material traceability from api to patient · 2012-10-24 · 6 material traceability and materials...
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![Page 1: Material Traceability from API to Patient · 2012-10-24 · 6 Material Traceability and Materials Management Batch vs. Continuous Processing* • Multiple batches of API and/or excipients](https://reader034.vdocuments.net/reader034/viewer/2022042802/5f3e852b6f7456301f7ed14b/html5/thumbnails/1.jpg)
1 ©2012 Vertex Pharmaceuticals Incorporated
Material Traceability from API to Patient -Current State, Near Term Changes and Future Possibilities Using Continuous Processing Data
Kyle Kelley, Vice President Supply Chain Management
IFPAC Conference | October 2012
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Material Traceability from API to Patient
• Review Vertex's proposed initial approach to continuous processing material traceability.
• Overview of industry traceability challenges from manufacturing plants to patient and Vertex's approach to comply with upcoming track and trace regulations.
• A possible step-wise process to provide an even greater degree of traceability by utilizing continuous processing product key information will be presented.
©2012 Vertex Pharmaceuticals Incorporated2
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Confidential Vertex Pharmaceuticals Incorporated3
Continuous Manufacturing
• Powder in, coated tablets out
Much smaller footprint
Continuous monitoring “Real Time Release”
Powder In
Coated Tablets Out
• Smaller-scale equipment• All unit ops in one suite
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Key Concepts Related to Traceability Using Continuous Processing - Product Keys
©2012 Vertex Pharmaceuticals Incorporated
Smallest traceable unit of production– ~3 min of production– Corresponds to 0.5 to 1.5 kg of
product– Very well characterized
• Input materials• Process parameters• IPCs and end product testing
Machine designed to minimize inter-mixing between PKsCommercial “batch” comprises multiple PKs
– e.g. 500 PKs 625kg batch at 25kg/hr production rate
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©2011 Vertex Pharmaceuticals Incorporated5
Batch and Bill of Materials Definition using Continuous Processing
Excipient A - Lot 2
x kgs of Excipient B - Lot 1
API- Lot 2
x kg of Excipient A - Lot 1
X kgs of API - Lot 1
nini ni ni ni nZ ni ni ni ni nin3 ni nin1 n2 ni
………
Batch N1 Batch N2
…
…T
API- Lot 3
y kg
y kg
Batches Defined Batches defined within a design space established for manufacturing time and rate
Example - BOM for Batch N1:•From n1 – nZ (PKs) from 0 - T•Excipient A (x Kgs Lot 1 and y kgs Lot 2])•Excipient B (k kgs Lot 1)•API (x Kgs Lot 1 + y kgs Lot 2])
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Material Traceability and Materials Management Batch vs. Continuous Processing*
• Multiple batches of API and/or excipients may be used in the same batch of drug product.
• Following batch release each drum of material from a given batch will be of UNIFORM quality
• can be used interchangeably with other drums from the same batch• lot geneaology maintained at batch level (not container) level.
Batch ProcessingBatch Processing Continuous Processing*Continuous Processing*
• Bill of Materials (BOM) generated PRIORto manufacture.
• API and excipients blended beforemanufacture.
• Batch typically of uniform size (less samples/segregated material)
• Unit Operations for each batch typically take several weeks from start to finish
• Final Bill of Materials generated POSTmanufacture.
• API and excipients NOT blended before manufacture.
• Batch size may vary depending manufacturing rate and time (within pre-specified design space limits)
• Batches usually complete in limited period of time
Sim
ilarit
ies
Diff
eren
ces
©2012 Vertex Pharmaceuticals Incorporated6 Confidential Vertex Pharmaceuticals Incorporated
* Initial Continuous Processing materials management strategy. This may evolve over time
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Material Traceability API to Patient - Current State
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Company Distribution
CenterBulk Active Ingredient
Bulk Drug Product
Packaging & Labeling
POINT OF SALE
Wholesaler
Specialty Pharmacy
Retail
Patients
Deg
ree
of T
race
abili
ty
Batch /Lot Level Traceability required by cGMP on Usage and Shipments
Lot Level Traceability Typically Lost in Wholesale Channel
Lot Level Traceability Frequently (but not always) Maintained Thru
Pharmacy Channel
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Material Traceability API to Patient -Near Term 2013-2015
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Company Distribution
CenterBulk Active Ingredient
Bulk Drug Product
Packaging & Labeling
POINT OF SALE
Wholesaler
Specialty Pharmacy
Retail
Patients
Deg
ree
of T
race
abili
ty
Batch /Lot Level Traceability required by cGMP on Usage and Shipments
Individual Unit of Sale Authentication
Individual Unit of Sale Authentication and Pedigree Traceability
Authentication/Pedigree to be required by Law in Many Countries in 2015 timeframe
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Global Traceability InitiativesHigh Regulation / Complexity
Minimal Regulation / Complexity
Highly DefinedMinimally Defined
Turkey
Argentina
California
Columbia
India
France*
Italy
Greece
Spain
Japan
NetherlandsCanada
Brazil
ChinaEU
Transmission and Serialization
Transmission without Serialization
Serialization & Product Number Tracking
Product Number Tracking
•New Development: Transmission potentially outlined in a 2011 Press release
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Serial # Manager (S#M)
Event Repository
(ER)
Serialization and ePedigree - What’s involved?
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Push Serial # to Packager
Commissioning Info to S#M and Aggregation
info to ER Event Capture and EDI to ER
Serial # Query Routed to ER and Response Pushed Back
Serialization ePedigree Authentication
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©2012 Vertex Pharmaceuticals Incorporated11
2013 2014
ee
Additional product serializaiton effortsAdditional product serializaiton efforts
2014
ePedigree ImplementationePedigree Implementation
US ePedigree Regulations –
50% of product
2012 2013 2015
Serialization pilotSerialization pilot
Implement Serialization on at least 1 product
(Authentication)
Implement Serialization on at least 1 product
(Authentication)
Vertex’s Plan to improve Traceability of Unit Doses
Implement Line‐Level Serialization @ 1°Pack Site
Implement Line‐Level Serialization @ 1°Pack Site
Install /ValidateSerial # Manager +
EPCIS Event Repository
Install /ValidateSerial # Manager +
EPCIS Event Repository
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Stage 3~2015
Future Possibilities of Material Traceability Using CP Data -
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Stage 12013-4
Stage 2~2014
Continuous Processing
Implement technology and gain regulatory acceptance using
Define Possibilities of Individual (or Grouped) Product Key Level
Traceability
Implement Continuous Processing Bottle / Blister
Packaging Technology
Serialization / ePedigree Program
Implement Serialization and Unit of Sale Authentication Program
Implement Limited (Market and/or product specific ePedigree/ Track+Trace ) Program
Implement Broad ePedigree/ Track+Trace Program
Stage 42016+
One Global Traceability Program
Implement Serialized Packaging Lines on Continuous Processing Rigs and Trace Individual Units of Sale Using Global Track and Trace Program
TRACE PRODUCT KEY TO DISPENSE
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Traceability and recall examples
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Advantages and Challenges to Global Product Key to Dispense Traceability Program
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Key Advantages:•Patient Safety -
• Recalls can be very focused - time and efficiency saving• Tight control over supply chain - lower risk of counterfeit/diversion
•Product Key Traceability can lead to increased product understanding and increase overall product quality•Distribution Data can identify diversion/Counterfeit locations leading to increased enforcement
Key Challenges:•Product Key to Unit
• Technical and regulatory challenges in limiting and regulating the potential for intermixing of product keys
• Packaging for Continuous Processing still under development•Unit to Patient
• Proposed regulations for Authentication, Serialization, ePedigree vary significantly between regions - Harmonization NEEDED
• Technical challenges - read rates of RFID and other enabling technologies• Industry acceptance (especially downstream) will require much discussion.