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.