Excellence by Design ( EbD ) The Case for Change

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

2. The Productivity Challenge Industry Performance Table World Class Pharm Best 720 hrs Pharm Norm 99.6% 92% 96% 50 74% 85-95% 30% 14 48 hrs 3 - 5 8 hrs Right-first-time Production Stock Turns Cycle Time Overall Equipment Effectiveness Roger Benson – ISPE Manchester 2003 Source: Gold Sheet Jan 2009

3. Where are the Opportunities? 10% 15% 50% 25% “Follow the Money”

4. Industry Oil Refining Bulk Chemicals Fine Chemicals Pharmaceuticals Mass Productivity, Kg Product/Kg Total ex H2O >90% 20 – 50% 2 – 20% 1 – 4% How Does Pharma Compare to Others? Source: Raymond H Scherzer, Senior Vice President, Engineering, Technology & Capital Management GSK

5. 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

6. 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?

7. The 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)

8. Vision Resources Skills Incentives Action Plan Confusion Resources Skills Incentives Action Plan Frustration Vision Skills Incentives Action Plan Anxiety Vision Resources Incentives Action Plan No Change Vision Resources Skills Action Plan False Start Vision Resources Skills Incentives Steps To Successful Change Change

9. Vision Resources Skills Incentives Action Plan The Vision - Progress August 2002 • 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) 2003 September 2004 November 2005 January 2006 In Progress Change

10. Vision Resources Skills Incentives Action Plan The Vision - Challenges • 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”? Change

11. Vision Resources Skills Incentives Action Plan 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 Change

12. Vision Resources Skills Incentives Action Plan Resources - 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 Change

13. Vision Resources Skills Incentives Action Plan Resources - 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) Change

14. Vision Resources Skills Incentives Action Plan 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 Change

15. Vision Resources Skills Incentives Action Plan Skills - 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 Change

16. Vision Resources Skills Incentives Action Plan Skills - 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 Change

17. Vision Resources Skills Incentives Action Plan 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 Change

18. Vision Resources Skills Incentives Action Plan Incentives - 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? Change

19. Vision Resources Skills Action Plan Incentives Pilot / ClinicalManufacturing Risk? Bulk Manufacturing Final Dose Development Research Risk? Risk? Risk? Incentives - Challenges Risks on the Path from Molecules to Medicine Challenges Knowledge Transfer … Quality … Regulatory Compliance … Commercialization Change

20. Vision Resources Skills Action Plan Incentives Research Incentives - Challenges Risks on the Path from Molecules to Medicine Reaction, Repeatability, Scale Up, Knowledge Transfer Development Reaction, Repeatability, Scale Up, Manufacturability, Knowledge Transfer, Purification Process, Formulation Pilot / ClinicalManufacturing Development Reaction, Repeatability, Scale Up, Manufacturability, Knowledge Transfer, Purification Process, Critical Process Parameters, Best Cost Producer Bulk Manufacturing Pilot / ClinicalManufacturing Formulation, Repeatability, Scale Up, Manufacturability, Knowledge Transfer, Critical Process Parameters, Best Cost Producer Pilot / ClinicalManufacturing Final Dose Risks increase and change over time Change

21. Vision Resources Skills Incentives Action Plan Incentives - Challenges • 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 Change

22. Vision Resources Skills Incentives Action Plan 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! Change

23. Vision Resources Skills Incentives Action Plan Action 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 Change

24. Vision Resources Skills Incentives Action Plan Action 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? Change

25. Vision Resources Skills Incentives Action Plan 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! Change

26. Vision Resources Skills Incentives Action Plan Action Plan – Addressing the ChallengesEmerson and Life Sciences Quality Parameter Prediction • 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 Fault Detection Root Cause Change

27. Vision Resources Skills Incentives Action Plan Confusion Resources Skills Incentives Action Plan Frustration Vision Skills Incentives Action Plan Anxiety Vision Resources Incentives Action Plan No Change Vision Resources Skills Action Plan False Start Vision Resources Skills Incentives Steps To Successful Change Change Will We Change???

28. Vision Resources Skills Incentives Action Plan Summary • 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