Life Sciences Manufacturing Transformation · Life Sciences Manufacturing Transformation Bob Lenich Life Sciences Marketing Director, Emerson. Presenter: ... committee and the six

Life Sciences

Manufacturing

Transformation

Bob Lenich

Life Sciences Marketing Director, Emerson

Presenter:

Bob Lenich

• Emerson Automation Solutions Life Sciences Marketing Director

• >35 years in the Life Sciences automation industry

• Wide experience applying technology to solve manufacturing operation problems

• B.S. in Chemical Engineering: Rose Hulman Institute of Technology

• M.B.A. University of Texas at Austin

• Contact info:

– Emerson Automation Solutions | 1100 W. Louis Henna Blvd. | Building 1 | Round Rock | TX | 78681 | USA

– T +1 512 834 7033 | C +1 512 350 4002

– [email protected]

– www.linkedin.com/in/bob-lenich

2Emerson Confidential

Emerson Confidential

Pharmaceuticals Need to Change3

“The pharmaceutical industry has been slow to adopt

approaches embraced by other industries, but I think the time

is now,”

FDA Commissioner Margaret Hamburg

touring Vertex’s continuous manufacturing line 1

1 WSJ Feb. 8, 2015 Drug Making Breaks Away from It’s Old Ways


Pharmaceuticals Need to Change4

1 https://blogs.fda.gov/fdavoice/index.php/2018/07/fda-budget-matters-investing-in-advance... 7/13/2018

“There’s new technology that can improve drug quality, address shortages of medicines, lower

drug costs, …At the FDA, we’re focused on propelling these

innovations, collectively referred to as Advanced Manufacturing.”

FDA Commissioner Scott Gottlieb

FDA Voice July 13, 2018 1

Financial Incentives to Change


‘Right First Time’

14%More First-Pass

Quality Yieldfor top quartile

WIP Inventory Turns

Primary Product Manufacturing Cycle Time Capacity Utilization

36 hrs

7 hrs

4th 1st

5XFaster Cycle Time

for top quartile

84%

98%

4th 1st

9

19

4th 1st

2XFaster Inventory

Turnsfor top quartile

80%

90%

4th 1st

12.5%Higher Capacity

Utilizationfor top quartile

Quartiles

Quartiles

Quartiles

Quartiles

Source American Productivity and Quality Center

Overall Life Sciences Industry Trends Driving the Transformation1

6

Cost Containment / Controls

Manufacturing Increasing in Developing Countries

World-wide Standardization of Manufacturing

• Growing protests over high pharmaceutical prices

• Drugs are curative but set records for costs

• Outside of the US, government-imposed price controls are common

• Price controls restricting innovative R&D

• New and increased manufacturing capacity is being added internationally

– Especially in China, India, and other Asian countries

• Mostly for domestic, regional, or lesser / non-regulated international commerce

• Local governments are seeking to assure domestic manufacturing

• Larger companies continue to standardize their products and manufacturing processes on a world-wide basis

• Targeting 2nd and 3rd source geographically spread facilities

– Example: major facilities in US, Ireland and Singapore

• Adoption of Single-Use and Modular systems are accelerating

Emerson Confidential1 Report and Survey of Biopharmaceutical Manufacturing and Production, April 2018


One Path Forward:

BioPhorum

8

Member Companies

• Abbvie

• AGC Biologics

• Ajinmoto

• Aldveron

• Alexion

• Allergan

• Amgen

• Applied Materials

• Asahi Kasei

• AstraZeneca

• Avantor

• BASF

• Bayer

• Becton Dickinson

• Biogen

• BioMarin

• Bristol-Myers Squibb

• Boehringer Ingelheim

• Brammer Bio

• Catalent

• Celgene

• Chugai Pharmaceutical

• CPC

• CRB

• CSL Behring

• Dow

• Eisai

• Eli Lilly

• EMD Serono

• Emerson

• Endress+Hauser/Kaiser

• Entegris

• Ferring

• Friesland Campina

• Fujifilm Diosynth

• G-CON Manufacturing

• GE Healthcare

• Gilead

• GlaxoSmithKline

• Honeywell

• ImmunoGen

• Ipsen

• Janssen

• Juno Therapeutics

• Kyowa Hakko Kirin

• Lonza

• M&W Group

• Meissner Filtration

• Merck MSD

• Merck KGA

• Millipore Sigma

• NewAge Advantapure

• Novo Nordisk

• Pall Life Sciences

• Pfizer

• PM Group

• Regeneron

• Roche / Genentech

• Rockwell Automation

• Samsung Biologics

• Sanofi

• Sartorius Stedim

• Shire

• Siemens

• Sigma Millipore

• Takeda

• Thermo Fisher

• UCB

• Waters Corp


>2200 Active Participants

The six Phorums Provide Benefits Across the Biopharma Supply Chain

Drug Substance, Fill Finish, Development Group, Information Technology

• Accelerating the way the industry delivers near term results, making best practice development and implementation faster, cheaper and smarter

Supply Partners

• Creating the supply chains the industry needs; defining, developing and implementing solutions for business processes, systems and culture

Technology Roadmapping

• Revolutionizing the way the industry develops longer term transformational manufacturing and technology capabilities

• Focusing on strategy and ten year time horizon, defining needs, difficult challenges and potential solutions

Regulatory Interaction

• Enable engagement and alignment with Regulatory Stakeholders in order to accelerate adoption and successful implementation of advances in manufacturing

Facilitation

• Ensures decisions are made at the right time, at the right place by the right people

• Linkages are made visible to avoid redundancy

• Synergies are leveraged through effective coordination


Technology Roadmapping

• Dynamic and collaborative technology management process

– Accelerates innovation

– Defines future needs, difficult challenges and potential solutions

• Active participation by:

– Bio-manufacturers

– Supply partners

– Leading academics

– Regional innovation hubs

– Agencies


Mission of the Technology Road-mapping Phorum:

To Accelerate Industry Innovation

The BPOG technology roadmapping process is a dynamic and evolving collaborative technology management process for:

• Determining precompetitive critical needs and drivers

• Identifying technology and / or manufacturing targets

• Assessing / modeling potential solutions

• Coordinating implementation projects

to

• Focus an industry community

• Provide direction

• Resolve those critical needs for a specific timeframe by consensus

• Ensure that technologies are delivered and adopted


The First Edition Technology Roadmap was Published July 2017 and Continues

to be Accompanied by Extensive Communication

• The First Edition is freely available on the BPOG public website to maximise access & measure it’s reach.– First Edition documents are the result of two years effort by the steering

committee and the six enabling technologies roadmap teams

– Consists of 8 documents covering over 400 pages of content

• Communication within member companies continues to maximise company benefit– Increase participation levels to leverage the roadmap and further

accelerate implementation within member companies

• External communication continues to raise the profile of the roadmap, aligning industry efforts, gaining feedback and increasing number of organisations involved– Conference presentations by the steering committee and roadmap team

experts

– Regular Newsletters

– Press Releases

– Publication of articles in industry press

– Videos and webinars by the teams

– Meetings with Regulators


http://www.biophorum.com/executive-summary/

First Edition Documents

Presentations & Articles

http://www.biophorum.com/executive-summary/


Uncertainty

▪ Regulatory approvals

▪ Demand variability

▪ Competition

Cost pressure

▪ Payer pressure

▪ Biosimilars

▪ Development

Market Growth

▪ Emerging markets

▪ Global reach

▪ In region manufacture

New Product Classes

▪ Non-mAbs, ADCs

▪ Gene therapy

▪ Cell therapy

Modular and Mobile- 70% build time

- 75% CAPEX

▪ Quick to configure &

scale

▪ Standard designs

▪ Streamlined validation

Automated Facility− 50% Facility Build

Speed

− 50% OPEX costs

from current

▪ Agile, high quality, and

robust

biomanufacturing

▪ Plug and Play

▪ Open data standards

▪ Interoperability

Knowledge

Management‒ Cost of process

development

– Time to introduce a

change to an existing

process to 1 Month– Cost of Non-Quality

to 2% of operating costs

• Efficient tech. transfer

• Integrated knowledge

• Quality throughout

lifecycle

Supply Partnership

ManagementSafe, innovative supply

chains:

− Cost of quality

− Time

▪ Partnerships with

quality built in

▪ Standard working,

integration and real

time Electronic Data

Exchange

▪ Shared Planning

Market Trends & Business Drivers – The Why

Enabling Technologies & Capabilities – The How

Speed

-70% build time

-80% lead time

Cost

-90% manufacturing cost

-90% CAPEX

Flexibility

-90% changeover

Demand response

Quality

10x robustness

-90% cost of quality

Drug Product

High volume

Drug Product

Low volume

Scale Distributed

1. Large-scale Stainless Steel Fed Batch

2. Intermediate-scale Single-use Perfusion

3. Intermediate-scale Multi-product Single-use Fed Batch

4. Small-scale <500L Portable Facility

Biomanufacturing scenarios – The What

(Facility types)

5. Small-scale <50L for Personalized Medicine

First Edition Technology Roadmap Vision

Inline Monitoring and

Real time Release- Product Release

1-2 day

+ ↑ Quality, Efficiency &

Supply

▪ Enhanced In-Line

Monitoring

▪ Indirect and

Multivariate Sensors

▪ Multivariate Analysis

and Predictive

Modeling

Process Technologies- 90% CoGs

- 90% process

investment

▪ Process Intensification

& combination of unit

operations

▪ Continuous processing

technologies coupled

with advanced process

control

Roadmap Team has 12 Projects Supporting Technology Needs Identified in the

1st Edition Technology Roadmap


8. Rapid methods for

adventitious virus &

mycoplasma.

Develop/validate new

rapid sensitive

sterility tests

4. Process

Intensification, high

cell density cell

culture processes

5. Reliable & cost

effective cell removal

options for higher

density processes in

biomanufacturing

1/7. Reduce release

testing need because

we have RTR/ILM

2/16. Managing

Product & Process

Knowledge across

the Lifecycle

6. Buffer Preparation

9/10. Data

analysis to evolve

from big data to

smart data

13/14. Robotic

technologies in

biomanufacturing

15. Standard

Facility Design

17. Reduce

suppliers internal

testing

requirements and

release efforts

20. Continuous

Downstream

Processing

Process

Technology

Inline Monitoring

& Real time

Release

Modular &

Mobile

Automated

Facility

Knowledge

Management

Supply

Partnership

Management

21. Plug and Play

1st edition

Global

Roadmap

chapter:

BPOG Technology Roadmap– 2018 ProgramFor detail of each project line, see project charter

15


Jan Mar May Jul Sep Nov

4 – Upstream Process Intensification for high cell density cultures

5 - Reliable & cost effective cell removal Go / No Go decision needed

6 - On demand buffer preparation

20 - Continuous downstream processing

1/7 - Reduced release testing through in-line monitoring

15 - Standard facility design

9/10 - Big Data to Smart Data

13/14 - Robotics Technologies

21 - Plug and Play Automation

2/16 - Managing product and process knowledge across the lifecycle

17 - Relevant specifications for Raw

Materials & Single Use Components

8- Rapid methods for adventitious virus detection and sterility

assurance

1st Edition Technology Roadmap – Communications & Engagement

TR07 TR08

Process Economic Modelling

paperTechnology development

Plan with BPIT

paper

paperTechnology development PoC test

PoC test Next materialspaper

paper

paper

Model development

Technology development

Industry & regulatory strategy

2nd Edition Technology Roadmap

ILM02

F2F

CBP02

MM02

CBP01

AF01

BUFP02

MM01

KM01

BUFP03

2nd Ed Technology

RoadmapUS Roadmap component

content finalised

paper

paper

NIIMBL 1st edition US Roadmap F2FF2F

NIIMBL 2nd edition US roadmapF2F

Roadmap teamsContent generation and review

TRM SteeringProgram strategy, resolution of issues and governance.

TRM Projectso Transformational

for the industry

o Co-implementation of URS and whitepapers

o Standard frameworks

Communities of practice

Regional roadmaps


BPOG Phorum collaboration


Buffer Preparation

Standard Facility Design

Continuous Downstream

Processing

Process Technology

ILM & RTRModular &

MobileAutomated

FacilityKnowledge

ManagementSupply Partnership

Management

Process Development

Operations, Quality &

Compliance

Microbial ControlContamination

free process

Lean Qualification / Validation

Disposables – Change notification

Deviation management

system

Post approval supplement strategies

Human performance

Continued process verification

QC stability

Reliability

Alternatives & rapid micro

methods

Container closure integrity testing

(CCIT)

EM in a modern DP facility

Pre-post use sterilization

integrity testing

Visual inspection / particulate control

Lyophilisation

Digital plant maturity

Smart maintenance

Compliant multi-source analytics

Cloud, IaaS controls

SPITDGFFDSTR RI

Viral clearance

Formulation

Development outsourcing

CMC regulatory

Host cell proteins

How do you demonstrate

monoclonality

Qualification of scale down models

Forced degradation

studies

BioAssay

Knowledge management in

development

CMC considerations for

expedited development

programs

Analytics

Regulatory interaction

Rapid methods for adventitious

detection & assurance

Upstream Process

Intensification

Reliable & cost effective cell

removal

Rapid release testing through

inline monitoring

Knowledge Management

Big Data to Smart Data

Robotics

Relevant specifications for raw materials

Plug and Play

Disposables – Supply base reliability

Disposables – Testing, validation & release

standards

Storage & transport

Stopper quality

Supply chain digital platforms & integration

Supply Chain Mapping

Forecasting and Demand Planning

Raw material variabilityDisposables – E&L

Disposables – SUS URS

Closed systems

Multi-product facilities

Small flexible filler

Risk Mgt and Business Continuity Planning

Joint Audit Program

Industry Capacity Constraints Analysis

Microbial ControlOperational

harmonisation

Data Integrity

Cybersecurity /plant resilience,

recovery

Example Factory of the Future

Unlocking the Value of Advanced Manufacturing Requires Planning

Advanced Manufacturing

in Life Sciences are

progressing.

Assess people,

processes and

technologies within your

organization to determine

how to get the benefits

Approach requires re-thinking your

manufacturing processes and business

Technology barriers are being addressed

Secondary manufacturing is moving the fastest

but primary is also progressing

Requires people with a combination of process

and automation / data technology skills

Requires flexible and adaptable automation and

data management platforms
