# Presentation: 080933

## MANUFACTURING SCIENCE:

**MANUFACTURING SCIENCE:**
***The Means To GMPs In the 21******st****** Century..***

**G.K.Raju, Ph.D.**

## OUTLINE

**OUTLINE**

**“****MANUFACTURING SCIENCE”: ****A DEFINITION**
**“****MANUFACTURING SCIENCE”: ****DIMENSIONS**
**MANUFACTURING SYSTEM: ****“HERE”**
**MANUFACTURING SYSTEM: ****TO ****“THERE”**
**IMPLICATIONS**

## “MANUFACTURING”

** “*****Manufacturing*****” (derived from Latin)**
**        ****= “*****manus*****” (hand) +  “*****factus*****” (made)**
**        ****= “****made by hand****”**
** “****Manufacturing” is the transformation of materials and information  into goods for the satisfaction of human needs**

*Material*

*Material*

*Information*

*Information*

## “SCIENCE”

*** ******A body of knowledge, body of facts or information, body of laws or principles, body of truths, or verities or realities......***
*** ******Skill, expertise, mastery, know-how***
*** ******Organized knowledge***
*** ******A means of solving problems..***

*The Synonym Finder*
- J. I. Rodale

## “MANUFACTURING SCIENCE”

***“******Manufacturing”***

***“******Science”***

***“ ******Manufacturing Science”***

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

***Transformation of ***
***materials and information  ***
***into goods for the ***
***satisfaction of ***
***human needs***

## “MANUFACTURING SCIENCE”:A DEFINITION

***Body of Knowledge, Laws, Principles***
***Involved In The Transformation of ***
***Materials and Information  ***
***into Goods for the ***
***Satisfaction of Human Needs***

## OUTLINE

**OUTLINE**

**“****MANUFACTURING SCIENCE”: ****A DEFINITION**
**“****MANUFACTURING SCIENCE”: ****DIMENSIONS**
**MANUFACTURING SYSTEM: ****“HERE”**
**MANUFACTURING SYSTEM: ****TO ****“THERE”**
**IMPLICATIONS**

## “MANUFACTURING SCIENCE”:DIMENSIONS

**“****MANUFACTURING SCIENCE”:****DIMENSIONS**

***Body of ***
***Knowledge, Laws, Principles***
***Involved In The Transformation of ***
***Materials and Information  into Goods ***
***for the Satisfaction of Human Needs***

***Extent***
***Of ***
***Mfg.***
***Science***

## “MANUFACTURING SCIENCE” : Levels of Knowledge

***Extent***
***Of ***
***Mfg.***
***Science***

**PROCESS KNOWLEDGE**
**How, Correlative ..**

**CAUSAL KNOWLEDGE**
**Why?**

**MECHANISTIC**
**KNOWLEDGE**

**First**
**Principles**

**DESCRIPTIVE KNOWLEDGE: **
**What, Etc, ...**

## “MANUFACTURING SCIENCE”: DIMENSIONS

**“****MANUFACTURING SCIENCE”:**** ****DIMENSIONS**

***Body of ***
***Knowledge, Laws, Principles***
***Involved In The Transformation of ***
***Materials and Information  into Goods ***
***for the Satisfaction of Human Needs***

***Extent***
***Of ***
***Mfg.***
***Science***

## “MANUFACTURING SCIENCE”:The “Time” DimensionTHE DESIRED STATE

**“****MANUFACTURING SCIENCE”:*****The “Time” Dimension*****THE DESIRED STATE**

***Extent***
***Of ***
***Mfg.***
***Science***

***Time***

***“******Right First 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”)***

## “MANUFACTURING SCIENCE”: DESIRED RELATIVE TO CURRENT STATE(Personal Opinion)

**“****MANUFACTURING SCIENCE”:***** DESIRED****** RELATIVE TO ******CURRENT****** STATE******(Personal Opinion)***

***Extent***
***Of ***
***Mfg.***
***Science***

***Time***

***“******Right First 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”)***

## OUTLINE

**OUTLINE**

**“****MANUFACTURING SCIENCE”: ****A DEFINITION**
**“****MANUFACTURING SCIENCE”: ****DIMENSIONS**
**MANUFACTURING SYSTEM: ****“HERE”**
**MANUFACTURING SYSTEM: ****TO ****“THERE”**
**IMPLICATIONS**

## “MANUFACTURING SYSTEM”

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

*Material*

*Material*

*Information*

*Information*

## MANUFACTURING SYSTEM 

** ****ACTIVE**

**      ****FORMULN**

**FILL**

**PACK**

** ****ACTIVE**

**      ****FORMULN**

**FILL**

**PACK**

** ****ACTIVE**

**      ****FORMULN**

**FILL**

**PACK**

_**RESEARCH**_

_**DEVELOPMENT**_

_**MANUFACTURING**_

**TIME**

**SPACE**

**PHARMACEUTICAL **
**MANUFACTURING SYSTEM**** **

**COST**

**QUALITY**

**TIME**

**SAFETY**

## PROCESS A WITH QC TESTS

**PROCESS A ****WITH QC TESTS**

** ****WEIGHING**

**           ****WET**
**GRANULATION**

**STEP**

**FB DRY**

**   ****STEP**

**BLEND**

**  ****ENCAPSULATE**

**SIEVE**

** ****API**
** ****MICRO**

** ****Particle Size**

** ****Description**
** ****ID**
** ****Assay**
** ****CU**
** ****Impurity**
** ****Dissolution**
** ****MICRO**

**QC****1**

**QC****3**

**QC****4**

**DRY MIX**

**QC****2**

** ****LOD**

## OUTLINE

**OUTLINE**

**“****MANUFACTURING SCIENCE”: ****A DEFINITION**
**“****MANUFACTURING SCIENCE”: ****DIMENSIONS**
**MANUFACTURING SYSTEM: ****“HERE”**
**MANUFACTURING SYSTEM: ****TO ****“THERE”**
**IMPLICATIONS**

## “MANUFACTURING SCIENCE” : Levels and Focus

***Extent***
***Of ***
***Mfg.***
***Science***

**PROCESS KNOWLEDGE**
**How, Correlative ..**

**CAUSAL KNOWLEDGE**
**Why?**

**MECHANISTIC**
**KNOWLEDGE**

**First**
**Principles**

**DESCRIPTIVE KNOWLEDGE: **
**What, Etc, ...**

## “MANUFACTURING SCIENCE”: DESIRED RELATIVE TO CURRENT STATE(Personal Opinion)

**“****MANUFACTURING SCIENCE”:***** DESIRED****** RELATIVE TO ******CURRENT****** STATE******(Personal Opinion)***

***Extent***
***Of ***
***Mfg.***
***Science***

***Time***

***“******Right First 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”)***

## OUTLINE

**OUTLINE**

**“****MANUFACTURING SCIENCE”: ****A DEFINITION**
**“****MANUFACTURING SCIENCE”: ****DIMENSIONS**
**MANUFACTURING SYSTEM: ****“HERE”**
**MANUFACTURING SYSTEM: ****TO ****“THERE”**
**IMPLICATIONS**

## Food & Drug Administration: August 21st 2002

*The FDA Announced today that the Agency will be undertaking a*
*Significant new initiative concerning the regulation of pharmaceutical*
*Manufacturing and product quality.   *
*The initiative, ****Pharmaceutical cGMPs for the 21******st****** Century: ***
***A Risk Based Approach...***
- 		-- Lester Crawford
- 		    FDA Deputy Commissioner

- _Pharmaceutical cGMPs Initiative_

## US FDAcGMPs FOR THE 21st CENTURY

** ****Science Based**
** ****Risk Based**
** ****Modern Quality Management Techniques**
** ****Harmonization**

## U.S. FDAcGMPs FOR THE 21st CENTURY

**U.S. FDA****cGMPs FOR THE 21****st**** CENTURY**

** ****Science Based**
** ****Risk Based**
** ****Modern Quality Management Techniques**
** ****Harmonization**

## PROCESS A WITH QC TESTS

**PROCESS A ****WITH QC TESTS**

** ****WEIGHING**

**           ****WET**
**GRANULATION**

**STEP**

**FB DRY**

**   ****STEP**

**BLEND**

**  ****ENCAPSULATE**

**SIEVE**

** ****API**
** ****MICRO**

** ****Particle Size**

** ****Description**
** ****ID**
** ****Assay**
** ****CU**
** ****Impurity**
** ****Dissolution**
** ****MICRO**

**QC****1**

**QC****3**

**QC****4**

**DRY MIX**

**QC****2**

** ****LOD**

## FDA  PAT Initiative

***The FDA ******Process Analytical Technologies (PAT) Initiative****** Is An Effort To Facilitate The Introduction of New Technologies To The Manufacturing Sector Of The Pharmaceutical Industry***

## CYCLE TIME COMPONENTS

**CYCLE TIME COMPONENTS**

## ON-LINE TECHNOLOGY IMPACTSDOMINANT CYCLE TIMES

**ON-LINE TECHNOLOGY IMPACTS****DOMINANT CYCLE TIMES**

**On-line LIF, NIR, Pattern Recognition, etc.**

## PHARMACEUTICAL MANUFACTURING:The PAT Opportunity..

** ****ACTIVE**

**      ****FORMULN**

**FILL**

**PACK**

** ****ACTIVE**

**      ****FORMULN**

**FILL**

**PACK**

** ****ACTIVE**

**      ****FORMULN**

**FILL**

**PACK**

_**RESEARCH**_

_**DEVELOPMENT**_

_**MANUFACTURING**_

**TIME**

**SPACE**

_**Which Products?**_**High Volume****Complex****Liquid**

***Blending***
***Drying***
***Granulation***

***Flow***
***Tableting***
***Transport***

***Assay***
***Fermentation***

***Rapid ***
***Microbial***
***Detection***

**PHARMACEUTICAL MANUFACTURING:*****The PAT Opportunity..***

## U.S. FDAcGMPs FOR THE 21st CENTURY

**U.S. FDA****cGMPs FOR THE 21****st**** CENTURY**

** ****Science Based**
** ****Risk Based**
** ****Modern Quality Management Techniques**
** ****Harmonization**

## “MANUFACTURING SCIENCE” : IMPLICATIONS

***Extent***
***Of ***
***Mfg.***
***Science***

**PROCESS KNOWLEDGE**
**How, Correlative ..**

**CAUSAL KNOWLEDGE**
**Why?**

**MECHANISTIC**
**KNOWLEDGE**

**First**
**Principles**

**DESCRIPTIVE KNOWLEDGE: **
**What, Etc, ...**

***FDA***

## U.S. FDAcGMPs FOR THE 21st CENTURY

**U.S. FDA****cGMPs FOR THE 21****st**** CENTURY**

** ****Science Based**
** ****Risk Based**
** ****Modern Quality Management Techniques**
** ****Harmonization**

## “MANUFACTURING SCIENCE” : Levels of Knowledge

***Extent***
***Of ***
***Mfg.***
***Science***

**PROCESS KNOWLEDGE**
**How, Correlative ..**

**CAUSAL KNOWLEDGE**
**Why?**

**MECHANISTIC**
**KNOWLEDGE**

**First**
**Principles**

**DESCRIPTIVE KNOWLEDGE: **
**What, Etc, ...**

## US FDAcGMPs FOR THE 21st CENTURY

**US FDA****cGMPs FOR THE 21****st**** CENTURY**

** ****Science Based**
** ****Risk Based**
** ****Modern Quality Management Techniques**
** ****Harmonization**

## APPROACH TO LEARNING:

**Consequences on Process Development & Commercial Production**

## “MANUFACTURING SCIENCE”: DESIRED RELATIVE TO CURRENT STATE(Personal Opinion)

**“****MANUFACTURING SCIENCE”:***** DESIRED****** RELATIVE TO ******CURRENT****** STATE******(Personal Opinion)***

***Extent***
***Of ***
***Mfg.***
***Science***

***Time***

***“******Right First 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”)***

## US FDAcGMPs FOR THE 21st CENTURY

** ****Science Based**
** ****Risk Based**
** ****Modern Quality Management Techniques**
** ****Harmonization**

## ????

**Pharmaceutical Manufacturing  **

**Research**

**Development**

**Manufacturing**

**Marketing**

**????**

## “MANUFACTURING SCIENCE” : Levels of Knowledge

***Extent***
***Of ***
***Mfg.***
***Science***

**PROCESS KNOWLEDGE**
**How, Correlative ..**

**CAUSAL KNOWLEDGE**
**Why?**

**MECHANISTIC**
**KNOWLEDGE**

**First**
**Principles**

**DESCRIPTIVE KNOWLEDGE: **
**What, Etc, ...**

## “MANUFACTURING SCIENCE” : IMPLICATIONS

***Extent***
***Of ***
***Mfg.***
***Science***

**PROCESS KNOWLEDGE**
**How, Correlative ..**

**CAUSAL KNOWLEDGE**
**Why?**

**MECHANISTIC**
**KNOWLEDGE**

**First**
**Principles**

**DESCRIPTIVE KNOWLEDGE: **
**What, Etc, ...**

***FDA***

## OUTLINE

**“****MANUFACTURING SCIENCE”: ****A DEFINITION**
**“****MANUFACTURING SCIENCE”: ****DIMENSIONS**
**MANUFACTURING SYSTEM: ****“HERE”**
**MANUFACTURING SYSTEM: ****TO ****“THERE”**
**IMPLICATIONS**

## MANUFACTURING SCIENCE:

**PHARMA**
**MANUFACTURING SCIENCE:**
***The Means To GMPs In the 21******st****** Century***

**G.K.Raju, Ph.D.**