Excellence by Design (EbD) The Case for Change Melissa B. Herkt President & COO, PlantWeb Solutions Group Emerson Process Management May 12, 2010

Excellence by Design (EbD)The Case for Change

Melissa B. HerktPresident & COO, PlantWeb Solutions GroupEmerson Process ManagementMay 12, 2010

The Productivity ChallengeThe Productivity ChallengeIndustry Performance TableIndustry Performance Table

Roger Benson – ISPE Manchester 2003Source: Gold Sheet Jan 2009

99.6%

96%

85-95%

92%

74%

30%

3 - 514

50

8 hrs48 hrs

720 hrs

World Class

Pharm Best

Pharm Norm

OTHER METRICS Life Sciences World Class

Production Lead Time 120-180 days 1-7 days

Finished Goods Inventory 60-90 days 10-40 days

Annual Productivity Improvement 1-3% 5-15%

Right-first-timeProduction

Overall Equipment Effectiveness

Stock Turns Cycle Time

Where are the Opportunities?Where are the Opportunities?

“Follow the Money”

Material

Employment

Maint & Util

Depreciation

50%

25%

15%

10%

How Does Pharma Compare to Others?How Does Pharma Compare to Others?

Industry

Oil Refining

Bulk Chemicals

Fine Chemicals

Pharmaceuticals

Mass Productivity, Kg Product/Kg Total ex H2O

>90%

20 – 50%

2 – 20%

1 – 4%

Source: Raymond H Scherzer, Senior Vice President, Engineering, Technology & Capital Management GSK

What Industry Leaders Have Said About OpX / PAT ?

What Industry Leaders Have Said About OpX / PAT ?

“Before you can achieve a high level of operational excellence, you’ve got to nail down predictability.” Dr. P. Yang, EVP Product Ops, Genentech

“Modeling is an extremely important part of the plan … predict what will work in manufacturing, rather than learning the hard (and expensive) way, through wasteful ‘practicing’.” P. McKenzie, former BMS executive

On top level support for PAT – “We’ve been lucky to have leaders who believe you should question the status quo in manufacturing and that recent philosophies coming from the FDA have some credence.” S. Hammond, PAT leader, Pfizer

Let’s Talk About ‘Business’Let’s Talk About ‘Business’ From molecule to medicine, the Life Science company

reason for the journey is sales and profits. Factors guiding the journey are:– Speed … nimble, resilient, being ‘first’– Productivity … more NDAs per dollar of R&D investment– Predictability … right the first time, all the time– Quality by Design (QbD) … Excellence by Design (EbD)– Risk Management / Mitigation– Disruptive Events … early detection and move toward prevention– Best Cost Producer … once the realm of generic manufacturers,

now a must for all companies Since PAT and QbD implementation produce

measurable business results, everyone will adopt and deploy … Right?

The Case for Change to EbDThe Case for Change to EbD Market dynamics and global economic conditions challenge

companies’ performance … industry pressures:– Government run Healthcare– Patent expiration … $140 B by 2012 … generics– Few blockbusters…..personalized medicine– Higher costs for discovery / development / manufacturing– Competition– Quality

Regulators supporting the opportunity for change but uptake is slow

Companies must not just survive, they must prosper … for shareholders and patients

EXCELLENCE BY DESIGN (EbD)

Vision Resources SkillsAction Plan No Change

Resources Skills IncentivesAction Plan Confusion

Vision Resources IncentivesAction Plan Anxiety

Vision Resources Skills Incentives False Start

Vision Skills IncentivesAction Plan Frustration

Steps To Successful ChangeSteps To Successful Change

Vision Resources Skills IncentivesAction Plan

Change

The Vision - ProgressThe Vision - Progress FDA issues Pharmaceutical cGMPs for

the 21st Century – A Risk Based Approach ASTM E55 formed (290+ members) FDA issues PAT – a Framework for

Innovative Pharmaceutical Development, Manufacturing, and Quality Assurance

ISPE Annual Meeting – QbD Operational Excellence (OpX) Congress

– Improve manufacturing and R&D performance / productivity

Draft Validation Guidance (PAT flavor)

August 2002

2003

September 2004

November 2005

January 2006

In Progress

Vision Resources Skills Incentives ChangeAction Plan

Difficulty “connecting the dots” … components are available but no single right way

FDA communications are guidance rather than regulation … companies are risk intolerant

‘Push – Pull’ dilemma … industry should demand rather than have suppliers set the direction

Organizational change requires inspirational leadership … a champion for change … missing in many Life Science companies

Who in your company has the passion, power, patience to “Git-R-Done”?

The Vision - ChallengesThe Vision - Challenges


The Vision – Addressing the Challenges Emerson and Life Sciences

The Vision – Addressing the Challenges Emerson and Life Sciences

Emerson serves 25 of the top 25 Life Sciences companies globally– 50% ask ‘what do you plan?’ or ‘what do you have?’– 15% have a stated strategy for PAT– 10% are trying to influence our direction (Emerson

does R&D too!) In addition to new products, Emerson invests by:

– Developing solutions that are easy to use and implement

– Establishing strategic PAT partnerships– Creating operational readiness


Resources - ProgressResources - Progress FDA encouraging industry to adopt QbD and PAT

constantly and consistently Attendance at PAT industry events now have business

leadership attendance in addition to scientists Business cards now have PAT in titles, particularly at a

Corporate level To date, some NDAs have been submitted incorporating

PAT technologies ASTM E55 committee active and writing standards Suppliers beginning to offer technologies to enable QbD

and PAT and continue to invest in technology development


Resources - ChallengesResources - Challenges Some ‘inward focus’ by industry leadership

… suppliers seeking advice / input / ‘push’ to direct our R&D

PAT has not been broadly embraced by employees throughout companies, outside of the core PAT groups … fear of failure?

Companies are embracing PAT but don’t have the staff to implement programs (Pharmaceutical Manufacturing, April 2010)


Resources – Addressing the Challenges Emerson and Life Sciences

Resources – Addressing the Challenges Emerson and Life Sciences

Hosted FDA speakers at the Life Sciences Industry Forum at Emerson Exchange 2009

Active member of ASTM E55 University program funding

to help bridge the gap Offer training for internal and

customer personnel


Skills - ProgressSkills - Progress FDA is actively training personnel and investing in

marketing to convince industry to embrace QbD and PAT

DeltaV & synTQ used to train FDA Inspectors on PAT at Duquesne University – secondary processes

Life Sciences companies now hiring PAT experts from other industries like Food & Beverage and Chemical

Life Science companies beginning to use process engineering expertise and PAT principles during the research and development process.

Industry consortiums jointly developing mindshare


Skills - ChallengesSkills - Challenges R&D uses different tools in development than those that

will be used in manufacturing … costly / barriers to make changes later

Scientists have tried / proven methods in the lab … can auto-gathered / generated data be trusted?

Companies often do not use process and automation engineering knowledge early enough in the product development

Companies often do not use scientists far enough along into the manufacturing process … some beginning to adopt a holistic approach


Skills – Addressing the Challenges Emerson and Life Sciences

Skills – Addressing the Challenges Emerson and Life Sciences

Market technology choices early

Use PAT to do QbD i.e. – new disposable

bioreactor with wireless technology

Making it easier to use technology to improve operations

Use of enabling technologies to collect knowledge for development and scale up


Incentives - ProgressIncentives - Progress FDA is facilitating change with guidance but not dictating

with regulations. Business must engage and drive the change

WHAT INCENTIVE HAS YOUR COMPANY TO DRIVE

CHANGE?


Research

Development

Pilot / ClinicalManufacturing

Bulk Manufacturing

Final Dose

Risk?

Risk?

Risk?

ChallengesKnowledge Transfer … Quality …

Regulatory Compliance … Commercialization

Risk?

Risks on the Path from Molecules to Medicine

Incentives - ChallengesIncentives - Challenges


Reaction, Repeatability, Scale Up, Knowledge Transfer

Reaction, Repeatability, Scale Up, Manufacturability, Knowledge Transfer, Purification Process, Formulation

Reaction, Repeatability, Scale Up, Manufacturability, Knowledge Transfer, Purification Process, Critical Process Parameters, Best Cost Producer

DevelopmentResearch

Pilot / ClinicalManufacturingDevelopment

Bulk Manufacturing

Pilot / ClinicalManufacturing

Final DosePilot / ClinicalManufacturing

Formulation, Repeatability, Scale Up, Manufacturability, Knowledge Transfer, Critical Process Parameters, Best Cost Producer

Risks increase and change over time

Risks on the Path from Molecules to MedicineRisks on the Path from Molecules to Medicine




Without defined goals, metrics, and incentives to drive organizational and individual change, slow uptake of PAT will continue

Targeted programs to drive new technology and select methods to achieve vision without increasing risks must be implemented

Scientists and engineers need organizational support and incentives to embrace and drive change


Incentives – Addressing the Challenges Emerson and Life Sciences

Incentives – Addressing the Challenges Emerson and Life Sciences

Growing our customer base in Life Sciences Creating a Win-Win for customers and

Emerson Enabling customers to get more from existing

investments in technology and facilities Providing solutions!


Action Plan - ProgressAction Plan - Progress

Two thirds of biomanufacturing companies have budgeted plans to implement QbD / PAT (Pharmaceutical Manufacturing, April 2010)

Increased NDA submissions with PAT components

Industry implementing on a small scale basis A small number of companies are driving

solution development


Action Plan - ChallengesAction Plan - Challenges

Is your company defining / demanding innovation from technology providers?

Have you engaged the FDA as a partner to drive change?

Has your company made progress?

WHAT’S NEXT?


Action Plan – Addressing the ChallengesEmerson and Life Sciences


Through technology and expertise, Emerson can help formulate your Action Plan:– Predict ‘end of batch’ quality – Alarm when a deviation occurs

– Provide an operator-friendly

mechanism to identify “probable

cause” for deviations

– Verify reason for deviation and

enable appropriate action

– Proactive impact on quality and

safety!


Process engineer develops a

statistical model to predict quality

– Operator improves control with

predicted values

Process engineer develops

statistical model for fault

detection

– When quality prediction is bad, fault

detection indicates which inputs are

causing problems

– Operator improves quality and is able to

troubleshoot problems without experts

Operator becomes more effective

– On-line quality predictions and fault

detection prevent quality incidents and

downtime

Quality Parameter Prediction

Root Cause

Fault Detection




Vision Resources SkillsAction Plan No Change

Resources Skills IncentivesAction Plan Confusion

Vision Resources IncentivesAction Plan Anxiety

Vision Resources Skills Incentives False Start

Vision Skills IncentivesAction Plan Frustration

Steps To Successful ChangeSteps To Successful Change


Change

Will We Change???

SummarySummary Embrace EbD … accept nothing less! 5 key elements to successful change … identify and

address missing elements

PAT adoption must be driven by Life Science companies FDA is facilitating and encouraging PAT adoption Technology providers like Emerson can and have

contributed to the PAT initiative and are willing to invest in R&D to meet Life Science company needs … please DO influence and define industry needs


Change

Documents

Excellence by Design (EbD) The Case for Change Melissa B. Herkt President & COO, PlantWeb Solutions Group Emerson Process Management May 12, 2010