transforming technology transfer and recipe management: from spreadsheets to standardized practices
DESCRIPTION
Presented by Paul Wlodarczyk at Documentation and Training Life Sciences, June 23-26, 2008 in Indianapolis.The creation and management of formulation and control recipes is a process that is overdue for transformation. Today, most pharmaceutical companies still rely on error-prone, manual recipe-management approaches, in which master recipes are treated as static and disconnected documents. These outdated approaches lead to delays in technology transfer and introduce errors as formulations are entered into execution and quality management systems. Inefficient technology transfer, in turn, leads to delays in commercialization, waste or poor yield, compliance challenges, and risks to product quality.Recipe standardization and management can improve every aspect of the product lifecycle, from late-stage discovery through clinical and commercial manufacturing. As pharmaceutical companies increasingly implement Quality by Design principles, recipe standardization will ensure that critical process parameters and their ranges are documented in a uniform fashion, from the earliest phases of process development and then managed effectively through all stages of manufacturing.This slide deck explores new approaches for standardizing recipe management to mitigate risk and accelerate time to market. You will see case studies and be provided with a framework for understanding how to migrate to standards-based recipe-management practices.TRANSCRIPT
Dynamic Information Now for Everyone©2008 JustSystems
Transforming Technology Transfer Transforming Technology Transfer and Recipe Managementand Recipe Management
From Spreadsheets to Standardized PracticesFrom Spreadsheets to Standardized Practices
Paul Wlodarczyk, VP Solutions Consulting, JustSystems
DocTrain Life Sciences
24 June 2008
2Dynamic Information Now for Everyone©2008 JustSystems
Business Imperative: Top ThreeBusiness Imperative: Top ThreeLife Science Innovation Goals for 2012 Life Science Innovation Goals for 2012 1. Leverage scientific/ technological advances to assure superior
therapeutic outcomes in their target patient population.
2. Improve acquisitions/ alliance / licensing management processes to improve agility in bringing new products to market.
3. Decrease the concept-to-patient lifecycle from the current 7-11 years to 5-7 years
Survey respondents estimated 19% growth in spending on technology to support R&D in 2012; this is slightly higher among branded and generics with estimated growth of 23%. Mid-market Life Sciences companies also plan for more aggressive growth than their larger counterparts, they plan to increase their spending by nearly 30%.
Source: AMR Research 2007 Life Sciences Survey
ProductProduct
DemandDemand SupplySupply
3Dynamic Information Now for Everyone©2008 JustSystems
ProcessDefinition
Pilot Scale
Early Development Late Development
Project Management
LIMS / SDMS
QMS / CAPA
Lab Scale
ElectronicLab
Notebooks
Users
Project Operations
Scientists Chemists
BiologistsPharmacistsEngineers
TechniciansOperators
Support
Analytical
Quality
MES
ERP
PLM
Development Management
TechTransfer
Clinical I Clinical II Clinical III
Commercial
Experiments
Process UnitProcedures
Product Life CycleProduct Life Cycle
Commercial Scale
Source: Mike Power, BearingPointProductProduct
DemandDemand SupplySupply
4Dynamic Information Now for Everyone©2008 JustSystems
Business Processes Impacting Time-to-Market:Business Processes Impacting Time-to-Market:Early Stage Product and Process Innovation Early Stage Product and Process Innovation
Knowledge of Knowledge of FutureFuture Manufacturing Manufacturing EnvironmentEnvironment
• Result = foundation of process knowledge• Goal = predict manufacturing performance under
commercial operating conditions
Manage Process
Knowledge Creation
Knowledge Knowledge of Chemistry,of Chemistry,Microbiology,Microbiology,PhysicsPhysics
ProcessProcessRequirementsRequirements• Meets cGMP?Meets cGMP?• Safe?Safe?• CommerciallyCommercially viable?viable?
common information modelsManage Process
Knowledge Discovery
Early Stage Product and Process Development: Lab to Bench Scale Pilot
Source: Alison Smith, AMR Research
Rapid IterationsRapid Iterations
ProductProduct
DemandDemand SupplySupply
5Dynamic Information Now for Everyone©2008 JustSystems
ProductProduct
DemandDemand SupplySupply
Business Processes Impacting Time-to-Market: Business Processes Impacting Time-to-Market: Late Stage Process Development Late Stage Process Development through Ramp to Commercial Manufacturingthrough Ramp to Commercial Manufacturing
Foundation of Foundation of preliminary preliminary process process knowledgeknowledge
Experience in Experience in ExistingExistingManufacturing Manufacturing EnvironmentEnvironment
Process ImprovementsProcess Improvements• Improves yield?Improves yield?• Reduces variability?Reduces variability?• Commercially Commercially
viable?viable?
Pilot to Scale Up for Commercial Production
Continuous Improvements / Refinements within Design Space
12 – 36 mos.
common information models
Manage Process Knowledge Sharing Manage Process
Knowledge Retention
Manage Applying Process Knowledge
Opportunity!
Source: Alison Smith, AMR Research
6Dynamic Information Now for Everyone©2008 JustSystems
Opportunity to use ISA-88 recipe as the common information
model for process definitions?
““Master Data”: Master Data”: Coordination Points for ManufacturingCoordination Points for Manufacturinginclude both Product and Process include both Product and Process
Supply
Demand
Product Design/FormulationDesign/Formulation
Marketing CollateralMarketing Collateral
Service DocsService DocsData SyncData Sync
E-CommerceE-Commerce
Order Acquisition & ManagementOrder Acquisition & Management
Supply ChainSupply ChainPlanning (mBOM, Routing)Planning (mBOM, Routing)
Sourcing & ProcurementSourcing & Procurement
ProductPackage Design/ Label Package Design/ Label
ClaimsClaims
Recipe ManagementRecipe Management
Detailed RoutingDetailed Routing
Bill of EquipmentBill of Equipment
Bill of ProcessBill of Process
Bill of Compliance/ CoABill of Compliance/ CoA
Bill of TestBill of Test
Asset MaintenanceAsset Maintenance
Bill of MaterialsBill of Materials
Process SpecificationsProcess Specifications
Process EngineeringProcess Engineering
Maintenance PlansMaintenance Plans
SOPsSOPs
Asset Performance ManagementAsset Performance Management
Opportunity to use ISA-88 recipe as the common information
model for process definitions?
Opportunity to use ISA-88 recipe as the common information
model for process definitions?
comm
on information m
odels
7Dynamic Information Now for Everyone©2008 JustSystems
ISA-88 OperationsISA-88 OperationsIce Cream Recipe ExampleIce Cream Recipe Example
The Blend Ingredients Operation - eight phases associated with blending ingredients.
Note there is no rule on running only one phase at a time. In fact, it is very common for multiple phases to be running simultaneously.
Recipe represented in an industry standard ISA-88 SFC
(sequential function chart)
8Dynamic Information Now for Everyone©2008 JustSystems
A Solution for Faster Time to MarketA Solution for Faster Time to Market
• Process Definition Management• Define all recipes in a common
information model• Build a library of Reusable Manufacturing
Actions• Assemble new Recipes from components
in library
• Benefits:• Standardize on Good Manufacturing
Practices• Feedback loop from Manufacturing to
Development• Improved technology transfer• Process Knowledge Management • Bottom line: Quality by Design, Faster
time to market
Development Process Library
Execution Systems
Operator Instructions
Submission Ready Components
Contract Manufacturing
Structured Data Sources
Common Steps & Actions
Common Steps & Actions
Commercial Process Library
9Dynamic Information Now for Everyone©2008 JustSystems
Key Use Cases in Key Use Cases in Process Definition Management Process Definition Management
1. Create Reusable Manufacturing Actions (RMAs)
2. Author Process Definitions (“Recipes”)3. Document Process Parameters4. Transfer Technology 5. Manage Knowledge
Create Reusable
Manufacturing Actions
Author Process
Definitions
Document Process
Parameters
Transfer Technology
Manage Knowledge
10Dynamic Information Now for Everyone©2008 JustSystems
Create Reusable Manufacturing ActionsCreate Reusable Manufacturing Actions
• Challenges:• Process Definition Management requires reuse of codified content
(RMAs or recipe building blocks)
• No best practice for representing recipes and RMAs outside of manufacturing
• No method for implementing reuse
Impacts:Benefits of recipe normalization are not achieved during Discovery and Clinical phases of lifecycle – time and money left on the table
Create Reusable
Manufacturing Actions
Author Process
Definitions
Document Process
Parameters
Transfer Technology
Manage Knowledge
11Dynamic Information Now for Everyone©2008 JustSystems
Author Process Definitions (“Recipes”)Author Process Definitions (“Recipes”)
• Challenges:• No practice for representing process definitions outside of Batch Control
(where ISA-88 is the standard)
• No “purpose-built” tools – just spreadsheets and flowcharts
• Automation requires custom development
• Parameters and flows managed as large documents
Impacts: Low authoring productivity. Authoring recipes takes months.Difficult to track changes at an elemental level. No audit trailAutomation requires software development and maintenance
Create Reusable
Manufacturing Actions
Author Process
Definitions
Document Process
Parameters
Transfer Technology
Manage Knowledge
12Dynamic Information Now for Everyone©2008 JustSystems
Document Process ParametersDocument Process Parameters
• Challenges:• Parameters authored separately from process flows • Spreadsheets are the current best practice – but are 1000s of rows long• No way to link to or standardize “Bills of X”• No established best practice for regulatory reporting of CTQ / KTQs
Impacts:Low authoring productivity, no way to track/maintain parameters
No element-level change management or audit trail
Disconnected from systems of record
Difficulty supporting Quality by Design
Create Reusable
Manufacturing Actions
Author Process
Definitions
Document Process
Parameters
Transfer Technology
Manage Knowledge
13Dynamic Information Now for Everyone©2008 JustSystems
Technology TransferTechnology Transfer
• Challenges:• Process definitions are represented in human-readable documents, not
available as data
• Recipes need to be manually entered into Batch Control and execution systems
Impact:Ineffective and inefficient technology transfer
QualityYieldCycle time
Create Reusable
Manufacturing Actions
Author Process
Definitions
Document Process
Parameters
Transfer Technology
Manage Knowledge
14Dynamic Information Now for Everyone©2008 JustSystems
Process Knowledge ManagementProcess Knowledge Management
• Challenges:• Document-based approaches to recipe representation
• Discovery requires full-text keyword search
Impacts:Barriers to information discovery and knowledge sharing
Sharing of Good Manufacturing Practices is manual, uneven – lost productivity, gains are not repeatable
No common method of representing “manufacturing process IP”
No mechanism for IP management
Create Reusable
Manufacturing Actions
Author Process
Definitions
Document Process
Parameters
Transfer Technology
Manage Knowledge
15Dynamic Information Now for Everyone©2008 JustSystems
What is the Recipe for What is the Recipe for Addressing these Issues?Addressing these Issues?
• Create a purpose-built process definition editor
• Make documents “componentized”
• Enable valuable content to be extracted and reused from recipes (for knowledge management, RMA, etc.)
• Use SFC flowcharts as the means for navigating and accessing the process parameters
• Make recipes “machine readable”
16Dynamic Information Now for Everyone©2008 JustSystems
Solution: Solution: xfy Process Definitionxfy Process Definition
• ANSI/ISA 88 for standard look and feel for the “flowchart” user experience
• Click on flowchart elements to define critical parameters in forms-based dialogs
• BatchML for data representation• Purpose-built process definition
editor supports key use cases
Create Reusable
Manufacturing Actions
Author Process
Definitions
Document Process
Parameters
Transfer Technology
Manage Knowledge
17Dynamic Information Now for Everyone©2008 JustSystems
What is ISA-88 (“S88”)?What is ISA-88 (“S88”)?
• Standard for:• Graphical representation of batch manufacturing
processes• Data representation
• Three models: physical, process, and control• Widely adopted in Batch Control and MES systems,
so familiar to process engineers
Impact:Easy to use notationStandardizes the representation of recipes upstream of manufacturing steps in the lifecycle
18Dynamic Information Now for Everyone©2008 JustSystems
What is BatchML?What is BatchML?
• Standard maintained by the World Batch Forum for XML representation of data for all three ISA-88 models
• Machine readable – supports transfer of ISA-88 data between systems
• As an XML format, can be “rendered” to human-readable forms (e.g. a user interface or documents or both)
Impact:Captures all ISA-88 data including flows and parameters in a single format
Can be rendered to GUI as ISA-88, trees, forms; or to documents including eCTD for submissions, batch records, etc.
Provides a mechanism for content reuse – Recipe Building Blocks – which is critical to recipe normalization
Solves the technology transfer problem
19Dynamic Information Now for Everyone©2008 JustSystems
The xfy Process Definition SolutionThe xfy Process Definition Solution
BatchML storage of
recipes and recipe building
blocks
ISA-88 Editor for visual editing and navigation
of Process Definitions
Drawing palettes for
ISA-88 shapes and reusable components
Double-click on shapes to drill
down, add process
parameters
20Dynamic Information Now for Everyone©2008 JustSystems
ProcessDefinition
Pilot Scale
Early Development Late Development
Project Management
LIMS / SDMS
QMS / CAPA
Lab Scale
ElectronicLab
Notebooks
Users
Project Operations
Scientists Chemists
BiologistsPharmacistsEngineers
TechniciansOperators
Support
Analytical
Quality
MES
ERP
PLM
Development Management
TechTransfer
Clinical I Clinical II Clinical III
Commercial
Experiments
Process UnitProcedures
Product Life CycleProduct Life Cycle
Commercial Scale
Source: Mike Power, BearingPoint
Process definition tools facilitate early process development
1
Process definitions refined, tech transfer at every point of scale
2 4
Tech transfer improved through machine-readable BatchML
Process definitions transformed into ISA-88 control recipes in MES or Batch Control System
5
Manufacturing knowledge transferred to development through library of reusable process actions
6
ISA-88 recipes used for Description of
Manufacturing Process & Process Controls
(section 3.2.S.2.2) of CTD.
3
21Dynamic Information Now for Everyone©2008 JustSystems
xfy Process Definition Editor
Key Benefits• More rapidly create, edit, visualize, reuse data in recipes• Create / capture / reuse process knowledge • Facilitate Quality by Design• Improve CTD submissions• Improve technology transfer• Collaborate with CMOs• Accelerate time-to-market
22Dynamic Information Now for Everyone©2008 JustSystems
• Global Presence• 1,000 employees, FY ‘07 revenues of $110M
• HQ in Japan, offices in North America (NJ, Vancouver) and Europe (London)
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• Market leader with over 2,500 customers
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2,500 Customers,Marquee Brands
JustSystems
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