<sub>4</sub>, LTE<sub>4</sub>) are products of 			arachidonic acid metabolism and are released from various cells, 		including mast cells and eosinophils. These eicosanoids bind to 			cysteinyl leukotriene (CysLT)

## Three Major Aspects to SPL Rel. 1

- Header
- Body
- Narrative (+ images)
- Tables
- ‘Data elements’ within body

## Physician Labeling Rule (PLR)

**The Physician Labeling Rule**
- FR Notice  Vol. 71, No. 15, 1/24/06
- Revises 21 CFR § 201.57
- Approved labeling now has 3 parts:
- Highlights
- Contents
- Full prescribing information (FPI)
- Identifies and Dates “Recent Major Changes”
- Captures *Indications, D&A, Boxed Warning, CI and W&P*
- Referenced in* Highlights*; margin mark in FPI
- Added date of initial US approval

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## Physician Labeling Rule

- Supporting information available at:
- _[http://www.fda.gov/cder/regulatory/physLabel/](http://www.fda.gov/cder/regulatory/physLabel/)_
- Supporting guidance:
- Labeling content and format (*draft*)
- Adverse Reactions (*final*)
- Clinical Studies (*final*)
- Warning and Precautions, Contraindications and Boxed Warning (*draft*)
- Fictitious labeling examples
- FAQs** **

## Format Innovations

- Reorders and reorganizes sections
- Establishes format requirements
*Warnings and Precautions* consolidated
- New sections
*Drug Interactions*
*Dosage Forms and Strengths*
*Use in Specific Populations*
*Patient Counseling Information*
- Formerly optional, now required
*Clinical Studies*
*Nonclinical Toxicology*

## Contents and Full Prescribing Information (FPI)

- Boxed Warning
- 1 Indications & Usage
- 2 Dosage & Administration
- 3 Dosage Forms & Strengths
- 4 Contraindications
- 5 Warnings & Precautions
- 6 Adverse Reactions
- 7 Drug Interactions
- 8 Use in Specific Populations*
- 9 Drug Abuse & Dependence*

- 10 Overdosage
- 11 Description
- 12 Clinical Pharmacology*
- 13 Nonclinical Toxicology*
- 14 Clinical Studies
- 15 References
- 16 How Supplied/Storage &      Handling
- 17 Patient Counseling Information
- * Indicates sections with specified numbering of subsections

## Sample Highlights Section

## SPL and PLR

- What is new for SPL with the implementation of the PLR
- Recent major changes notation
- Highlights text
- Highlights data elements

## Recent Major Changes Notation

- New labeling information
- Recent major changes tagged in the labeling text using styleCode text tag
- <text>This is an example of text that is not changed.<content styleCode=“xmChange”>This is an example of text that is a recent major change</content>This is an example of changed text that is not considered a recent major change</text>

- *This slide has been changed since the presentation

## Highlights Text

- Text is provided for each section of the Highlights
- Sections with Highlights text
- Box Warning
- Recent Major Changes
- Indications and Usage
- Dosage and Administration
- Dosage Forms and Strengths
- Contraindications
- Warnings and Precautions
- Adverse Reactions
- Drug Interactions
- Use in Specific Populations
- Patient Counseling Information

## Highlights Text

## Highlights Text

- <excerpt>
- <highlight>
**<text></text>**
**<effectiveTime></effectiveTime>**
- </highlight>
- </excerpt>

## Highlights Data Elements

- Company and approval information
- Indications and usage
- Interactions and adverse reactions

## Company and Approval Information

- Company information
- Company Name
- Labeler code
- Phone number for reports
- Web address for reports
- Approval information
- Date of initial approval

## Document Level

**[Company information]**

**[Approval information]**

## Company Information

**[Company name]**

**[Labeler code]**

**[Contact info]**

## Approval Information

**[Initial approval]**

## <legalAuthenticator>
<time></time>
<assignedEntity>
<telecom>phone number here</telecom>
<telecom>web address here</telecom>
<representedOrganization>
	<id root=“2.16.840.1.113883.6.69” extension=“0001”/>
	<name>company name here</name>
	</representedOrganization>
</assignedEntity>
</legalAuthenticator>
<verifier>
	<time value="2005"/>
	<assignedEntity/>
</verifier>

- <time></time>
- <assignedEntity>
**<telecom>phone number here</telecom>**
**<telecom>web address here</telecom>**
- <representedOrganization>
- 	**<id root=“2.16.840.1.113883.6.69” extension=“0001”/>**
- 	<name>company name here</name>
- 	</representedOrganization>
- </assignedEntity>
- </legalAuthenticator>
- <verifier>
- 	**<time value="2005"/>**
- 	<assignedEntity/>
- </verifier>

- Company and Approval Information

- [Company name]

- [Labeler code]

- [Contact info]

- [Initial approval]

## Indications and Usage Data Elements

- Indication
- Highlights text
- Intent of use
- Indication code
- Usage
- Limitation of use
- Limitation of use category
- Precondition category
- Precondition
- Condition of use
- Adjunct therapy and Screening/monitoring
- Precondition category
- Precondition
- Maximum dose
- Amount per time period
- Pharmacological class

## Indications and Usage

**reason**

**subjectOf**

**precondition**

**componentOf**

**maxDoseQuantity**

## Indication

**[Intent of use]**

**[Indication category]**

**[Indication code]**

## Indication

- <reason typeCode=“xxxx">
- <indicationObservationCriterion>
- <code code=“44100-6" codeSystem="2.16.840.1.113883.6.1" displayName=“Medical Problem"/>
- <value code=“xxxx" codeSystem="2.16.840.1.113883.x.xx" displayName=“xxxx"/>
- </indicationObservationCriterion>
- </reason>

**[Indication category]**

**[Intent of use]**

**[Indication code]**

## Limitation of Use

**[Limitation of use category]**

**[Precondition category]**

**[Precondition]**

## Limitation of Use

- <subjectOf>
- <issue>
- <code code=“xxx" codeSystem="2.16.840.1.113883.3.26.1.1" displayName=“xxxx"/>
- <subject>
- <observationCriterion>
- <code code=“xxx" codeSystem="2.16.840.1.113883.6.1" displayName=“xxxx"/>
- <value xsi:type="CE" code=“xxx" codeSystem="2.16.840.1.113883.3.xx.x" displayName=“xxx"/>
- </observationCriterion>
- </subject>
- </issue>
- </subjectOf>

**[Limitation of use category]**

**[Precondition category]**

**[Precondition]**

## Condition of Use

**[Precondition category]**

**[Precondition]**

## Condition of Use

- <precondition>
- <observationCriterion>
- <code code="xxx" codeSystem="2.16.840.1.113883.6.1" displayName="xxx"/>
- <value xsi:type="CE" code="xxx" codeSystem="2.16.840.1.113883.3.xxx" displayName="xxx"/>
- </observationCriterion>
- </precondition>

**[Precondition category]**

**[Precondition]**

## Adjunct Treatment

## Adjunct Treatment

- <precondition>
- <substanceAdministrationCriterion>
- <consumable>
- <administrableMaterial>
- <playingMaterialKind>
-      <code code="xxx" codeSystem="2.16.840.1.113883.4.9" displayName=“xxx"/>
- </playingMaterialKind>
- </administrableMaterial>
- </consumable>
- </substanceAdministrationCriterion>
- </precondition>

**[Adjunct treatment]**

## Screening/Monitoring Test

**[Screening/monitoring test]**

## Screening/Monitoring Test

- <componentOf>
- <protocol>
- <component>
- <monitoringObservation>
- <code code="xxx" codeSystem="2.16.840.1.113883.6.1" displayName=“xxx"/>
- </monitoringObservation>
- </component>
- </protocol>
- </componentOf>

**[Screening/monitoring test]**

## Maximum Dose

## Maximum Dose

- <highlight>
- <subject>
- <substanceAdministration>
- <maxDoseQuantity>
- <numerator value=“xxx" unit=“xxx"/>
- <denominator value=“xxx" unit=“xxx"/>
- </maxDoseQuantity>
- </substanceAdministration>
- </subject>
- </highlight>

## Interactions and Adverse Reactions

- Highlights text
- Contributing factor*
- Type of consequence
- Consequence
- Pharmacological Class

- *Not applicable to Adverse Reactions

## Interactions and Adverse Reactions

**subjectOf**

**consumable**

## Contributing Factor

**[Contributing factor]**

## Contributing Factor

- <issue>
-    <subject>
- <substanceAdministrationCriterion>
- <consumable>
- <administrableMaterial>
- <playingMaterialKind>
-       <code code="xxx"
- codeSystem="xxx“
- displayName=“xxxx"/>
- </playingMaterialKind>
- </administrableMaterial>
- </consumable>
- </substanceAdministrationCriterion>
-    </subject>
- </issue>

**[Contributing factor]**

## Consequence

**[Type of consequence]**

**[Consequence]**

## Consequence

- <risk>
- <consequenceObservation>
- <code code= “xxxx"
- codeSystem="2.16.840.1.113883.3.26.1.1"
- displayName=“xxxx"/>
- <value xsi:type="CE"
- code= “xxxx"
- codeSystem="xxx"
- displayName=“xxxx"/>
- </consequenceObservation>
- </risk>

**[Type of consequence]**

**[Consequence]**

## Interaction and Adverse Reaction

- <excerpt>
- <highlight>
- <text></text>
- <effectiveTime></effectiveTime>
- <subject>
- <substanceAdministration>
- <subjectOf>
-      <issue>
-          <subject>
-               <substanceAdministrationCriterion></substanceAdministrationCriterion>
-          </subject>
-          <risk></risk>
-      </issue>
- </subjectOf>
- </substanceAdministration>
- </subject>
- </highlight>
- </excerpt>

**[Contributing factor]**

**[Consequence]**

**[Highlights text]**

**[Type of consequence]**

## Pharmacological Class

- Important for both indications and interactions
- Pharmacological Class defined by:
- Mechanism of action
- Physiologic effect
- Structural class
- Highlights data elements
- Pharmacological class data elements under ingredient or product

## Pharmacological Class

## Pharmacological Class by Ingredient

- <activeIngredient>
-   <activeIngredientSubstance>
-     <specializedKind>
-       <generalizedPharmaceuticalClass>
- 	<code code=“xxxx” codeSystem=“2.16.840.1.113883.3.26.1.5” displayName=“xxx”/>
-       </generalizedPharmaceuticalClass>
-     </specializedKind>
-   </activeIngredientSubstance>
- </activeIngredient>

## Pharmacological Class by Product

- <manufacturedMedicine>
- <specializedKind>
-       <generalizedPharmaceuticalClass>
- 	<code code=“xxx” codeSystem=“2.16.840.1.113883.3.26.1.5” displayName=“xxx”/>
-       </generalizedPharmaceuticalClass>
-     </specializedKind>
-   </manufacturedMedicine>

## Terminology

- NCI Thesaurus
- Limitation of use category
- Sex and race
- General contributing factors
- Pharmacokinetic effects
- Type of consequence
- LOINC
- Indication category
- Precondition category
- Lab tests

- FDA SRS and DRLS
- Foods and drugs
- Problem List Subset
- Indication code
- Medical problems
- HL7
- Intent of use
- NDF-RT
- Pharmacological class