# Presentation: 925386

## PHARMACEUTICAL MANUFACTURING 

**FDA Manufacturing Subcommittee Meeting**
**July 20, 2004 **
***G.K. Raju, Ph.D.***
***Executive Director, MIT/PHARMI***
***Massachusetts Institute of Technology***

**PHARMACEUTICAL MANUFACTURING **
**IN THE 21****st**** CENTURY:**
***A “Science” Perspective***

## OUTLINE

**OUTLINE**

** ****THE “FRAME”**
** ****A VOCABULATORY**
** ****THE DESIRED STATE: ****“THERE”**
** ****THE CURRENT STATE: ****“HERE”**
** ****FROM “HERE” TO “THERE”: ****LEVERAGES**
** ****IMPLICATIONS**
** ****NEXT STEPS**
** ****ACKNOWLEDGEMENTS**

## Pharmaceutical Manufacturing:

***A Social Capability***

## OUTLINE

**OUTLINE**

** ****INTRODUCTION**
** ****A “SCIENCE” PERSPECTIVE**
** ****THE DESIRED STATE: ****“THERE”**
** ****THE CURRENT STATE: ****“HERE”**
** ****FROM “HERE” TO “THERE”: ****LEVERAGES**
** ****IMPLICATIONS**
** ****NEXT STEPS**
** ****ACKNOWLEDGEMENTS**

## “MANUFACTURING SCIENCE” :

**“****MANUFACTURING SCIENCE” :**

*** ******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?***

## A Science Perspective:1.  “SCIENCE” 

*** “******Science” (noun)***

***A body of knowledge, body of facts or information, body of laws or principles, body of truths,  or verities or realities......***

*** “******Science” (a process)***

***A means for solving problems...***

## A “Science” Perspective:2. MANUFACTURING “SYSTEM”

**A “Science” Perspective:****2. MANUFACTURING “SYSTEM”**

*A “manufacturing system” is a set of processes and systems (and people) bound by a common material and information flow.*

## A “Science” Perspective:3.  Manufacturing “Capability”

**A “Science” Perspective:****3.****  *****Manufacturing “Capability”***

**Voice of Your Customer**

**Voice Of Your Process**

**Manufacturing**
**Capability**

**=**

- CEO

- Scientist

- VP Operations

- Regulator

- Patient

## OUTLINE

**OUTLINE**

** ****INTRODUCTION**
** ****A “SCIENCE” PERSPECTIVE**
** ****THE DESIRED STATE: ****“THERE”**
** ****THE CURRENT STATE: ****“HERE”**
** ****FROM “HERE” TO “THERE”: ****LEVERAGES**
** ****IMPLICATIONS**
** ****NEXT STEPS**
** ****ACKNOWLEDGEMENTS**

## “MANUFACTURING SCIENCE” : Desired State (“There”)

**“****MANUFACTURING SCIENCE” :**** *****Desired State (“There”)***

***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?***

## “PROCESS UNDERSTANDING”:THE DESIRED STATE

***Process***
***Understanding***

***Time***

**LEVEL **
**1**

**LEVEL **
**2**

**LEVEL **
**4**

**LEVEL **
**5**

**LEVEL **
**3**

***FDA Minimum Requirement***

***Manufacturing Centric ***
***Approach to ***
***Manufacturing Science***
***(“learning by doing”)***

***Design/Development***
*** ******Centric Approach***
***Manufacturing Science***
***(“learning before doing”)***

***Launch***

## OUTLINE

**OUTLINE**

** ****INTRODUCTION**
** ****A “SCIENCE” PERSPECTIVE**
** ****THE DESIRED STATE: ****“THERE”**
** ****THE CURRENT STATE: ****“HERE”**
** ****FROM “HERE” TO “THERE”: ****LEVERAGES**
** ****IMPLICATIONS**
** ****NEXT STEPS**
** ****ACKNOWLEDGEMENTS**

## “MANUFACTURING SCIENCE” : Current State (“Here”)

**“****MANUFACTURING SCIENCE” :**** *****Current State (“Here”)***

***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?***

## “PROCESS UNDERSTANDING”:THE CURRENT STATE (“HERE”)

***Time***

**“****PROCESS UNDERSTANDING”:****THE CURRENT STATE (“HERE”)**

## OUTLINE

**OUTLINE**

** ****INTRODUCTION**
** ****A “SCIENCE” PERSPECTIVE**
** ****THE DESIRED STATE: ****“THERE”**
** ****THE CURRENT STATE: ****“HERE”**
** ****FROM “HERE” TO “THERE”: ****LEVERAGES**
** ****IMPLICATIONS**
** ****NEXT STEPS**
** ****ACKNOWLEDGEMENTS**

## FROM “HERE” TO “THERE”:STRATEGIC LEVERAGE 

**FROM ****“HERE”**** TO ****“THERE”****:*****STRATEGIC LEVERAGE ***

***Time***

**LEVEL **
**1**

**LEVEL **
**2**

**LEVEL**
** ****4**

**LEVEL **
**5**

**LEVEL **
**3**

***FDA Minimum Requirement***

***Process***
***Understanding***

***What is “development”?***
***Vocabulary?***
***How do you measure?***
***Knowledge to understanding***

## FROM “HERE” TO “THERE”:TACTICAL LEVERAGE 

**FROM ****“HERE”**** TO ****“THERE”****:*****TACTICAL LEVERAGE ***

***Time***

**LEVEL **
**1**

**LEVEL **
**2**

**LEVEL**
** ****4**

**LEVEL **
**5**

**LEVEL **
**3**

***FDA Minimum Requirement***

***Process***
***Understanding***

***Investigations***
***True Root Causes***
***Separate Critical From ***
***Non-critical***

## OUTLINE

**OUTLINE**

** ****INTRODUCTION**
** ****A “SCIENCE” PERSPECTIVE**
** ****THE DESIRED STATE: ****“THERE”**
** ****THE CURRENT STATE: ****“HERE”**
** ****FROM “HERE” TO “THERE”: ****LEVERAGES**
** ****IMPLICATIONS**
** ****NEXT STEPS**
** ****ACKNOWLEDGEMENTS**

##  Finally, A Positive Vision .....

**IMPLICATIONS****  **

*** ******Finally, A Positive Vision .....***
*** ******Enabling Vocabulary***

## “SCIENCE” PERSPECTIVE: IMPLICATIONS 3. Basis For VERY Different Relationship With Regulator

##  cGMPS FOR 21st CENTURY
 Science Based
 Risk Based
 Modern Quality Management Techniques
 Harmonization
 PAT – A FRAMEWORK FOR INNOVATIVE PHARMACEUTICAL MANUFACTURING AND QUALITY ASSURANCE

** ****Science Based**
** ****Risk Based**
** ****Modern Quality Management Techniques**
** ****Harmonization**
** ****PAT – A FRAMEWORK FOR INNOVATIVE PHARMACEUTICAL MANUFACTURING AND QUALITY ASSURANCE**

**“****SCIENCE” PERSPECTIVE: IMPLICATIONS**** *****4. Connectivity to Current Momentum***

## “SCIENCE” PERSPECTIVE: IMPLICATIONS 5.  A Basis To Collaborate With Your “Competitor”

***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?***

## “SCIENCE” PERSPECTIVE: IMPLICATIONS

***6.  An Inside-Out View That Enables A Systems View***

## “SCIENCE” PERSPECTIVE: IMPLICATIONS 7.  A Foundation To Transform Lives All Over Again..

**“****SCIENCE” PERSPECTIVE: IMPLICATIONS**** *****7.  A Foundation To Transform Lives All Over Again..***

- Time

- 1978

- 1988

- 2008

- 1998

- 2018

- 2003

- 1983

- 1993

- 2013

- 2023

- Last 25

- Years

- 2028

- Next 25

- Years

- 1978

- 1988

- 2008

- 1998

- 2018

- 2003

- 1983

- 1993

- 2013

- 2023

- Last 25

- Years

- 2028

- Next 25

- Years

***A New***

***Shared Vision***

**Manufacturing**

**Capability**

## “Science” Perspective:7.  A Foundation To Transform Lives All Over Again

**“****Science” Perspective:****7.****  *****A Foundation To Transform Lives All Over Again***

## OUTLINE

**OUTLINE**

** ****INTRODUCTION**
** ****A “SCIENCE” PERSPECTIVE**
** ****THE DESIRED STATE: ****“THERE”**
** ****THE CURRENT STATE: ****“HERE”**
** ****FROM “HERE” TO “THERE”: ****LEVERAGES**
** ****IMPLICATIONS**
** ****NEXT STEPS**
** ****ACKNOWLEDGEMENTS**

## NEXT STEPS

** ****Broaden Shared Vision **
** ****Long Term Social Roadmap**
** ****A “Real” Economic Case**
**“****Real” Case Studies**
** “****Pilot” The Future**

## OUTLINE

**OUTLINE**

** ****INTRODUCTION**
** ****A “SCIENCE” PERSPECTIVE**
** ****THE DESIRED STATE: ****“THERE”**
** ****THE CURRENT STATE: ****“HERE”**
** ****FROM “HERE” TO “THERE”: ****LEVERAGES**
** ****IMPLICATIONS**
** ****NEXT STEPS**
** ****ACKNOWLEDGEMENTS**

## ACKNOWLEDGEMENTS

**Consortium For The Advancement Of Manufacturing Of Pharmaceuticals (CAMP)**
**Charles Cooney (MIT)**
**Steve Byrn and Kenneth Morris (PURDUE)**
**Janet Woodcock, Helen Winkle and Ajaz Hussain (FDA)**