From Industrie 4.0 to Pharma 4.0 Operating model and The...

transcript

From Industrie 4.0

to Pharma 4.0 Operating model and

The Holistic ICH Control Strategy

Christian Wölbeling

ISPE SIG “Pharma 4.0” Founder & Chair

for the ISPE Special Interest Group/SIG “Pharma 4.0”

c/o Werum IT Solutions GmbH

Christian WoelbelingSenior Director Global Accounts

Werum IT Solutions GmbH

+49 4131 89 00 490

christian.woelbeling@werum.com

My Background…

Market Leader

in MES for Pharma & Biotech

❑ SIG Pharma 4.0 Founder & Chair

❑ GAMP Europe Steering Member at Large

❑ GAMP MES SIG Co-Chair

❑ KNC Council Chair

❑ Global Steering Team Member CoP „PAT & LCS“

❑ Affiliate Germany-Austria-Swiss / DACH Board Member

…25 Years Pharma Industry Experience

Connecting Pharmaceutical Knowledge ispe.org 2

1. Problem Statement

❑ 6 Sigma Quality in Pharma

2. The Pharma 4.0 Operating Model

❑ Elements

❑ Enablers

3. The Holistic Control Strategy

❑ Digitalization of the Pharmaceutical Quality System (PQS) / ICH Q10 - Based on ICH Q8 – 12

4. Benefit of the Holistic Control Strategy

❑ Shorter Time to Market – Reduced Inventory

5. Summary & Conclusions

From Industrie 4.0 to Pharma 4.0 Operating Model and

The Holistic ICH Control Strategy

PROBLEM STATEMENT

QUALITY ISSUE?!?

What is the Fundamental Problem? – Quality & Performance!

Source: Lawrence Yu, Ph.D. Deputy Director, Office of Pharmaceutical Quality FDA Center for Drug Evaluation andResearch

Future of Pharmaceutical Quality and the Path to Get There, 3rd PQRI/FDA Conference on Advancing Product Quality, March 22-24,2017

Drug Shortages FDAApp:

The FDA Loops Back to 2004...Did we Advance?Hurray...PAT & Quality by Design Revival!

The 2nd Wave of Quality byDesign!

Vision

Vision & Mission StatementISPE SIG “PHARMA 4.0” Strategy

Source: FDA Presentationat ISPE Conference,Washington,June 2015

Mission

“Manufacture pharmaceutical products with

maximum product & process understanding,

data integrity by design, efficiency and optimal

resource allocation on the basis of full

digital data transparency - to the benefit of

the patient.”

ISPE, Special Interest Group “Pharma 4.0”

THE PHARMA 4.0 OPERATING MODEL

FROM INDUSTRY 4.0 TO PHARMA4.0

Where we are coming from...Industrie 4.0 & ICH Q8 – 12

Q8 Pharmaceutical Development

Q11 Development and Manufacture of

Drug Substances

Q9 Quality Risk Management

Q10 Pharmaceutical Quality System

Q12 Product Life Cycle Management / PLCM

https://www.acatech.de/Publikation/recommendations-for-implementing-the-strategic-initiative-industrie-4-0-final-report-of-the-industrie-4-0-working-group/

Future ICH Qx Guidelines

From Industrie 4.0 to PHARMA 4.0 Operating ModelDefinition

The PHARMA 4.0 Operating Model

enables and controls the Holistic Control

Strategy Lifecycle Management with

Data Integrity by Design based on the

organizations Digital Maturity within the

Industrie 4.0 architectural framework.

Source: ISPE SIG “PHARMA 4.0”

PHARMA 4.0 OPERATING MODEL ENABLER

DIGITAL MATURITY

MATURITY MODEL

The Overall Corporate & Value Network Structure

https://www.acatech.de/Publikation/recommendations-for-implementing-the-strategic-initiative-

industrie-4-0-final-report-of-the-industrie-4-0-working-group/

PHARMA 4.0 – Operating Model

Strategy and Managementof

Producing Companies.

A VDI book.ISBN 978-3-642-14501-8

https://www.acatech.de/wp-content/uploads/2018/03/acatech_STUDIE_Maturity_Index_eng_WEB.pdf

Key Enabler – Digital Maturity

VALUE NETWORK MODELSTRUCTURALAREAS

Six Maturity Levels

Computerization

Connectivity

Visibility

Transparency

Predictability

Adaptability

Matching the Industry 4.0 Model with the FDA Digital Maturity Model

Source: Lawrence Yu, Ph.D. Deputy Director, Office of Pharmaceutical Quality FDA Center for Drug Evaluation and Research

Future of Pharmaceutical Quality and the Path to Get There, 3rd PQRI/FDA Conference on Advancing Product Quality, March 22-24, 2017

Adaptability

Predictability

Transparency

Visibility

Connectivity

Computerization

PHARMA 4.0 OPERATING MODEL ELEMENT

RESOURCES

DIGITALIZATION WORKFORCE 4.0 ROBOTSAVAILABLE AND QUALIFIED

Connecting Pharmaceutical Knowledge ispe.org

Resources are tangible, physical assets.

These include a company’s

❑ workforce (human resources with new skill sets)

❑ machinery / equipment

❑ infrastructure

❑ tools

❑ materials and

❑ the final product.

PHARMA 4.0 – Operating ModelResources

❑ Human / Machine Interface

❑ Digital learning

❑ Speech recognition

❑ Augmented & virtual reality

❑ Chat robots

❑ Artificial Intelligence

Source: Acatech Study

INFORMATION SYSTEMS

HOLISTIC VALUE NETWORK INTEGRATION AND TRACEABILITY

Information systems are socio-technical systems in which information is provided based on

❑ economic criteria by both people and

❑ information and communication technology.

❑ Prepare,

❑ Process

❑ Store and

❑ transfer data and information.

PHARMA 4.0 – Operating ModelInformation Systems

PHARMA 4.0

ERPSystems

MESSystems

Systems

Logistics Systems

Digital Product Lifecycle System

Historian

Building Management

Equipment

PLCSensors

Maintenance Management

LIMCSommercialMHPaLnCufacturing

PharmaceuticalDDMSevelopment Technology Transfer IFnilevsestigational Products

PHARMA 4.0 – Operating ModelInformation Systems – Analytics & Predictive Control

Big Data: 3 Dimensional Holistic Integration

Integrated Enterprise Production Data

Across Sites and CMOs

APR / PQR – “...at your fingertips”

Analyze & Correlate Data

For Predictive Control

All Systems like ERP, LIMS, MES, CAPA, SCADA etc.

Production Data Lifecycle Management

Analyze Big Data across the Product Life Cycle

PHARMA

CULTURE

COMMUNICATIONDECISION MAKING

PHARMA 4.0 – Operating ModelCulture – “Quality is not an Organization”

❑ Digital mindset

❑ Pharma 4.0 is more than technical

❑ Different leadership skills (software factors, listening)

❑ Risk Management culture

❑ Accept decisions

❑ “Culture eats Strategy for Breakfast”

Culture covers the value system within

the company and thus describes the soft

factors of collaboration. Nevertheless,

both (Organization & Culture) structural

areas are mutually dependent and must

be coherent with each other.

ORGANIZATION & PROCESSES

ICH HOLISTIC CONTROL STRATEGYLIFECYCLE MANAGEMENT

Organizational structure refers to both a

❑ company’s internal organization (structure and operational processes) and

❑ its position within the value network.

In contrast to area of “culture”, the “organizational structure” establishes mandatory rules that organize collaboration both within the company and externally.

PHARMA 4.0 Operating ModelOrganization & Processes

❑ Flexible Communities

❑ What training is needed for the digital

culture (new formats of training)

❑ harmonization of technical processes

❑ switch from hierarchical to process thinking

❑ data stored in silos – to be changed to one

data source – “one source of the truth”

❑ introduction of lifecycle approach

PHARMA 4.0 OPERATING MODEL ENABLER

DATA INTEGRITY BY DESIGN

RISK BASEDAPPROACHCRITICAL THINKING

PHARMA 4.0 Operating Model

❑ Data Flow Diagrams❑ Data that is necessary for correct decisions

❑ e.g. Global Audit Trail Standards

❑ Along the Data Lifecycle❑ According to regulatory retention time

Key Enabler – Data Integrity by Design

Prerequisite:

Business Process Descriptions and

HarmonizationDo you know your Business Processes?

❑ Based on ISPE GAMP:

“Records and Data Integrity GUIDE”, March 2017

❑ Process Flowcharts

Source: ISPE GAMP: “Records and Data Integrity GUIDE”, March 2017

PHARMA 4.0 OPERATING MODEL

HOLISTIC CONTROL STRATEGY

DIGITALIZATION OF THEPHARMACEUTICAL QUALITY SYSTEM (PQS)/ ICH Q10

BASED ON ICH Q8 - 12

FDA & ICHRoadmap & History of the Term Control Strategy

Risk & Science based Approach

of the FDA & EMA:

▪ ICH Q 8 (R2) Pharmaceutical Development (2005/2009)

▪ ICH Q 9 Quality Risk Management (2005)

▪ ICH Q 10 Pharmaceutical Quality System (2008)

▪ ICH Q 11 Development and Manufacture of Drug

Substances (2012)

▪ ICH Q 12 Technical and Regulatory Considerations for

Pharmaceutical Product Lifecycle Management

(Draft November 2017)

▪ ICH Q13 Continuous Manufacturing (Concept)

▪ ICH Q14 AQbD, Analytical Quality by Design(Concept)

Control Strategy, ICH Q10Quality Target Product Profile (QTPP)

Quality Manufacturing Focus – “QTPP - Required for all products...”

A planned set of controls, derived from current product and

process understanding, that assures process performance and

product quality. The controls can include parameters and

attributes related to drug substance and drug product

materials and components, facility and equipment operating

conditions, in-process controls, finished product

specifications, and the associated methods and frequency of

monitoring and control.

The control strategy plays

a key role in ensuring that

the CQAs are met, and hence

that the QTPP is realized.

PHARMA 4.0

Material and Product Control

Process Control

Commercial Process

Facility, Equipment, IT, Automation,

The Changing Focus of the Control Strategy

End to End Integrated Holistic Control Strategy Lifecycle Management

Control Strategy:

New Drug Application / Submission

Manufacturing Control Strategy:

Execution Engine

Control Strategy

❑ Product-related

❑ Based on ICH Q8/Q10

❑ Established during development, part of the NDA

Manufacturing Control Strategy

❑ Process-related

❑ Defines Master Batch Record

❑ Enables ongoing or Continued Process Verification/CPV

Holistic Control Strategy

❑ Systematic and controlled concept for developing and managing information throughout the lifecycle

❑ End-to-End view (Holistic Product Lifecycle ManagementApproach)

Control

Strategy

Manufacturing

Control Strategy

Holistic Control

Strategy

Definitions

Pharmaceutical Quality System – ICH Q10

Product

Discontinuation

Commercial

Manufacturing

Technology

Transfer

Pharmaceutical

Development

Investigational Products

Management Responsibilities

Process Performance & Product Quality Monitoring System

Corrective Action/ Preventative Action (CAPA)System

Change Management

Management Review

Knowledge Management (KM)

Quality Risk Management (QRM)Enablers

Elements

ICH Q10 PQS needs additional elements and enablers with Pharma 4.0 Digitalization of the ICH Q10 PQS

PHARMA 4.0:

Digital Maturity & Data Integrity by Design

ICH Q10: Knowledge Management & Quality Risk Management

ICH Q10: Process Performance & Product Quality Monitoring SystemPQS

Elements

Corrective Action

Preventative Action (CAPA) System

Change Management

Management Review

Enablers

ICH Q10: Management Responsibilities

Holistic Product Control Strategy Lifecycle Management / PLCM

PHARMA 4.0:Resources: Digitalization, Workforce 4.0, Available & Qualified

Information Systems: Holistic Value Network Integration & Traceability

Organization & Processes: Holistic Control Strategy Lifecycle Management

Culture: Communication & Decision Making

Enablers

New PQS

Elements

Commercial Manufacturing Product DiscontinuationPharmaceutical Development Technology Transfer

Investigational Products

Control Strategy Manufacturing Control StrategyMethodology

Pharma 4.0 Digitalization Strategy:

Best Practice Holistic Control Strategy Implementation Methodology

Knowledge Led Best Practice Methodology

Pharma 4.0

Control Strategy:

New Drug Application

Manufacturing Control Strategy:

Execution Engine

Business Process Harmonization

Process Maps

Process Data Maps & Data Flow

Vertical & Horizontal Data Integration

Risk Based Approach / CriticalThinking

Transfer to CMOs

ICH Q10 based Process Performance & Product Quality Monitoring System

Applying Data Integrity by Design

Commercial ManufacturingPharmaceutical Development Technology Transfer Investigational Products

BENEFIT OF THE HOLISTIC CONTROL STRATEGY

SHORTER TIME TO MARKET

REDUCED INVENTORY

Risk Level & Conventional Control Strategy Approachincl. Process Validation ViewLevel of risk

Product Life

Control

Strategy

Facility

Control

Strategy

Initial

Control

Strategy

Production

Control

Strategy

Acceptable

level of risk

Commercial

Manufacturing

Process Design

Development

Process Qualification

Qualification & Process Validation

Continued Process Verification

Ongoing Process Verification

Pharmaceutical product & process development

Process engineering, automation, tech transfer, Validation, ramp-up,qualification,

training

Commercial manufacturing, continual improvement, business optimisation,

lifecycle managementIndustry

Source: Line Lundsberg-Nielsen, NNE, February 2018

Risk Level & Holistic Control Strategy ApproachHolistic Control Strategy Lifecycle Management / Enterprise Recipe Management

Control

Strategy

Facility

Control

Strategy

Initial

Control

StrategyProduction

Control

Strategy

Acceptable

level of risk

Manufacturing

Process Design

Development

Continued Process Verification

Ongoing Process Verification

Pharmaceutical product &

process development

Process Qualification

Qualification & Process Validation

Process engineering, automation, tech transfer,

Validation, ramp-up, qualification, training

Commercial manufacturing, continual improvement, business optimisation, lifecycle management

Industry

Commercial ManufCaocmtmuerirnciagl

Source: Line Lundsberg-Nielsen, NNE, February 2018

Shorter Time to Market

Reduced Inventory

Level of risk

Product Life

Enabled by

Digitalization

HOLISTIC CONTROL STRATEGY IN CELL & GENE THERAPY

BENEFIT OF MANAGINGCOMPLEXITY & FLEXIBILITY

Pharma 4.0 Early Adopters From Start Up...Use Case Patient to Patient...Digitalized

Source: Bradley Glover, 12/4/2017, ISPE Biotech Conference, San Francisco, CA

New Digitalized Complex Supply Chains: Example Manufacturing Process: CAR-T

SUMMARY & CONCLUSIONS

Interdisciplinary Collaboration is Key! Silo Breaking...

Product

Development

Design

Commercial

Manufacturing

Execution

Engineering

Automation & IT

Realization

Holistic

Control

Strategy

Transfer

Innovation Maintenance

Management Responsibilities: Accurate Decision Making

Quality Culture Excellence

Impact

& Maturity Model

& Produce

Management Communication

Strategy

Process Maps

& Critical Thinking

Holistic

Control

Strategy

Validation 4.0

Bridging the ISPE Pharma 4.0 Operating Model with the SIG Working Groups

Read more about the ISPE “PHARMA 4.0 Operating Model”3 Pharma 4.0 Articles in the PE May / June 2019 Issue

❑ Holistic Control Strategy Approach

❑ Digitalization of the ICH Q10 PQS

❑ Pharma 4.0 is not an IT Project

❑ Pharma 6Sigma Quality Approach

❑ Regulatory Expectations Management

❑ Apply Emerging Technologies e.g. CPV

❑ Digitalization enables Decision Automation

❑ Turn Data into Knowldege & Wisdom

❑ AI driven / supported GMP decisions

Summary & Conclusion

Christian Woelbeling

Werum IT Solutions GmbH

+49 4131 89 00 490

christian.woelbeling@werum.com

Thank you for your attention!

Special AcknowledgementsISPE SIG “Pharma 4.0” Members:

Lorenz Binggeli

Lothar Hartmann

Hans Heesakkers

Uli Kuchenbrod

Line Lundsberg-Nielsen

Volker Roeder

Thomas Zimmer

ISPE: Let’s shape the future of life sciences together !

From Industrie 4.0 to Pharma 4.0 Operating model and The...

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