Building, Managing and Continuously Improving Clinical

Supply Chains

IQPC Clinical Trial Supply Europe, Basel, February 1 2012

Presented by:

Hedley Rees, Director

AGENDA

Where are we now in the Pharma supply chain?

What could the future hold?Case study: Perfect Pills and PotionsDiscussion

www.globalcompliancepanel.com 2

Where are we now in the Pharma supply chain?

The Supply Chain Fragments…. 1970's:

Prevailing business model vertical integration

local market management presence.

predominately small molecule manufactured by chemical synthesis.

1980’s

Outsource non-core activities

Manufacture, analytics, distribution, storage

Since

New business models - innovator, virtual, biotech, generic/bio-similars and speciality Pharma

Biologics form important portfolio position, with temperature and time sensitivities

Markets have globalised into new territories

Number and location of third party contractors and service providers proliferate.

A typical Pharma supply chain

Generic Supply-Chain- Material Flow -

APISupplier 4

TabletsSupplier 7

Finished Packs

Supplier 9

CTS &Storage

Supplier 11

Investigator Sites

APISupplier 5

CTS &Storage

Supplier 10

Marketing Partners

TabletsSupplier 8

Regional Depots

Starting Material ASupplier 2

Starting Material ASupplier 3

Starting Material BSupplier 4

Starting Material BSupplier 5

Starting Material BSupplier 6

Starting Material ASupplier 1

CTS LabelsSupplier 12

PackagingSupplier 13

BottlesSupplier 14

In-Place

Planned

Current state supply-chain

Information, information, information….

II

Oversee process development.

Contract Ops Manuals (COM)

Master Batch Record review.

Pharm OpsMPS model.

Boundary scenariosSupply agreementsRisk Assessments.

Supply Chain

Territory.Market responsibility (Co-

Prom?).Annual rolling fcorecast.

PO’sAnti-counterfeiting.

Trade dress definition.

PartnerChem Ops

Methods developmentMethods Transfer

Review of test results

Analytical

Master Validation Protocols

Batch record reviewMaterial disposition

Shelf life determination

QA

Oversee process development.

Contract Ops Manuals (COM)

Master Batch Record review.

Buy to spec.commercially available

Identity checkRelease testing

CofA’s

Starting Materials

Shelf life starting point.Hold time(s)Stability data

Drug Product

Shelf life/re-test

API

Registered shelf lifeNeed to store buffer inventory for partner

(x months)?

Packaged Product

Store product to GMP

Distribution Centre

Make print-ready artworkGNE/OSI approval

Compatible with packaging contractor

needs

Artwork Origination -Contact UK

Concept artwork

Print ready artwork

Updated monthly schedule (per

supply agreement)

II II II II

Hold starting materials & API

Real time inventoryTransfer order from

Supply Chain

Secure GMP Store

Need material specsSamples required

Flexibility to deal with changes

Packaging Printers - US

Inventory report

Monthly rolling

forecasts

Purchaseorder

Schedulesfor review

Artwork

Samples

Schedules

CofA

CofA

CofA

MBR creation

& approval

MBR creation

& approvalBatch record Batch record

Manufacturing schedule

Batch record

Request to ship

Material disposition status

Request to ship

CofACofA

MBR creation& approval

MBR creation

& approval

Batch record

Invoices

Inventoryreport

Supply chain foundations begin in drug development

Sponsor Company

How the supply chain is formed

Supplying Pre-Clinical Programs Sponsor

Company

Typical End-to-End Supply Chain – First in Humans Study

• Initial dosage form may be compromise eg hard gel capsule.

• Can disguise issues such as poor dissolution profile.

• Final dosage form may be compromise.• Initial inertia to change established.• Filing contains sub-optimal data.• Sourcing options limited by filing.• Locked-in to processes, contractors and other

Value Chain parameters.

Sponsor Company

• Initial dosage form may be compromise eg hard gel capsule.

• Can disguise issues such as poor dissolution profile.

• Final dosage form may be compromise.• Initial inertia to change established.• Filing contains sub-optimal data.• Sourcing options limited by filing.• Locked-in to processes, contractors and other

Value Chain parameters.

Examples of potential issues

12

Sponsor Company

Examples of potential issues

CostMaterial priceYield lossesBatch failuresRe-workAge-expiry

Quality100% inspectionInvestigationsCAPACustomer complaints

Delivery PerformanceLong lead timesStock-outsShortagesCustomer returns

What could the future hold?

The 21st Century Initiative

Pharmaceutical cGMP’s for the 21st Century – A Risk-Based Approach:

Started 2002 and reported late 2004Desired state:

“A maximally efficient, agile, flexible pharmaceutical manufacturing sector without extensive regulatory oversight.”

Dr. Janet Woodcock, the U.S. Food and Drug Administration's Deputy Commissioner for Operations

History of improvement in production systems

Industrial Engineering (IE)Total Quality Management (TQM)World Class Manufacturing (WCM)Theory of Constraints (ToC)Toyota Production System (TPS)Systems ThinkingDeming wrote the book over 50 years ago!

The Supply Chain Holistic

Production & Inventory Control (P&IC)ProcurementTransportation, storage and delivery Information Systems/Information Technology (IS/IT) Improvement Integration

Linking up the value chains

Lean background

NUMMI study, Womack & Jones “The Machine That Changed the World”

Based on Toyota Production System (TPS)Reduce time between getting order and money in

Respect for peopleContinuous improvement

Five principlesMany parallels with TQM, WCM, TOC, etc.

Five Principles of Lean

1. Specify value from the standpoint of the end customer by product family.

2. Identify all the steps in the value stream for each product family, eliminating whenever possible those steps that do not create value.

3. Make the value-creating steps occur in tight sequence so that the product will flow smoothly toward the customer.

4. As flow is introduced, let customers pull value from the next upstream activity.

5. As value is specified, value streams are identified, wasted steps are removed, and flow and pull are introduced, continue until a state of perfection is reached in which value is created with no waste.

Process Village v Value Stream

Traditional functional layout– solid dose

Key points:Large batchesProduce to forecastHigh in-process inventoryDefects are hidden

Value stream alignment – solid dose

Key points:Schedule pacemaker only.Set rate at TAKT (Production rate required to match rate of consumption in the market place.Pull from the pacemaker (Kanbans and supermarkets)Solve production problems (A3 Management)Take out variation (SPC).Reduce defect rates on incoming materials.Use Single Minute Exchange of Dies (SMED) to reduce cycle time

Case study: Perfect Pills and Potions

Discussion

Check list…

Identifying stakeholdersListening to Voice of the Customer (VoC)Defining Critical to Quality Attributes (CTQs)Creating 'one shared view'Analysing the current state mapSeeing the wholeDeciding architecture and reachAgreeing target and future statesDeveloping a control planGaining organisational buy-in

QuestionsIf there are any further questions which I was

not able to get to today please feel free to contact me at:

H.rees@pharmaflowltd.co.uk