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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
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
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
4
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
©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])
6
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
Material Traceability API to Patient - Current State
7
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
Material Traceability API to Patient -Near Term 2013-2015
8
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
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
Serial # Manager (S#M)
Event Repository
(ER)
Serialization and ePedigree - What’s involved?
10
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
©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
Stage 3~2015
Future Possibilities of Material Traceability Using CP Data -
12
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
Traceability and recall examples
13
Advantages and Challenges to Global Product Key to Dispense Traceability Program
14
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.