Pat Manufacturing

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PAT, Manufacturing Science, QbD: Three Years After Introduction….What Are The Expectations? : 

PAT, Manufacturing Science, QbD: Three Years After Introduction….What Are The Expectations? G.K. Raju, Ph.D. Light Pharma Inc. September 2006

Outline : 

Outline BACKGROUND A FRAMEWORK CURRENT MOMENTUM EXPECTATIONS NEXT STEPS

Pharmaceutical Manufacturing : 

Pharmaceutical Manufacturing Research Development Manufacturing Marketing

Pharmaceutical Manufacturing : 

ACTIVE FORMULN FILL PACK ACTIVE FORMULN FILL PACK ACTIVE FORMULN FILL PACK RESEARCH DEVELOPMENT MANUFACTURING TIME SPACE COST QUALITY TIME SAFETY Pharmaceutical Manufacturing

FDA WARNING LETTERSTo Brand Drug Manufacturers : 

FDA WARNING LETTERSTo Brand Drug Manufacturers Abbott Laboratories AstraZeneca Aventis Baxter Healthcare Bayer Corporation Boehringer Ingelheim Bristol-Myers Squibb Eli Lilly Glaxo SmithKline Hoffmann-LaRoche Johnson and Johnson Merck & Company Novartis Pharmaceuticals Pfizer Pharmacia Schering

The Wall Street Journal: September 3rd 2003New Prescription For Drug Makers: Update the Plants : 

The Wall Street Journal: September 3rd 2003New Prescription For Drug Makers: Update the Plants “Janet Woodcock was among the architects of an FDA Crackdown under which the agency fined drug makers as much as $500 million for manufacturing failures in recent years. Yet “we still weren’t seeing acceptable levels of quality, ” she says because “manufacturing techniques were outmoded. Just refining procedures and documentation wasn’t going to change that.” -- Wall Street Journal, Sept 3rd 2003

Pharmaceutical Manufacturing : 

Research Development Manufacturing Marketing ???? Pharmaceutical Manufacturing

PHARMACEUTICAL MANUFACTURING:A Social Capability : 

PHARMACEUTICAL MANUFACTURING:A Social Capability

BACKGROUND:NOT Quality By Design : 

BACKGROUND:NOT Quality By Design

Outline : 

Outline BACKGROUND A FRAMEWORK CURRENT MOMENTUM EXPECTATIONS NEXT STEPS

FRAMEWORK:A. Science B. System C. Capability : 

FRAMEWORK:A. Science B. System C. Capability Mfg Science C. Manufacturing Capability (Robustness) PERFORMANCE Cost, Quality, Time B. Manufacturing System LEVERAGES New Products (Strategic) Existing Products (Tactical) A. Manufacturing Science

A. Manufacturing ScienceCurrent State vs. Desired State : 

A. Manufacturing ScienceCurrent State vs. Desired State Mfg. Science LEVEL 1 LEVEL 2 LEVEL 4 LEVEL 5 LEVEL 3 CORRELATIVE KNOWLEDGE What Is Correlated to What? “CAUSAL" KNOWLEDGE What “Causes” What? MECHANISTIC KNOWLEDGE How? First Principles Why? DESCRIPTIVE KNOWLEDGE: What? “There” “Here”

FRAMEWORK:A. Science B. System C. Capability : 

FRAMEWORK:A. Science B. System C. Capability Mfg Science C. Manufacturing Capability (Robustness) PERFORMANCE Cost, Quality, Time B. Manufacturing System LEVERAGES New Products (Strategic) Existing Products (Tactical) A. Manufacturing Science

B. Manufacturing SystemCurrent State vs. Desired State : 

B. Manufacturing SystemCurrent State vs. Desired State

FRAMEWORK:A. Science B. System C. Capability : 

FRAMEWORK:A. Science B. System C. Capability Mfg Science C. Manufacturing Capability (Robustness) PERFORMANCE Cost, Quality, Time B. Manufacturing System LEVERAGES New Products (Strategic) Existing Products (Tactical) A. Manufacturing Science

Outline : 

Outline BACKGROUND A FRAMEWORK CURRENT MOMENTUM EXPECTATIONS NEXT STEPS

FRAMEWORK:A. Science B. System C. Capability : 

FRAMEWORK:A. Science B. System C. Capability Mfg Science C. Manufacturing Capability (Robustness) PERFORMANCE Cost, Quality, Time B. Manufacturing System LEVERAGES New Products (Strategic) Existing Products (Tactical) A. Manufacturing Science

A. Manufacturing ScienceCurrent State vs. Desired State : 

A. Manufacturing ScienceCurrent State vs. Desired State Mfg. Science LEVEL 1 LEVEL 2 LEVEL 4 LEVEL 5 LEVEL 3 CORRELATIVE KNOWLEDGE What Is Correlated to What? “CAUSAL" KNOWLEDGE What “Causes” What? MECHANISTIC KNOWLEDGE How? First Principles Why? DESCRIPTIVE KNOWLEDGE: What? “There” “Here”

A. MANUFACTURING SCIENCEConsortia: Facilitating Discussion and Knowledge Creation : 

A. MANUFACTURING SCIENCEConsortia: Facilitating Discussion and Knowledge Creation ACTIVE FORMULN FILL PACK ACTIVE FORMULN FILL PACK ACTIVE FORMULN FILL PACK RESEARCH DEVELOPMENT MANUFACTURING e.g. CAMP ERC Govt VP Development VP Operations Regulatory FDA Scientist FDA Applied Scientist FDA Policy Makers FDA Inspector

A. MANUFACTURING SCIENCEConsortia: Facilitating Discussion and Knowledge Creation : 

A. MANUFACTURING SCIENCEConsortia: Facilitating Discussion and Knowledge Creation ACTIVE FORMULN FILL PACK ACTIVE FORMULN FILL PACK ACTIVE FORMULN FILL PACK RESEARCH DEVELOPMENT MANUFACTURING e.g. CAMP Other Govt VP Development VP Operations Regulatory FDA Scientist FDA Applied Scientist FDA Policy Makers FDA Inspector

A. MANUFACTURING SCIENCE : 

A. MANUFACTURING SCIENCE Consortia Industry, Academia Industry Development, Manufacturing Academia Pharmaceutical Engineering Regulatory Office of Testing and Research ONDQA

FRAMEWORK:A. Science B. System C. Capability : 

FRAMEWORK:A. Science B. System C. Capability Mfg Science C. Manufacturing Capability (Robustness) PERFORMANCE Cost, Quality, Time B. Manufacturing System LEVERAGES New Products (Strategic) Existing Products (Tactical) A. Manufacturing Science

B. Manufacturing SystemCurrent State vs. Desired State : 

B. Manufacturing SystemCurrent State vs. Desired State

B. Manufacturing SystemTransformations : 

B. Manufacturing SystemTransformations Wyeth Research Dominic Ventura, Parimal Desai Bristol Myers Squibb Robert Lipper, San Kiang GlaxoSmithKline Gordon Muirhead Novartis James Cheney

Manufacturing System:Regulatory Interactions : 

Manufacturing System:Regulatory Interactions NDA Submission NDA Approval Office of Compliance CMC Submissions Supplements Annual Reports PreApproval Inspections Compliance Inspections Office Of Biotechnology Products Office Of New Drug Quality Assurance US Food and Drug Administration Office Of The Commissioner Office Of Generic Drugs Office Of Testing &Research

DESIGN SPACEWhich One and When? : 

DESIGN SPACEWhich One and When? Clinical Performance Critical Quality Attributes Process Materials Controls API Attributes Impurities 1. Cmax AUC Description Identity Assay CU Impurity Dissolution 2. 3. Parameters

FRAMEWORK:A. Science B. System C. Capability : 

FRAMEWORK:A. Science B. System C. Capability Mfg Science C. Manufacturing Capability (Robustness) PERFORMANCE Cost, Quality, Time B. Manufacturing System LEVERAGES New Products (Strategic) Existing Products (Tactical) A. Manufacturing Science

C. Manufacturing Capability : 

C. Manufacturing Capability Pfizer Others…

Outline : 

Outline BACKGROUND A FRAMEWORK CURRENT MOMENTUM EXPECTATIONS NEXT STEPS

Pharmaceutical Manufacturing: An Inside-Out View That Enables A Systems View : 

Pharmaceutical Manufacturing: An Inside-Out View That Enables A Systems View

QbD At Social Level:Social Economic Consequences : 

QbD At Social Level:Social Economic Consequences TODAY

Expectations : 

Expectations Social Discussion and Knowledge Creation Will Continue Regulatory Flexibility Will Continue and Expand Individual Champions Can Build On Early Success We will get help from the “outside” Economic Benefits May Begin To Gain Momentum

NEXT THREE YEARSWhat I Hope to See More Of : 

NEXT THREE YEARSWhat I Hope to See More Of More Product Based Performance Measure Driven Real Design Space involving Clinical During Commercial Manufacturing CEO Involvement Much Larger Social Investment Closer Connectivity Between Review and Inspection

Outline : 

Outline BACKGROUND A FRAMEWORK CURRENT MOMENTUM EXPECTATIONS NEXT STEPS

FRAMEWORK:A. Science B. System C. Capability : 

FRAMEWORK:A. Science B. System C. Capability Mfg Science C. Manufacturing Capability (Robustness) PERFORMANCE Cost, Quality, Time B. Manufacturing System LEVERAGES New Products (Strategic) Existing Products (Tactical) A. Manufacturing Science

NEXT STEPS : 

NEXT STEPS “We must be the changes we wish to see in the world.” – Mahatma Gandhi