excipient knowledge management mumbai 12 march 2015 part 1 & 2

[lsquoExcipientrsquo] Knowledge Management 2015 amp Beyond

Ajaz S Hussain PhD

Insight Advice amp Solutions LLCMaryland USA

Executive Director the National Institute for Pharmaceutical Technology amp Education

3122015 Ajaz S Hussain PhD 1

Acknowledgment

bull Thanks to Arihant Innochem Pvt Ltd for inviting me to speak and also for accepting my requests to (a) expand the program and include other speakers and (b) inviting faculty members from local schools of pharmacy

bull For me this is an opportunity to share my insights on excipients and more importantly learn something about excipient supplier ndash Pharma interactions in India

bull Arihant Innochem Pvt Ltd made the travel arrangements for my trip to Mumbai We have no other business or financial relationship They did not request to see nor did I provide an advance copy of my slides


Insights

bull Why attention to excipient knowledge management (specifically their functionality) is critical to mitigating risks (or to leverage opportunities) posed by the rapidly increasing complexity and uncertaintybull Note Knowledge management in

the context of lsquointellectual propertyrsquo is not the focus of this talk

bull In the second talk end of the day I plan to discuss how certain management practices can impact effectiveness of knowledge managementbull Note Knowledge management is

a combination of both IT and human aspects I intend to focus on lsquohuman factorsrsquo


Outline

bull Declaring my interests acknowledging experiences contributing to my current thinking

bull Current hot topics ndash lsquoexcipientsrsquo regulatory trends amp insights

bull Why attention to (excipient) knowledge management (specifically physical functionalityperformance) is critical


My interest in [lsquoexcipientsrsquo] KMacknowledging experiences contributing to my current thinking

bull Business decisions

bull Regulatory research policy amp enforcement

bull Academic research


Business decisions

bull Management responsibilitiesbull VP amp Global Head Biopharmaceutical Development Sandoz (2005-2009)

bull Developmentregulatory submission Omnitropereg Binocritreg Zarzioreg Generic Enoxaparin amp Glatiramer acetate

bull VP Next Generation Product Assessment amp CSO Philip Morris International (2009 -2012)

bull Developmentevidence qualityregulatory strategy Plant based vaccines amp assessment of products intended for tobacco harm reduction

bull President Biotechnology amp CSO Wockhardt (2012-2013)

bull Biosimilar and Complex Generic Strategy Improvement

bull AdvisoryConsulting (2013 ndash currently)

bull Mitigating risks in development of complex products Framework for effective compliance amp remediation Strengthening Culture of Quality


Regulatory research policy amp enforcement support US FDA (1995 ndash 2005)

bull Research to Policybull SUPAC BCS IVIVC hellipTopical Microbicideshellipseveral others

bull Policybull SUPAC-MR IVIVC BCS helliphellip PAT ICH FDA Lead (Quality) ndash

ldquodesired state for 21st Centuryrdquo ICH Q8 ndash 10

bull Enforcement Supportbull Expert witness for the prosecution (1995)

bull Facilitating resolution of difficult WLs linked to shortages


Knowledge to inform policy improvement


Physical Attributes Can be critical for safety efficacy and quality


July 15 2005 FDA Public Health Advisory Safety Warnings Regarding Use of Fentanyl Transdermal (Skin) Patches

Also relevant today Pattern Recognition


Preliminary illustration of a concept Going forward expect to see regulators utilize state-of ndashthe ndashart pattern recognition and modeling systems

Effective Regulatory System Importance of Process Understanding and Quality by DesignAjaz Hussain Pharmaceutical Quality Forum 3rd Symposium November 2004 Tokyo Japan

Academic research

University of Cincinnati (1989-1994)

bull Formulation designbull Several projects ndash oral topical and

transdermalbull Example Elaborating the utility of

Transcutolreg (Gattefosseacute)

bull Computer aided formulation designbull Artificial Neural Network based

lsquoexpert systemsrsquobull Example Prototype for lsquoTechnical

Service Supportrsquo (funding - Aqualon)

NIPTE (Currently)

bull NIPTErsquos Excipient Knowledge basebull Available since 2007 at

httppharmahuborg

bull The goal of this project is to share information and modeling tools to support pharmaceutical product


Prototype for lsquoTechnical Service Supportrsquo


From a lsquoDatabasersquo to a lsquoKnowledge basersquo

bull lsquoLook-up tablesrsquo to lsquoAbility to Predictrsquo

bull Ability to predict = generate hypotheses

bull Ability (simulate) ask questions - what if

NIPTE Knowledge Management


Contact Prof Hoag Univ Maryland shoagrxumarylandedu



This study was funded by the FDA-sponsored contract ldquoDevelopment of Quality by Design (QbD) Guidance Elements on Design Specifications across Scales with Stability Considerationsrdquo (contract number HHSF223200819929C)


Current hot topics ndashrsquoexcipientsrsquo regulatory trends amp insights ExcipientFest on 28-29 April 2015 in Washington Organizational Changes CDERFDA and Inspectional Trendshellip(Complex Genericshellip Continuous Manufacturing)


Current experience with lsquoSupplier Qualificationrsquo

bull Recent observations are summarized in this report by ECA Academy (21012015) Areas of attention

bull Accuracy and completeness of administrative documentation

bull Evidence to justify excipient and supplier qualification

bull Risk-assessment and effective integration within in QMS

bull Quality agreements

bull Going forward I envision a need to emphasize a life-cycle approach (eg linking to CAPA change control)


FDArsquos Inactive Ingredient Database -statusbull Substance Registration System (SRS)

bull Generic listing vs Specific Grade listing for commonly used excipients ndashmax precedent levels

bull Listing of Mixtures

bull The UNII code confusing the National Library of Medicine yet to finalize standards for assigning UNII codes for polymers

bull Individual Grades vs Family Data

bull Legal status of the IID and FDA communications of changes to the IID

bull DMF Implications

bull Impact on ANDAs ndash lsquoDelaysrsquo amp lsquoRefuse to File Lettersrsquo



Inactive Ingredientsrsquo to lsquoExcipientsrsquo to lsquoFunctionalityrsquo Where are we in this journeylsquo

Status of lsquoSubstances In Regulatory Practicersquo

Clearly we need a global database with improved precision and accuracy of naming (and coding) to identify describe compare and link (to products and AERs)

INDs NDAs BLAs CFRrsquos Orphan Drug ApplicationsProducts that Contain Each Substance

Pharmacological ClassificationActive Moieties Related Moieties and Salts

LADMERMetabolites

Metabolic Enzymes Transporters and EffectsDrug target (therapeutic and other) type of interaction

Solubility and Permeability (BCS)Protein Binding

Impurities and Related Substance

ISO 11238 (ISO IDMP) some challenges

Both substances amp specified substances

Implementation in EU EMA Task force

Global Ingredients Archive System (GInAS)


The War Against Fake Medicines Update on FDASIA - Guidance and Impact on Excipient Suppliers and

Users QbD Sampling Guidelines The NSFIPECANSI 363 2014 GMP standardsexplained Good Supply Practices ndash Using Cross Industry Knowledge to Devise Pragmatic Solutions Impact

of Non-harmonized Standards and What is Needed to Achieve Harmonization Advancements in the Question Based Review approach and various other excipient specific related topics An Overview of the FDA OGD

IID EWG activities Effective Sourcing and Purchasing of Excipients

Industry Collaboration for Science Based Implementation of Elemental Impurities Challenges And Opportunities In Developing

And Modernizing Public Standards For NF Excipients Monographs For Regulated Drug

Products Marketed In The USA Future Pharma Manufacturing Efficiencies and the Role of Innovative Excipient Technologies

IPEC ExcipientFest 2015

Current Hot Topics ExcipientFest on 28-29 April 2015 in Washington


The War Against Fake Medicines Update on FDASIA - Guidance and Impact on Excipient

Suppliers and Users QbD Sampling Guidelines The NSFIPECANSI 363 2014 GMP standards explained Good Supply Practices ndash Using Cross Industry Knowledge to Devise

Pragmatic Solutions Impact of Non-harmonized Standards and What is Needed to Achieve

Harmonization Advancements in the Question Based Review approach and various other

excipient specific related topics An Overview of the FDA OGD IID EWG activities Effective

Sourcing and Purchasing of Excipients Industry Collaboration for Science Based Implementation of Elemental Impurities Challenges And

Opportunities In Developing And Modernizing Public Standards For NF ExcipientsMonographs For Regulated Drug Products Marketed In The USA Future Pharma Manufacturing Efficiencies and the Role of Innovative Excipient Technologies


Inspectional trends in data integrity (Bangalore Nov

2014)

22(d)

192

100(a)

160(b)

110(a)

67(b)

68(a)

25(a)

67(a)

100(b)

Recurring 483 Observations Top 10

22(d) 192 100(a) 160(b)110(a) 67(b) 68(a) 25(a)67(a) 100(b)

Jeff Medwid NIPTE-FDA Conference 13 June 2012

International Society for Pharmaceutical Engineering (ISPE) in conjunction with McKinsey amp Co will release preliminary data and findings from its Quality Metrics Pilot Program at the ISPE Quality Metrics Summit on April 21ndash22 in Baltimore

FDA Launches New Drug Quality Office With Goal of Improving the Pharmaceutical IndustryPosted 13 January 2015By Alexander Gaffney RAC

FDArsquos New Pharma Quality

Office Will Take a Team Approach

Yu Explains

Regulatory Recon Investigations Find Major Quality Problems at Indian Pharma Companies (3 December 2014)Posted 03 December 2014By Alexander Gaffney RAC

Currently the environment is complex there is high uncertainty D

on

rsquot f

org

et

fun

ctio

na

lity

o

f e

xcip

ien

ts i

s im

po

rta

nt


Need for urgent progress lsquoInactive Ingredientsrsquo to lsquoExcipientsrsquo to lsquoFunctional Excipientsrsquo

Importance of assuring quality and controlling

variability of excipients

including their lsquofunctionalityrsquo has

long been recognized

bull Increasing complexity of drugs their delivery and failure modes

bull Patient (eg pediatric) relevant failure modes

bull Simple generics to complex generics amp biosimilars

Urgent need to address gaps in the FDArsquos Inactive Ingredient Database


Trends Lab amp Manufacturing

ldquoDeletion of Datardquo

ldquoTesting Into Compliancerdquo

ldquoBMR manipulation is a slippery sloperdquo

ldquoSuggestive of faulty manufacturing process or practices even if this is not the caserdquo

ldquoIt is top managementrsquos responsibility to ensure the training program is robust and effectiverdquo

Inspectional trends in data integrity (Bangalore Nov 13 2014 - Nov 14 2014)

Growing concern some

companies ldquodata looks too good

to be truerdquo


GMP Compliance amp Remediation


QbD amp QbR Clarity on Critical Functionality


Office Will Take a Team

Approach Yu Explains

Carmelo Rosa MS PsyD November 2014

Urgent Need amp Opportunity

To align amp ensure sound scientific basis of these critical regulatory decisions

FDA CDER OPQ Plans for Surveillance of Pharmaceutical Quality

Teresa Mullin PhD December 2014


Need for a comprehensive (excipient) knowledge base



Why attention to (excipient) knowledge management is criticalSpecifically for physical attributes functionality performance



Today there are several product categories (eg controlled release inhalation products DPIrsquos topical transdermal liposomal products etc) which requires an exquisite control of complex physical material and product attributes (functionality)

Many of our current measurement systems need improvement

We depend on these to ensure control of lot-lot variability

Measurement system capability must be confirmed to be able to assess process capability (calibration amp Gauge RampR)

Life-cycle approach to quality continued process verification (FDArsquos Process Validation 2011) is a safety net

Supplier amp Excipient Qualification amp Process Validation

Measurement System Analysis

bull From lsquocalibrationrsquo to lsquoGauge RampRrsquoParticularly for physical

attributes destructive analysis

bull Many (including regulators) have not yet understood its importance

Gauge RampR well established but not commonly practiced

bull Measurement system in a state of control effective CAPA quality metrics Culture of Quality

With the move towards Statistical Process Control

bull Demonstrate equivalent in vitro performance more exacting criteria

Development of complex generic products (ER

Injectable Inhalation etc)


Process Validation (2011) Statistical Confidence Continued Process Verificationhellip


httpwwwslideshareneta2zpharmsciperformance-testing-pharmaceutical-quality-2004(accessed 6 December 2014)


Supplier amp Excipient Qualification amp CAPA

Out of Specification events are difficult to resolve

Excipient functionality can be a significant contributing factor

Sometimes reluctantly have to settle with - ldquoRoot cause unknown

600 days

I have inserted the ldquo600 daysrsquo on the figure ndash this is based on cases I have seen while at FDA)


Prevention of OOS and Effective CAPA needs a focus on critical functional attributes




Compendial standards and manufacturing


Practice Control Process Maturity

Initial

bull Unpredictable

Managed

bull Characterized but reactive

Defined

bull Characterized proactive

Measured amp Controlled

bull In control

Optimizing

bull Focus on improvement


Capability Maturity Model Integration Carnegie Mellon University

A validated process

Maturity Level amp Assurance of Quality

Managed Characterized but reactive

High perceived risk of

lsquoCheating by Designrsquo

ldquoTrial Injectionsrdquo

ldquoTesting in to Compliancerdquo

Defined Characterized proactive

Lower level of assurance

Stopping amp Correcting

Batch Rejection

Measured amp

ControlledIn control

Quality by Design

Quality Assured

Improvement Opportunities


At the individual level in QC functionndash how often does this occur

attitude toward

performing the behavior

Process validation is

done so quality is good

test prone to error

ldquoBatch failure means I made

a mistakerdquo

subjective norm

documentation not critical

Compendial testing

sufficient

Indian regulators

collect amp test samples ndash no issue there


ldquoTesting into compliancerdquo

In general ndash low empowerment is a significant challenge (low perceived behavioral control) plus reasons to rationalizehellip

Excipient Functionality Can be critical for safety efficacy and quality



A pattern of failure Pharmaceutical Equivalence by Design (2004)


httpwwwnihsgojpdrugPhForumdocuments041122Hussain041122pdf

An attempt to correct


httpipecamericasorgsystemfilesKeyNoteEF13May11LawrenceYu(FDA)pdf

Recent challenges


Th

e V

oic

e o

f th

eA

mer

ican

P

sych

iatr

ic A

sso

ciat

ion

and

th

e P

sych

iatr

ic C

om

mu

nit

y

Physicians Question FDAs Confidence in Generic Drugs Safety Efficacy (OCTOBER 24 2014)

bull ldquomost patientsrdquo is not the same asldquo all patientsrdquo and whether the 24 to 36 normal subjects used in the agencys bioequivalency tests represents the full range of individual variation in the way drugs are absorbed across the pharmaceutical using population is uncertain

bull Individuals can sometimes be allergic and react differently to whatever substance goes into making up the capsule or the tablet

FDA Flags Generic Versions of ADHD Medication(NOVEMBER 14 2014)

bull FDA changed the therapeutic equivalence (TE) rating from AB to BXmdashmeaning that the products are still approved and can be prescribed but are no longer recommended as automatic substitutes

RLD Variability Can be a block-buster opportunityFocus on lsquocontrol strategyrsquo

bull Overcoming CP amp IP provide FDA a submission they need to address CP

bull Then begin with QTPP CQArsquos hellip skip lsquodesign spacersquo and focus on lsquocontrol strategy

bull The entire development team should read the complete package insert of RLD

bull Discuss to ensure a common understandingbull Failure modes amp intended use

bull Pharmaceutical Equivalence

bull Bioequivalence

bull Other studies

QbD Challenges


NewRegulators are not prepared to handle QbD applications

NewMisalignment of international regulatory authorities

New and Generics

RampD incentivized for lsquoshots on the goalrsquo not QbD

GenericsLack of belief in business case ndash lsquoGenerics are all about file first figure out laterrsquo

Biologics Lack of technology to execute

Ted Fuhr Mackinsey amp Company June 2010 FDA Advisory Committee

Summary

bull Excipient functionality can contribute in critical ways to product quality amp performance adequate control is necessary

bull Our databases tools and knowledge are lagging behind the rapidly increasing complexity and uncertainty

bull Risk to quality and to business is increasing and regulatory transitions pose additional difficulties

bull Effective knowledge management ndash IT and Human practices ndash is critical for organizational lsquobottom-linersquo

bull We all must come together collaboratively to address the urgent needs we owe it to the patients we serve


Knowledge Management amp Culture of Quality

Ajaz S Hussain PhD





Life-cycle approach needed for knowledge management

Investigational ProductscGMPs

DevelopmentTechnology

TransferCommercial

ManufacturingDiscontinuation

Management Responsibility

Process Performance amp Product Quality Monitoring SystemCAPA Change Management Management Review

PQS Elements

Knowledge ManagementQuality Risk ManagementEnablers

ICH Q10 KM is a systematic approach to acquiring analyzing storing and disseminating information related to products manufacturing processes and components

Based on ICH Q10

ldquowe can be blind to the obvious and we are also blind to our blindnessrdquo

Daniel Kahneman Thinking Fast and Slow

3142015 Ajazajazhussaincom 45

httpwebmiteduperscipeopleadelsoncheckershadow_proofhtml


1938 The Federal Food Drug and Cosmetic (FDC)

bull 1937 Elixir of Sulfanilamide

1962 Kefauver-Harris Drug Amendments

bull 1962 Thalidomide

bull 1960 Color Additive Amendment

bull 1958 Food Additives Amendment GRAS



1992 Generic Drug Enforcement Act

bull1989 L-Tryptophan

bull 1989 Generic Drug Scandal

bull 1988 Food and Drug Administration Act

bull 1984 Fines Enhancement Laws Drug Price Competition and Patent Term Restoration Act

2012 Food and Drug Administration Safety and Innovation Act (FDASIA)

bull 2007 Heparin Disaster

2013 Pandemic and All-Hazards Preparedness Reauthorization Act (PAHPRA) Drug Quality and Security Act

bull 2012 The Deadly Meningitis Outbreak

Past 70 years 1937 ndash 2007 The diethylene glycol (DEG) narrative


0

5

10

15

20

25

30

35

Yea

rs

DEG Years since the previous incident

0

50

100

150

200

250

300

350

Number of Reported Deaths

1937

Eli

xir

of

Sulf

anil

amid

e

2007T

ootp

aste

conta

min

atio

n

0 70 years 0 70 years

Frequent reports

Mumbai Mumbai

Data from Excipient Fest Janeen Skutnik Chair ndashIPECAmericas 2009

Past 70+ years DEG contamination or economically motivated adulteration


Reported cases underestimate the real tragedy rapid intervention may not occur

Epidemic of Pediatric Deaths From Acute Renal Failure Caused by

Diethylene Glycol Poisoning JAMA 1998279(15)1175-1180

doi101001jama279151175

Month of hospital admission for children with

acute renal failure Haiti

October 1995-October 1996

Diethylene glycol poisoning in Gurgaon India 1998Bulletin of the World Health Organization 2001 79 88ndash95

We report a second episode of poisoning occurring in 1998 in

India as a result of children ingesting diethylene glycol at

least 33 children are known to have died

At the beginning of the investigation we never imagined that

contaminated medicine was causing acute renal failure in

children

A brand of cough expectorant manufactured by a local

pharmaceutical company was found by the Central Drugs

Laboratory Calcutta to contain 175 (vv) diethylene

glycol

The district and state drug controller had tested many

samples using thin layer chromatography before a sample of

medicine tested positive for diethylene glycol at the Central

Drugs Laboratory None of the earlier samples was found to

be contaminated


Guidance for Industry Testing of

Glycerin for Diethylene Glycol

CDER May 2007 Compliance

1 Manufacturers did not perform full

identity testing on the glycerin raw

material including tests to quantify

the amount of DEG

2 Relied on the certificate of analysis

(COA)

3 The origin of the glycerin was not

easily apparent from the COA

4 The COA was often a copy of a COA

on the letterhead of the distributor

5 The chain of custody or distribution

history of the glycerin was also not

readily known

USP Glycerin Monograph

Type of Posting Revision Bulletin

Posting Date 04ndashFebndash2009

Official Date 01ndashMayndash2009

Because of the serious hazards

associated withhellip and in response to

recommendations set forth in the

FDA Guidance for Industry Testing

of Glycerin for Diethylene Glycol

published in May 2007 USP has

revised the USP Glycerin monograph

Because diethylene glycol and

ethylene glycol are considered

unacceptable toxic substances the

testing of USP Glycerin should

demonstrate the absence of these

substances

April 2007 FDA request to

USP to revise the Glycerin

monographrsquos

IDENTIFICATION section

Revision includes adding ndash

Identification test B LIMIT OF

DIETHYLENE GLYCOL AND

ETHYLENE GLYCOL to detect

and quantify DEGEG in Glycerin

minus Is no longer part of the impurity

testing

ldquoLimit of DEG and Related

Compoundsrdquo minus Introduces a

capillary gas-chromatographic

(GC) method with flame ionization

detection (FID) minus Limit of NMT

010 each for diethylene glycol

and ethylene glycol is found

70+ years to get here how difficult will it be to change habits such as lsquoblind reliance of COArsquo


Personality and Habitual Frame Biases

Myers Brigs ENTJ (first tested at FDA)

S

TF

Expanded frame

future

possibilities

objective lsquocause

and effectrsquo

Expanded frame

future

possibilities

people and

relationships

Narrow frame

the present

individuals and

relationships

Narrow frame

the present

objective

cause and

effect

N

Based on Stanford Webinar - How to Overcome the Top 3 MegaBiases in Decision-Making

Stanford Universityrsquos Strategic Decision and Risk Management certificate program

From Mapping a Managers Brain on Incentives

Social

influences

Relative

thinking

UncertaintyComplexity

By Design Intention to act consciously

bull In the interest of patients and to continually improve this ability bull To provide a healing touch ndash one life at a time in what we do and how we

do it


Consciously

Scientific methodology

Engineering Design

Plan-Do-Check-Act

Subconsciously

Habits (work to get rid of bad ones)

Habits (work to cultivate good one)

Keystone habits (Safety Alcoa ALCOA of data integrity)

The Power of Habit Why We Do What We Do in Life and Business Charles Duhigg (2012)

httpwwwslideshareneta2zpharmscipharmaceutical-culture-of-quality

What does it take to come out of the cGMP crisis

Persuasive demonstration of

(1) Ability to face facts

(2) Legal amp regulatory requirements

3) Systems approach to quality

4) Changing behavior amp culture

What is often missed or is unconvincing is how you will strengthen culture of quality

ldquoLet one who wants to move and convince others first be convinced and moved themselvesrdquo Thomas Carlyle

Signals that question the competence motivation andor integrity of company personnel

Do not defend the plainly indefensible it adds further serious credibility costs


Quality is everyones responsibility

Lack of knowledge that is

the problem

If you do not know how to ask the

right question you discover nothing

If you cant describe what you

are doing as a process you dont know what youre

doing

Rational behavior requires theory

Reactive behavior requires only reflex

action

Whenever there is fear you will get wrong figures


Selected quotes W Edwards Deming


Organization (Policies amp Sr Mgmt)

Technology(Constraints amp Controls)

Individual (Training amp Certification)

Team amp Supervisor (Soft Defenses)

Defenses(Quality Management System)

Error

Latent अपरकट conditions Goal conflicts amp mixed messages

Design flaws

Production pressures

Fear of error

ldquoWE CANNOT CHANGE THE HUMAN CONDITION BUThellipWE CAN CHANGE THE CONDITIONS UNDER WHICH HUMANS WORKrdquo JAMES REASON

Disregard to Malice

3142015 copy Ajaz S Hussain | Insight Advice amp Solutions LLC 55

ldquohelliprecords not completed

contemporaneouslyrdquo

ldquohellipobserved analyst back-date logbooksrdquo

ldquohelliptrial injectionshelliprdquo

ldquohellipresults failing specifications are

retested until acceptable results are obtainedhelliprdquo

ldquohellipover-writing electronic raw datahelliprdquo

ldquohellipOOS not investigates per XYZ SOPrdquo

ldquohellipappropriate controls not establishedhelliprdquo

Each additional observation adds

reasons to confirm that this is very likely a system

with intentional lsquoholesrsquo in its

defenses

Preconditions

Rationalization amp Attitude

Pressure amp Incentive

Opportunity ndashlsquoholes in the QMSrdquo



Attitude towards the behavior

Subjective norm

Perceived behavioral

control

IntentionFuture

Behavior

usually found to predict behavioral intentions with a high degree of accuracy

intentions in combination with perceived behavioral control can account for a considerable proportion of variance in behavior

PastBehavior

Ajen I The theory of planned behavior ORGANIZATIONAL BEHAVIOR AND HUMAN DECISION PROCESSES 50 179-211 (1991)

Heparin tragedy 2007 and 2008

FDA reports 149 deaths with allergic or hypersensitivity symptoms during that period

bull Contaminated heparin from China

QC Testing

bull Initial testing failed to detect the contaminant

Pharmacovigilence

bull Signals in the pharmacovigilence systems responded slowly and

Eventually the severity of reactions associated made it likely that the contamination would be detected

bull too late for those who died or were injured


Congressman Shimkus When the drug safety system fails people get sick Some die

bull Some of these people are already very vulnerable and proving the cause of harm from impurities adulteration and counterfeits can be elusive

It is hard to detect harm

bull Certainly the companies are obligated to ensure a culture of quality and maintain vigilance as well This reflects a systems approach to safety

FDA inspectors look for a culture of quality at

manufacturing facilities

bull FDA policies led to the failure to inspect the Chinese plantThis system approach wasnt at

play here

bull While it doesnt deny the counterfeit source tries to say that counterfeits didnt cause the reaction as if the adulteration itself was no big deal Is this an acceptable mindset helliphelliphellip

This brings me to China and its quality culture or lack thereof


ONE HUNDRED TENTH CONGRESS SECOND SESSION APRIL 29 2008 Serial No 110-109

21 CFR PART 211 SUBPARTS -Deviations signal gaps in CoQ

bullGENERAL PROVISIONSA

bullORGANIZATION AND PERSONNELB

bullBUILDINGS AND FACILITIESC

bullEQUIPMENTD

bullCONTROL OF COMPONENTS AND DRUG PRODUCT CONTAINERS AND CLOSURESE

bullPRODUCTION AND PROCESS CONTROLSF

bullPACKAGING AND LABELING CONTROLG

bullHOLDING AND DISTRIBUTIONH

bullLABORATORY CONTROLSI


For example the combinationhellip


bull Scientific methodology

bull Engineering Design

bull Plan-Do-Check-ActConsciously

bull Habits (work to get rid of bad ones)

bull Habits (work to cultivate good one)

bull Keystone habits (Safety Alcoa ALCOA of data integrity)

Subconsciously


CoQ How

bull What are the predictors of CoQCoQ Manifests by Design -

lsquoquality by designrsquo the foundation

bull 1 2 3When do people change their behaviors

bull A B C D (any body can dance)What makes a QMS effective

bull X Y ZWhen proactive compliance occurs


Going beyond rules pays


Human behavior Connecting the Dots With the Right Connectors

GXPs ndash rational behaviors

How proactive compliance is achieved X Y Z

Quality Management System

What makes a QMS reliable A B C D

Culture of Quality

Why people change their behavior 1 2 3

Human Behaviors Beyond GXPs

Predictors of Culture of Quality

Why What and How of Culture of Quality

9192014 copy Ajaz S Hussain | INSIGHT ADVICE amp SOLUTIONS LLC 64

Predictors of CoQ Act consciously in the interest of patients ndash when no one is looking


Only four attributes

actually predict a culture of

quality

Leadership Emphasis

Message Credibility

Peer Involvement

Employee Empower-ment

People will change their

behavior if they see the new behavior as

Normal

(1)

Rewarding

(2)

Easy

(3)

Dr W Edwards Demingrsquos - ldquoOut of the crisisrdquo


The journey requires leadership

with Profound Knowledge as a

guide

bull As leaders responsible for system change top management is most in need of profound knowledge

bull Quality is often determined in the boardroom

bull Problems arise when management reacts to common cause or chance variation as if it were special cause variation

bull Prediction based in theory provides a foundation for planning a course of action Plan ndash Do ndash Check ndash Act

bull The leader serves the people with clear vision and guidance to empower them To be empowered is to share ownership in the identity

bull Giving people a certain degree of control over their work fulfills the need for freedom and provides opportunity for taking joy in work

Profound Knowledge as a guide


Appreciation for a System

Theory of Knowledge

Knowledge about

Variation

Human Behavior -Psychology of Change

A

B

C

D+

Systems Approach for ErrorDeviation Management







Error


Design flaws


Fear of error

Human error models and management J Reason BMJ 320 768ndash770 (2000)

D+

Culture of Error Management परबधनbull Error strain

bull Covering upFear of Errors

bull Anticipation

bull Risk takingAwareness

bull Development QbDRFT

bull Error detection Communication

bull Analyzing errors Correction

Mastery orientation


Dots amp Connections


CoQ

1

2

3

QMS

A

B

C

D

GXP Behaviors

X

Y

Z


Culture of Quality

Normal

Rewarding

Easy

QMS

System

Knowledge

Variation

Behavior

Behavior -GXPs

Fear Removed

Mastery

Awareness

EnvironmentLeadership Emphasis

Message Credibility

Peer Involvement

Employee Empowerment

Connect to CoQ

Connect to GXPs

A Framework and a Tool (for gap analysis)

Acknowledgment

bull Thanks to Arihant Innochem Pvt Ltd for inviting me to speak and also for accepting my requests to (a) expand the program and include other speakers and (b) inviting faculty members from local schools of pharmacy

bull For me this is an opportunity to share my insights on excipients and more importantly learn something about excipient supplier ndash Pharma interactions in India

bull Arihant Innochem Pvt Ltd made the travel arrangements for my trip to Mumbai We have no other business or financial relationship They did not request to see nor did I provide an advance copy of my slides


Insights






Outline










Business decisions


























Academic research








NIPTE (Currently)


httppharmahuborg









































LADMERMetabolites




























2014)

22(d)

192

100(a)

160(b)

110(a)

67(b)

68(a)

25(a)

67(a)

100(b)


22(d) 192 100(a) 160(b)110(a) 67(b) 68(a) 25(a)67(a) 100(b)






Yu Explains



on

rsquot f

org

et

fun

ctio

na

lity

o

f e

xcip

ien

ts i

s im

po

rta

nt





















to be truerdquo













































600 days










Initial

bull Unpredictable

Managed


Defined



bull In control

Optimizing




A validated process










Batch Rejection

Measured amp


Quality by Design

Quality Assured




attitude toward




test prone to error


a mistakerdquo

subjective norm


Compendial testing

sufficient

Indian regulators














Recent challenges


Th

e V

oic

e o

f th

eA

mer

ican

P

sych

iatr

ic A

sso

ciat

ion

and

th

e P

sych

iatr

ic C

om

mu

nit

y












bull Bioequivalence

bull Other studies

QbD Challenges




New and Generics





Summary








Ajaz S Hussain PhD








TransferCommercial




PQS Elements



Based on ICH Q10

























0

5

10

15

20

25

30

35

Yea

rs


0

50

100

150

200

250

300

350


1937

Eli

xir

of

Sulf

anil

amid

e

2007T

ootp

aste

conta

min

atio

n


Frequent reports

Mumbai Mumbai







doi101001jama279151175










children




glycol





be contaminated








the amount of DEG


(COA)







readily known

















substances



monographrsquos








testing












S

TF

Expanded frame

future

possibilities


and effectrsquo

Expanded frame

future

possibilities

people and

relationships

Narrow frame

the present

individuals and

relationships

Narrow frame

the present

objective

cause and

effect

N




Social

influences

Relative

thinking




do it


Consciously


Engineering Design

Plan-Do-Check-Act

Subconsciously



















the problem





doing



action










Error


Design flaws


Fear of error


Disregard to Malice














defenses

Preconditions







Subjective norm


control

IntentionFuture

Behavior



PastBehavior





QC Testing


Pharmacovigilence












play here









bullEQUIPMENTD















Subconsciously


CoQ How














Culture of Quality










quality

Leadership Emphasis

Message Credibility

Peer Involvement




Normal

(1)

Rewarding

(2)

Easy

(3)





guide










Theory of Knowledge

Knowledge about

Variation


A

B

C

D+








Error


Design flaws


Fear of error


D+



bull Anticipation





Mastery orientation




CoQ

1

2

3

QMS

A

B

C

D

GXP Behaviors

X

Y

Z


Culture of Quality

Normal

Rewarding

Easy

QMS

System

Knowledge

Variation

Behavior

Behavior -GXPs

Fear Removed

Mastery

Awareness


Message Credibility

Peer Involvement


Connect to CoQ

Connect to GXPs


Insights






Outline










Business decisions


























Academic research








NIPTE (Currently)


httppharmahuborg









































LADMERMetabolites




























2014)

22(d)

192

100(a)

160(b)

110(a)

67(b)

68(a)

25(a)

67(a)

100(b)


22(d) 192 100(a) 160(b)110(a) 67(b) 68(a) 25(a)67(a) 100(b)






Yu Explains



on

rsquot f

org

et

fun

ctio

na

lity

o

f e

xcip

ien

ts i

s im

po

rta

nt





















to be truerdquo













































600 days










Initial

bull Unpredictable

Managed


Defined



bull In control

Optimizing




A validated process










Batch Rejection

Measured amp


Quality by Design

Quality Assured




attitude toward




test prone to error


a mistakerdquo

subjective norm


Compendial testing

sufficient

Indian regulators














Recent challenges


Th

e V

oic

e o

f th

eA

mer

ican

P

sych

iatr

ic A

sso

ciat

ion

and

th

e P

sych

iatr

ic C

om

mu

nit

y












bull Bioequivalence

bull Other studies

QbD Challenges




New and Generics





Summary








Ajaz S Hussain PhD








TransferCommercial




PQS Elements



Based on ICH Q10

























0

5

10

15

20

25

30

35

Yea

rs


0

50

100

150

200

250

300

350


1937

Eli

xir

of

Sulf

anil

amid

e

2007T

ootp

aste

conta

min

atio

n


Frequent reports

Mumbai Mumbai







doi101001jama279151175










children




glycol





be contaminated








the amount of DEG


(COA)







readily known

















substances



monographrsquos








testing












S

TF

Expanded frame

future

possibilities


and effectrsquo

Expanded frame

future

possibilities

people and

relationships

Narrow frame

the present

individuals and

relationships

Narrow frame

the present

objective

cause and

effect

N




Social

influences

Relative

thinking




do it


Consciously


Engineering Design

Plan-Do-Check-Act

Subconsciously



















the problem





doing



action










Error


Design flaws


Fear of error


Disregard to Malice














defenses

Preconditions







Subjective norm


control

IntentionFuture

Behavior



PastBehavior





QC Testing


Pharmacovigilence












play here









bullEQUIPMENTD















Subconsciously


CoQ How














Culture of Quality










quality

Leadership Emphasis

Message Credibility

Peer Involvement




Normal

(1)

Rewarding

(2)

Easy

(3)





guide










Theory of Knowledge

Knowledge about

Variation


A

B

C

D+








Error


Design flaws


Fear of error


D+



bull Anticipation





Mastery orientation




CoQ

1

2

3

QMS

A

B

C

D

GXP Behaviors

X

Y

Z


Culture of Quality

Normal

Rewarding

Easy

QMS

System

Knowledge

Variation

Behavior

Behavior -GXPs

Fear Removed

Mastery

Awareness


Message Credibility

Peer Involvement


Connect to CoQ

Connect to GXPs


Outline










Business decisions


























Academic research








NIPTE (Currently)


httppharmahuborg









































LADMERMetabolites




























2014)

22(d)

192

100(a)

160(b)

110(a)

67(b)

68(a)

25(a)

67(a)

100(b)


22(d) 192 100(a) 160(b)110(a) 67(b) 68(a) 25(a)67(a) 100(b)






Yu Explains



on

rsquot f

org

et

fun

ctio

na

lity

o

f e

xcip

ien

ts i

s im

po

rta

nt





















to be truerdquo













































600 days










Initial

bull Unpredictable

Managed


Defined



bull In control

Optimizing




A validated process










Batch Rejection

Measured amp


Quality by Design

Quality Assured




attitude toward




test prone to error


a mistakerdquo

subjective norm


Compendial testing

sufficient

Indian regulators














Recent challenges


Th

e V

oic

e o

f th

eA

mer

ican

P

sych

iatr

ic A

sso

ciat

ion

and

th

e P

sych

iatr

ic C

om

mu

nit

y












bull Bioequivalence

bull Other studies

QbD Challenges




New and Generics





Summary








Ajaz S Hussain PhD








TransferCommercial




PQS Elements



Based on ICH Q10

























0

5

10

15

20

25

30

35

Yea

rs


0

50

100

150

200

250

300

350


1937

Eli

xir

of

Sulf

anil

amid

e

2007T

ootp

aste

conta

min

atio

n


Frequent reports

Mumbai Mumbai







doi101001jama279151175










children




glycol





be contaminated








the amount of DEG


(COA)







readily known

















substances



monographrsquos








testing












S

TF

Expanded frame

future

possibilities


and effectrsquo

Expanded frame

future

possibilities

people and

relationships

Narrow frame

the present

individuals and

relationships

Narrow frame

the present

objective

cause and

effect

N




Social

influences

Relative

thinking




do it


Consciously


Engineering Design

Plan-Do-Check-Act

Subconsciously



















the problem





doing



action










Error


Design flaws


Fear of error


Disregard to Malice














defenses

Preconditions







Subjective norm


control

IntentionFuture

Behavior



PastBehavior





QC Testing


Pharmacovigilence












play here









bullEQUIPMENTD















Subconsciously


CoQ How














Culture of Quality










quality

Leadership Emphasis

Message Credibility

Peer Involvement




Normal

(1)

Rewarding

(2)

Easy

(3)





guide










Theory of Knowledge

Knowledge about

Variation


A

B

C

D+








Error


Design flaws


Fear of error


D+



bull Anticipation





Mastery orientation




CoQ

1

2

3

QMS

A

B

C

D

GXP Behaviors

X

Y

Z


Culture of Quality

Normal

Rewarding

Easy

QMS

System

Knowledge

Variation

Behavior

Behavior -GXPs

Fear Removed

Mastery

Awareness


Message Credibility

Peer Involvement


Connect to CoQ

Connect to GXPs







Business decisions


























Academic research








NIPTE (Currently)


httppharmahuborg









































LADMERMetabolites




























2014)

22(d)

192

100(a)

160(b)

110(a)

67(b)

68(a)

25(a)

67(a)

100(b)


22(d) 192 100(a) 160(b)110(a) 67(b) 68(a) 25(a)67(a) 100(b)






Yu Explains



on

rsquot f

org

et

fun

ctio

na

lity

o

f e

xcip

ien

ts i

s im

po

rta

nt





















to be truerdquo













































600 days










Initial

bull Unpredictable

Managed


Defined



bull In control

Optimizing




A validated process










Batch Rejection

Measured amp


Quality by Design

Quality Assured




attitude toward




test prone to error


a mistakerdquo

subjective norm


Compendial testing

sufficient

Indian regulators














Recent challenges


Th

e V

oic

e o

f th

eA

mer

ican

P

sych

iatr

ic A

sso

ciat

ion

and

th

e P

sych

iatr

ic C

om

mu

nit

y












bull Bioequivalence

bull Other studies

QbD Challenges




New and Generics





Summary








Ajaz S Hussain PhD








TransferCommercial




PQS Elements



Based on ICH Q10

























0

5

10

15

20

25

30

35

Yea

rs


0

50

100

150

200

250

300

350


1937

Eli

xir

of

Sulf

anil

amid

e

2007T

ootp

aste

conta

min

atio

n


Frequent reports

Mumbai Mumbai







doi101001jama279151175










children




glycol





be contaminated








the amount of DEG


(COA)







readily known

















substances



monographrsquos








testing












S

TF

Expanded frame

future

possibilities


and effectrsquo

Expanded frame

future

possibilities

people and

relationships

Narrow frame

the present

individuals and

relationships

Narrow frame

the present

objective

cause and

effect

N




Social

influences

Relative

thinking




do it


Consciously


Engineering Design

Plan-Do-Check-Act

Subconsciously



















the problem





doing



action










Error


Design flaws


Fear of error


Disregard to Malice














defenses

Preconditions







Subjective norm


control

IntentionFuture

Behavior



PastBehavior





QC Testing


Pharmacovigilence












play here









bullEQUIPMENTD















Subconsciously


CoQ How














Culture of Quality










quality

Leadership Emphasis

Message Credibility

Peer Involvement




Normal

(1)

Rewarding

(2)

Easy

(3)





guide










Theory of Knowledge

Knowledge about

Variation


A

B

C

D+








Error


Design flaws


Fear of error


D+



bull Anticipation





Mastery orientation




CoQ

1

2

3

QMS

A

B

C

D

GXP Behaviors

X

Y

Z


Culture of Quality

Normal

Rewarding

Easy

QMS

System

Knowledge

Variation

Behavior

Behavior -GXPs

Fear Removed

Mastery

Awareness


Message Credibility

Peer Involvement


Connect to CoQ

Connect to GXPs


















Academic research








NIPTE (Currently)


httppharmahuborg









































LADMERMetabolites




























2014)

22(d)

192

100(a)

160(b)

110(a)

67(b)

68(a)

25(a)

67(a)

100(b)


22(d) 192 100(a) 160(b)110(a) 67(b) 68(a) 25(a)67(a) 100(b)






Yu Explains



on

rsquot f

org

et

fun

ctio

na

lity

o

f e

xcip

ien

ts i

s im

po

rta

nt





















to be truerdquo













































600 days










Initial

bull Unpredictable

Managed


Defined



bull In control

Optimizing




A validated process










Batch Rejection

Measured amp


Quality by Design

Quality Assured




attitude toward




test prone to error


a mistakerdquo

subjective norm


Compendial testing

sufficient

Indian regulators














Recent challenges


Th

e V

oic

e o

f th

eA

mer

ican

P

sych

iatr

ic A

sso

ciat

ion

and

th

e P

sych

iatr

ic C

om

mu

nit

y












bull Bioequivalence

bull Other studies

QbD Challenges




New and Generics





Summary








Ajaz S Hussain PhD








TransferCommercial




PQS Elements



Based on ICH Q10

























0

5

10

15

20

25

30

35

Yea

rs


0

50

100

150

200

250

300

350


1937

Eli

xir

of

Sulf

anil

amid

e

2007T

ootp

aste

conta

min

atio

n


Frequent reports

Mumbai Mumbai







doi101001jama279151175










children




glycol





be contaminated








the amount of DEG


(COA)







readily known

















substances



monographrsquos








testing












S

TF

Expanded frame

future

possibilities


and effectrsquo

Expanded frame

future

possibilities

people and

relationships

Narrow frame

the present

individuals and

relationships

Narrow frame

the present

objective

cause and

effect

N




Social

influences

Relative

thinking




do it


Consciously


Engineering Design

Plan-Do-Check-Act

Subconsciously



















the problem





doing



action










Error


Design flaws


Fear of error


Disregard to Malice














defenses

Preconditions







Subjective norm


control

IntentionFuture

Behavior



PastBehavior





QC Testing


Pharmacovigilence












play here









bullEQUIPMENTD















Subconsciously


CoQ How














Culture of Quality










quality

Leadership Emphasis

Message Credibility

Peer Involvement




Normal

(1)

Rewarding

(2)

Easy

(3)





guide










Theory of Knowledge

Knowledge about

Variation


A

B

C

D+








Error


Design flaws


Fear of error


D+



bull Anticipation





Mastery orientation




CoQ

1

2

3

QMS

A

B

C

D

GXP Behaviors

X

Y

Z


Culture of Quality

Normal

Rewarding

Easy

QMS

System

Knowledge

Variation

Behavior

Behavior -GXPs

Fear Removed

Mastery

Awareness


Message Credibility

Peer Involvement


Connect to CoQ

Connect to GXPs








































LADMERMetabolites




























2014)

22(d)

192

100(a)

160(b)

110(a)

67(b)

68(a)

25(a)

67(a)

100(b)


22(d) 192 100(a) 160(b)110(a) 67(b) 68(a) 25(a)67(a) 100(b)






Yu Explains



on

rsquot f

org

et

fun

ctio

na

lity

o

f e

xcip

ien

ts i

s im

po

rta

nt





















to be truerdquo













































600 days










Initial

bull Unpredictable

Managed


Defined



bull In control

Optimizing




A validated process










Batch Rejection

Measured amp


Quality by Design

Quality Assured




attitude toward




test prone to error


a mistakerdquo

subjective norm


Compendial testing

sufficient

Indian regulators














Recent challenges


Th

e V

oic

e o

f th

eA

mer

ican

P

sych

iatr

ic A

sso

ciat

ion

and

th

e P

sych

iatr

ic C

om

mu

nit

y












bull Bioequivalence

bull Other studies

QbD Challenges




New and Generics





Summary








Ajaz S Hussain PhD








TransferCommercial




PQS Elements



Based on ICH Q10

























0

5

10

15

20

25

30

35

Yea

rs


0

50

100

150

200

250

300

350


1937

Eli

xir

of

Sulf

anil

amid

e

2007T

ootp

aste

conta

min

atio

n


Frequent reports

Mumbai Mumbai







doi101001jama279151175










children




glycol





be contaminated








the amount of DEG


(COA)







readily known

















substances



monographrsquos








testing












S

TF

Expanded frame

future

possibilities


and effectrsquo

Expanded frame

future

possibilities

people and

relationships

Narrow frame

the present

individuals and

relationships

Narrow frame

the present

objective

cause and

effect

N




Social

influences

Relative

thinking




do it


Consciously


Engineering Design

Plan-Do-Check-Act

Subconsciously



















the problem





doing



action










Error


Design flaws


Fear of error


Disregard to Malice














defenses

Preconditions







Subjective norm


control

IntentionFuture

Behavior



PastBehavior





QC Testing


Pharmacovigilence












play here









bullEQUIPMENTD















Subconsciously


CoQ How














Culture of Quality










quality

Leadership Emphasis

Message Credibility

Peer Involvement




Normal

(1)

Rewarding

(2)

Easy

(3)





guide










Theory of Knowledge

Knowledge about

Variation


A

B

C

D+








Error


Design flaws


Fear of error


D+



bull Anticipation





Mastery orientation




CoQ

1

2

3

QMS

A

B

C

D

GXP Behaviors

X

Y

Z


Culture of Quality

Normal

Rewarding

Easy

QMS

System

Knowledge

Variation

Behavior

Behavior -GXPs

Fear Removed

Mastery

Awareness


Message Credibility

Peer Involvement


Connect to CoQ

Connect to GXPs






















2014)

22(d)

192

100(a)

160(b)

110(a)

67(b)

68(a)

25(a)

67(a)

100(b)


22(d) 192 100(a) 160(b)110(a) 67(b) 68(a) 25(a)67(a) 100(b)






Yu Explains



on

rsquot f

org

et

fun

ctio

na

lity

o

f e

xcip

ien

ts i

s im

po

rta

nt





















to be truerdquo













































600 days










Initial

bull Unpredictable

Managed


Defined



bull In control

Optimizing




A validated process










Batch Rejection

Measured amp


Quality by Design

Quality Assured




attitude toward




test prone to error


a mistakerdquo

subjective norm


Compendial testing

sufficient

Indian regulators














Recent challenges


Th

e V

oic

e o

f th

eA

mer

ican

P

sych

iatr

ic A

sso

ciat

ion

and

th

e P

sych

iatr

ic C

om

mu

nit

y












bull Bioequivalence

bull Other studies

QbD Challenges




New and Generics





Summary








Ajaz S Hussain PhD








TransferCommercial




PQS Elements



Based on ICH Q10

























0

5

10

15

20

25

30

35

Yea

rs


0

50

100

150

200

250

300

350


1937

Eli

xir

of

Sulf

anil

amid

e

2007T

ootp

aste

conta

min

atio

n


Frequent reports

Mumbai Mumbai







doi101001jama279151175










children




glycol





be contaminated








the amount of DEG


(COA)







readily known

















substances



monographrsquos








testing












S

TF

Expanded frame

future

possibilities


and effectrsquo

Expanded frame

future

possibilities

people and

relationships

Narrow frame

the present

individuals and

relationships

Narrow frame

the present

objective

cause and

effect

N




Social

influences

Relative

thinking




do it


Consciously


Engineering Design

Plan-Do-Check-Act

Subconsciously



















the problem





doing



action










Error


Design flaws


Fear of error


Disregard to Malice














defenses

Preconditions







Subjective norm


control

IntentionFuture

Behavior



PastBehavior





QC Testing


Pharmacovigilence












play here









bullEQUIPMENTD















Subconsciously


CoQ How














Culture of Quality










quality

Leadership Emphasis

Message Credibility

Peer Involvement




Normal

(1)

Rewarding

(2)

Easy

(3)





guide










Theory of Knowledge

Knowledge about

Variation


A

B

C

D+








Error


Design flaws


Fear of error


D+



bull Anticipation





Mastery orientation




CoQ

1

2

3

QMS

A

B

C

D

GXP Behaviors

X

Y

Z


Culture of Quality

Normal

Rewarding

Easy

QMS

System

Knowledge

Variation

Behavior

Behavior -GXPs

Fear Removed

Mastery

Awareness


Message Credibility

Peer Involvement


Connect to CoQ

Connect to GXPs






















to be truerdquo













































600 days










Initial

bull Unpredictable

Managed


Defined



bull In control

Optimizing




A validated process










Batch Rejection

Measured amp


Quality by Design

Quality Assured




attitude toward




test prone to error


a mistakerdquo

subjective norm


Compendial testing

sufficient

Indian regulators














Recent challenges


Th

e V

oic

e o

f th

eA

mer

ican

P

sych

iatr

ic A

sso

ciat

ion

and

th

e P

sych

iatr

ic C

om

mu

nit

y












bull Bioequivalence

bull Other studies

QbD Challenges




New and Generics





Summary








Ajaz S Hussain PhD








TransferCommercial




PQS Elements



Based on ICH Q10

























0

5

10

15

20

25

30

35

Yea

rs


0

50

100

150

200

250

300

350


1937

Eli

xir

of

Sulf

anil

amid

e

2007T

ootp

aste

conta

min

atio

n


Frequent reports

Mumbai Mumbai







doi101001jama279151175










children




glycol





be contaminated








the amount of DEG


(COA)







readily known

















substances



monographrsquos








testing












S

TF

Expanded frame

future

possibilities


and effectrsquo

Expanded frame

future

possibilities

people and

relationships

Narrow frame

the present

individuals and

relationships

Narrow frame

the present

objective

cause and

effect

N




Social

influences

Relative

thinking




do it


Consciously


Engineering Design

Plan-Do-Check-Act

Subconsciously



















the problem





doing



action










Error


Design flaws


Fear of error


Disregard to Malice














defenses

Preconditions







Subjective norm


control

IntentionFuture

Behavior



PastBehavior





QC Testing


Pharmacovigilence












play here









bullEQUIPMENTD















Subconsciously


CoQ How














Culture of Quality










quality

Leadership Emphasis

Message Credibility

Peer Involvement




Normal

(1)

Rewarding

(2)

Easy

(3)





guide










Theory of Knowledge

Knowledge about

Variation


A

B

C

D+








Error


Design flaws


Fear of error


D+



bull Anticipation





Mastery orientation




CoQ

1

2

3

QMS

A

B

C

D

GXP Behaviors

X

Y

Z


Culture of Quality

Normal

Rewarding

Easy

QMS

System

Knowledge

Variation

Behavior

Behavior -GXPs

Fear Removed

Mastery

Awareness


Message Credibility

Peer Involvement


Connect to CoQ

Connect to GXPs














































600 days










Initial

bull Unpredictable

Managed


Defined



bull In control

Optimizing




A validated process










Batch Rejection

Measured amp


Quality by Design

Quality Assured




attitude toward




test prone to error


a mistakerdquo

subjective norm


Compendial testing

sufficient

Indian regulators














Recent challenges


Th

e V

oic

e o

f th

eA

mer

ican

P

sych

iatr

ic A

sso

ciat

ion

and

th

e P

sych

iatr

ic C

om

mu

nit

y












bull Bioequivalence

bull Other studies

QbD Challenges




New and Generics





Summary








Ajaz S Hussain PhD








TransferCommercial




PQS Elements



Based on ICH Q10

























0

5

10

15

20

25

30

35

Yea

rs


0

50

100

150

200

250

300

350


1937

Eli

xir

of

Sulf

anil

amid

e

2007T

ootp

aste

conta

min

atio

n


Frequent reports

Mumbai Mumbai







doi101001jama279151175










children




glycol





be contaminated








the amount of DEG


(COA)







readily known

















substances



monographrsquos








testing












S

TF

Expanded frame

future

possibilities


and effectrsquo

Expanded frame

future

possibilities

people and

relationships

Narrow frame

the present

individuals and

relationships

Narrow frame

the present

objective

cause and

effect

N




Social

influences

Relative

thinking




do it


Consciously


Engineering Design

Plan-Do-Check-Act

Subconsciously



















the problem





doing



action










Error


Design flaws


Fear of error


Disregard to Malice














defenses

Preconditions







Subjective norm


control

IntentionFuture

Behavior



PastBehavior





QC Testing


Pharmacovigilence












play here









bullEQUIPMENTD















Subconsciously


CoQ How














Culture of Quality










quality

Leadership Emphasis

Message Credibility

Peer Involvement




Normal

(1)

Rewarding

(2)

Easy

(3)





guide










Theory of Knowledge

Knowledge about

Variation


A

B

C

D+








Error


Design flaws


Fear of error


D+



bull Anticipation





Mastery orientation




CoQ

1

2

3

QMS

A

B

C

D

GXP Behaviors

X

Y

Z


Culture of Quality

Normal

Rewarding

Easy

QMS

System

Knowledge

Variation

Behavior

Behavior -GXPs

Fear Removed

Mastery

Awareness


Message Credibility

Peer Involvement


Connect to CoQ

Connect to GXPs










Initial

bull Unpredictable

Managed


Defined



bull In control

Optimizing




A validated process










Batch Rejection

Measured amp


Quality by Design

Quality Assured




attitude toward




test prone to error


a mistakerdquo

subjective norm


Compendial testing

sufficient

Indian regulators














Recent challenges


Th

e V

oic

e o

f th

eA

mer

ican

P

sych

iatr

ic A

sso

ciat

ion

and

th

e P

sych

iatr

ic C

om

mu

nit

y












bull Bioequivalence

bull Other studies

QbD Challenges




New and Generics





Summary








Ajaz S Hussain PhD








TransferCommercial




PQS Elements



Based on ICH Q10

























0

5

10

15

20

25

30

35

Yea

rs


0

50

100

150

200

250

300

350


1937

Eli

xir

of

Sulf

anil

amid

e

2007T

ootp

aste

conta

min

atio

n


Frequent reports

Mumbai Mumbai







doi101001jama279151175










children




glycol





be contaminated








the amount of DEG


(COA)







readily known

















substances



monographrsquos








testing












S

TF

Expanded frame

future

possibilities


and effectrsquo

Expanded frame

future

possibilities

people and

relationships

Narrow frame

the present

individuals and

relationships

Narrow frame

the present

objective

cause and

effect

N




Social

influences

Relative

thinking




do it


Consciously


Engineering Design

Plan-Do-Check-Act

Subconsciously



















the problem





doing



action










Error


Design flaws


Fear of error


Disregard to Malice














defenses

Preconditions







Subjective norm


control

IntentionFuture

Behavior



PastBehavior





QC Testing


Pharmacovigilence












play here









bullEQUIPMENTD















Subconsciously


CoQ How














Culture of Quality










quality

Leadership Emphasis

Message Credibility

Peer Involvement




Normal

(1)

Rewarding

(2)

Easy

(3)





guide










Theory of Knowledge

Knowledge about

Variation


A

B

C

D+








Error


Design flaws


Fear of error


D+



bull Anticipation





Mastery orientation




CoQ

1

2

3

QMS

A

B

C

D

GXP Behaviors

X

Y

Z


Culture of Quality

Normal

Rewarding

Easy

QMS

System

Knowledge

Variation

Behavior

Behavior -GXPs

Fear Removed

Mastery

Awareness


Message Credibility

Peer Involvement


Connect to CoQ

Connect to GXPs











Batch Rejection

Measured amp


Quality by Design

Quality Assured




attitude toward




test prone to error


a mistakerdquo

subjective norm


Compendial testing

sufficient

Indian regulators














Recent challenges


Th

e V

oic

e o

f th

eA

mer

ican

P

sych

iatr

ic A

sso

ciat

ion

and

th

e P

sych

iatr

ic C

om

mu

nit

y












bull Bioequivalence

bull Other studies

QbD Challenges




New and Generics





Summary








Ajaz S Hussain PhD








TransferCommercial




PQS Elements



Based on ICH Q10

























0

5

10

15

20

25

30

35

Yea

rs


0

50

100

150

200

250

300

350


1937

Eli

xir

of

Sulf

anil

amid

e

2007T

ootp

aste

conta

min

atio

n


Frequent reports

Mumbai Mumbai







doi101001jama279151175










children




glycol





be contaminated








the amount of DEG


(COA)







readily known

















substances



monographrsquos








testing












S

TF

Expanded frame

future

possibilities


and effectrsquo

Expanded frame

future

possibilities

people and

relationships

Narrow frame

the present

individuals and

relationships

Narrow frame

the present

objective

cause and

effect

N




Social

influences

Relative

thinking




do it


Consciously


Engineering Design

Plan-Do-Check-Act

Subconsciously



















the problem





doing



action










Error


Design flaws


Fear of error


Disregard to Malice














defenses

Preconditions







Subjective norm


control

IntentionFuture

Behavior



PastBehavior





QC Testing


Pharmacovigilence












play here









bullEQUIPMENTD















Subconsciously


CoQ How














Culture of Quality










quality

Leadership Emphasis

Message Credibility

Peer Involvement




Normal

(1)

Rewarding

(2)

Easy

(3)





guide










Theory of Knowledge

Knowledge about

Variation


A

B

C

D+








Error


Design flaws


Fear of error


D+



bull Anticipation





Mastery orientation




CoQ

1

2

3

QMS

A

B

C

D

GXP Behaviors

X

Y

Z


Culture of Quality

Normal

Rewarding

Easy

QMS

System

Knowledge

Variation

Behavior

Behavior -GXPs

Fear Removed

Mastery

Awareness


Message Credibility

Peer Involvement


Connect to CoQ

Connect to GXPs



attitude toward




test prone to error


a mistakerdquo

subjective norm


Compendial testing

sufficient

Indian regulators














Recent challenges


Th

e V

oic

e o

f th

eA

mer

ican

P

sych

iatr

ic A

sso

ciat

ion

and

th

e P

sych

iatr

ic C

om

mu

nit

y












bull Bioequivalence

bull Other studies

QbD Challenges




New and Generics





Summary








Ajaz S Hussain PhD








TransferCommercial




PQS Elements



Based on ICH Q10

























0

5

10

15

20

25

30

35

Yea

rs


0

50

100

150

200

250

300

350


1937

Eli

xir

of

Sulf

anil

amid

e

2007T

ootp

aste

conta

min

atio

n


Frequent reports

Mumbai Mumbai







doi101001jama279151175










children




glycol





be contaminated








the amount of DEG


(COA)







readily known

















substances



monographrsquos








testing












S

TF

Expanded frame

future

possibilities


and effectrsquo

Expanded frame

future

possibilities

people and

relationships

Narrow frame

the present

individuals and

relationships

Narrow frame

the present

objective

cause and

effect

N




Social

influences

Relative

thinking




do it


Consciously


Engineering Design

Plan-Do-Check-Act

Subconsciously



















the problem





doing



action










Error


Design flaws


Fear of error


Disregard to Malice














defenses

Preconditions







Subjective norm


control

IntentionFuture

Behavior



PastBehavior





QC Testing


Pharmacovigilence












play here









bullEQUIPMENTD















Subconsciously


CoQ How














Culture of Quality










quality

Leadership Emphasis

Message Credibility

Peer Involvement




Normal

(1)

Rewarding

(2)

Easy

(3)





guide










Theory of Knowledge

Knowledge about

Variation


A

B

C

D+








Error


Design flaws


Fear of error


D+



bull Anticipation





Mastery orientation




CoQ

1

2

3

QMS

A

B

C

D

GXP Behaviors

X

Y

Z


Culture of Quality

Normal

Rewarding

Easy

QMS

System

Knowledge

Variation

Behavior

Behavior -GXPs

Fear Removed

Mastery

Awareness


Message Credibility

Peer Involvement


Connect to CoQ

Connect to GXPs











Recent challenges


Th

e V

oic

e o

f th

eA

mer

ican

P

sych

iatr

ic A

sso

ciat

ion

and

th

e P

sych

iatr

ic C

om

mu

nit

y












bull Bioequivalence

bull Other studies

QbD Challenges




New and Generics





Summary








Ajaz S Hussain PhD








TransferCommercial




PQS Elements



Based on ICH Q10

























0

5

10

15

20

25

30

35

Yea

rs


0

50

100

150

200

250

300

350


1937

Eli

xir

of

Sulf

anil

amid

e

2007T

ootp

aste

conta

min

atio

n


Frequent reports

Mumbai Mumbai







doi101001jama279151175










children




glycol





be contaminated








the amount of DEG


(COA)







readily known

















substances



monographrsquos








testing












S

TF

Expanded frame

future

possibilities


and effectrsquo

Expanded frame

future

possibilities

people and

relationships

Narrow frame

the present

individuals and

relationships

Narrow frame

the present

objective

cause and

effect

N




Social

influences

Relative

thinking




do it


Consciously


Engineering Design

Plan-Do-Check-Act

Subconsciously



















the problem





doing



action










Error


Design flaws


Fear of error


Disregard to Malice














defenses

Preconditions







Subjective norm


control

IntentionFuture

Behavior



PastBehavior





QC Testing


Pharmacovigilence












play here









bullEQUIPMENTD















Subconsciously


CoQ How














Culture of Quality










quality

Leadership Emphasis

Message Credibility

Peer Involvement




Normal

(1)

Rewarding

(2)

Easy

(3)





guide










Theory of Knowledge

Knowledge about

Variation


A

B

C

D+








Error


Design flaws


Fear of error


D+



bull Anticipation





Mastery orientation




CoQ

1

2

3

QMS

A

B

C

D

GXP Behaviors

X

Y

Z


Culture of Quality

Normal

Rewarding

Easy

QMS

System

Knowledge

Variation

Behavior

Behavior -GXPs

Fear Removed

Mastery

Awareness


Message Credibility

Peer Involvement


Connect to CoQ

Connect to GXPs








bull Bioequivalence

bull Other studies

QbD Challenges




New and Generics





Summary








Ajaz S Hussain PhD








TransferCommercial




PQS Elements



Based on ICH Q10

























0

5

10

15

20

25

30

35

Yea

rs


0

50

100

150

200

250

300

350


1937

Eli

xir

of

Sulf

anil

amid

e

2007T

ootp

aste

conta

min

atio

n


Frequent reports

Mumbai Mumbai







doi101001jama279151175










children




glycol





be contaminated








the amount of DEG


(COA)







readily known

















substances



monographrsquos








testing












S

TF

Expanded frame

future

possibilities


and effectrsquo

Expanded frame

future

possibilities

people and

relationships

Narrow frame

the present

individuals and

relationships

Narrow frame

the present

objective

cause and

effect

N




Social

influences

Relative

thinking




do it


Consciously


Engineering Design

Plan-Do-Check-Act

Subconsciously



















the problem





doing



action










Error


Design flaws


Fear of error


Disregard to Malice














defenses

Preconditions







Subjective norm


control

IntentionFuture

Behavior



PastBehavior





QC Testing


Pharmacovigilence












play here









bullEQUIPMENTD















Subconsciously


CoQ How














Culture of Quality










quality

Leadership Emphasis

Message Credibility

Peer Involvement




Normal

(1)

Rewarding

(2)

Easy

(3)





guide










Theory of Knowledge

Knowledge about

Variation


A

B

C

D+








Error


Design flaws


Fear of error


D+



bull Anticipation





Mastery orientation




CoQ

1

2

3

QMS

A

B

C

D

GXP Behaviors

X

Y

Z


Culture of Quality

Normal

Rewarding

Easy

QMS

System

Knowledge

Variation

Behavior

Behavior -GXPs

Fear Removed

Mastery

Awareness


Message Credibility

Peer Involvement


Connect to CoQ

Connect to GXPs


Summary








Ajaz S Hussain PhD








TransferCommercial




PQS Elements



Based on ICH Q10

























0

5

10

15

20

25

30

35

Yea

rs


0

50

100

150

200

250

300

350


1937

Eli

xir

of

Sulf

anil

amid

e

2007T

ootp

aste

conta

min

atio

n


Frequent reports

Mumbai Mumbai







doi101001jama279151175










children




glycol





be contaminated








the amount of DEG


(COA)







readily known

















substances



monographrsquos








testing












S

TF

Expanded frame

future

possibilities


and effectrsquo

Expanded frame

future

possibilities

people and

relationships

Narrow frame

the present

individuals and

relationships

Narrow frame

the present

objective

cause and

effect

N




Social

influences

Relative

thinking




do it


Consciously


Engineering Design

Plan-Do-Check-Act

Subconsciously



















the problem





doing



action










Error


Design flaws


Fear of error


Disregard to Malice














defenses

Preconditions







Subjective norm


control

IntentionFuture

Behavior



PastBehavior





QC Testing


Pharmacovigilence












play here









bullEQUIPMENTD















Subconsciously


CoQ How














Culture of Quality










quality

Leadership Emphasis

Message Credibility

Peer Involvement




Normal

(1)

Rewarding

(2)

Easy

(3)





guide










Theory of Knowledge

Knowledge about

Variation


A

B

C

D+








Error


Design flaws


Fear of error


D+



bull Anticipation





Mastery orientation




CoQ

1

2

3

QMS

A

B

C

D

GXP Behaviors

X

Y

Z


Culture of Quality

Normal

Rewarding

Easy

QMS

System

Knowledge

Variation

Behavior

Behavior -GXPs

Fear Removed

Mastery

Awareness


Message Credibility

Peer Involvement


Connect to CoQ

Connect to GXPs



Ajaz S Hussain PhD








TransferCommercial




PQS Elements



Based on ICH Q10

























0

5

10

15

20

25

30

35

Yea

rs


0

50

100

150

200

250

300

350


1937

Eli

xir

of

Sulf

anil

amid

e

2007T

ootp

aste

conta

min

atio

n


Frequent reports

Mumbai Mumbai







doi101001jama279151175










children




glycol





be contaminated








the amount of DEG


(COA)







readily known

















substances



monographrsquos








testing












S

TF

Expanded frame

future

possibilities


and effectrsquo

Expanded frame

future

possibilities

people and

relationships

Narrow frame

the present

individuals and

relationships

Narrow frame

the present

objective

cause and

effect

N




Social

influences

Relative

thinking




do it


Consciously


Engineering Design

Plan-Do-Check-Act

Subconsciously



















the problem





doing



action










Error


Design flaws


Fear of error


Disregard to Malice














defenses

Preconditions







Subjective norm


control

IntentionFuture

Behavior



PastBehavior





QC Testing


Pharmacovigilence












play here









bullEQUIPMENTD















Subconsciously


CoQ How














Culture of Quality










quality

Leadership Emphasis

Message Credibility

Peer Involvement




Normal

(1)

Rewarding

(2)

Easy

(3)





guide










Theory of Knowledge

Knowledge about

Variation


A

B

C

D+








Error


Design flaws


Fear of error


D+



bull Anticipation





Mastery orientation




CoQ

1

2

3

QMS

A

B

C

D

GXP Behaviors

X

Y

Z


Culture of Quality

Normal

Rewarding

Easy

QMS

System

Knowledge

Variation

Behavior

Behavior -GXPs

Fear Removed

Mastery

Awareness


Message Credibility

Peer Involvement


Connect to CoQ

Connect to GXPs






TransferCommercial




PQS Elements



Based on ICH Q10

























0

5

10

15

20

25

30

35

Yea

rs


0

50

100

150

200

250

300

350


1937

Eli

xir

of

Sulf

anil

amid

e

2007T

ootp

aste

conta

min

atio

n


Frequent reports

Mumbai Mumbai







doi101001jama279151175










children




glycol





be contaminated








the amount of DEG


(COA)







readily known

















substances



monographrsquos








testing












S

TF

Expanded frame

future

possibilities


and effectrsquo

Expanded frame

future

possibilities

people and

relationships

Narrow frame

the present

individuals and

relationships

Narrow frame

the present

objective

cause and

effect

N




Social

influences

Relative

thinking




do it


Consciously


Engineering Design

Plan-Do-Check-Act

Subconsciously



















the problem





doing



action










Error


Design flaws


Fear of error


Disregard to Malice














defenses

Preconditions







Subjective norm


control

IntentionFuture

Behavior



PastBehavior





QC Testing


Pharmacovigilence












play here









bullEQUIPMENTD















Subconsciously


CoQ How














Culture of Quality










quality

Leadership Emphasis

Message Credibility

Peer Involvement




Normal

(1)

Rewarding

(2)

Easy

(3)





guide










Theory of Knowledge

Knowledge about

Variation


A

B

C

D+








Error


Design flaws


Fear of error


D+



bull Anticipation





Mastery orientation




CoQ

1

2

3

QMS

A

B

C

D

GXP Behaviors

X

Y

Z


Culture of Quality

Normal

Rewarding

Easy

QMS

System

Knowledge

Variation

Behavior

Behavior -GXPs

Fear Removed

Mastery

Awareness


Message Credibility

Peer Involvement


Connect to CoQ

Connect to GXPs


























0

5

10

15

20

25

30

35

Yea

rs


0

50

100

150

200

250

300

350


1937

Eli

xir

of

Sulf

anil

amid

e

2007T

ootp

aste

conta

min

atio

n


Frequent reports

Mumbai Mumbai







doi101001jama279151175










children




glycol





be contaminated








the amount of DEG


(COA)







readily known

















substances



monographrsquos








testing












S

TF

Expanded frame

future

possibilities


and effectrsquo

Expanded frame

future

possibilities

people and

relationships

Narrow frame

the present

individuals and

relationships

Narrow frame

the present

objective

cause and

effect

N




Social

influences

Relative

thinking




do it


Consciously


Engineering Design

Plan-Do-Check-Act

Subconsciously



















the problem





doing



action










Error


Design flaws


Fear of error


Disregard to Malice














defenses

Preconditions







Subjective norm


control

IntentionFuture

Behavior



PastBehavior





QC Testing


Pharmacovigilence












play here









bullEQUIPMENTD















Subconsciously


CoQ How














Culture of Quality










quality

Leadership Emphasis

Message Credibility

Peer Involvement




Normal

(1)

Rewarding

(2)

Easy

(3)





guide










Theory of Knowledge

Knowledge about

Variation


A

B

C

D+








Error


Design flaws


Fear of error


D+



bull Anticipation





Mastery orientation




CoQ

1

2

3

QMS

A

B

C

D

GXP Behaviors

X

Y

Z


Culture of Quality

Normal

Rewarding

Easy

QMS

System

Knowledge

Variation

Behavior

Behavior -GXPs

Fear Removed

Mastery

Awareness


Message Credibility

Peer Involvement


Connect to CoQ

Connect to GXPs






doi101001jama279151175










children




glycol





be contaminated








the amount of DEG


(COA)







readily known

















substances



monographrsquos








testing












S

TF

Expanded frame

future

possibilities


and effectrsquo

Expanded frame

future

possibilities

people and

relationships

Narrow frame

the present

individuals and

relationships

Narrow frame

the present

objective

cause and

effect

N




Social

influences

Relative

thinking




do it


Consciously


Engineering Design

Plan-Do-Check-Act

Subconsciously



















the problem





doing



action










Error


Design flaws


Fear of error


Disregard to Malice














defenses

Preconditions







Subjective norm


control

IntentionFuture

Behavior



PastBehavior





QC Testing


Pharmacovigilence












play here









bullEQUIPMENTD















Subconsciously


CoQ How














Culture of Quality










quality

Leadership Emphasis

Message Credibility

Peer Involvement




Normal

(1)

Rewarding

(2)

Easy

(3)





guide










Theory of Knowledge

Knowledge about

Variation


A

B

C

D+








Error


Design flaws


Fear of error


D+



bull Anticipation





Mastery orientation




CoQ

1

2

3

QMS

A

B

C

D

GXP Behaviors

X

Y

Z


Culture of Quality

Normal

Rewarding

Easy

QMS

System

Knowledge

Variation

Behavior

Behavior -GXPs

Fear Removed

Mastery

Awareness


Message Credibility

Peer Involvement


Connect to CoQ

Connect to GXPs









the amount of DEG


(COA)







readily known

















substances



monographrsquos








testing












S

TF

Expanded frame

future

possibilities


and effectrsquo

Expanded frame

future

possibilities

people and

relationships

Narrow frame

the present

individuals and

relationships

Narrow frame

the present

objective

cause and

effect

N




Social

influences

Relative

thinking




do it


Consciously


Engineering Design

Plan-Do-Check-Act

Subconsciously



















the problem





doing



action










Error


Design flaws


Fear of error


Disregard to Malice














defenses

Preconditions







Subjective norm


control

IntentionFuture

Behavior



PastBehavior





QC Testing


Pharmacovigilence












play here









bullEQUIPMENTD















Subconsciously


CoQ How














Culture of Quality










quality

Leadership Emphasis

Message Credibility

Peer Involvement




Normal

(1)

Rewarding

(2)

Easy

(3)





guide










Theory of Knowledge

Knowledge about

Variation


A

B

C

D+








Error


Design flaws


Fear of error


D+



bull Anticipation





Mastery orientation




CoQ

1

2

3

QMS

A

B

C

D

GXP Behaviors

X

Y

Z


Culture of Quality

Normal

Rewarding

Easy

QMS

System

Knowledge

Variation

Behavior

Behavior -GXPs

Fear Removed

Mastery

Awareness


Message Credibility

Peer Involvement


Connect to CoQ

Connect to GXPs





S

TF

Expanded frame

future

possibilities


and effectrsquo

Expanded frame

future

possibilities

people and

relationships

Narrow frame

the present

individuals and

relationships

Narrow frame

the present

objective

cause and

effect

N




Social

influences

Relative

thinking




do it


Consciously


Engineering Design

Plan-Do-Check-Act

Subconsciously



















the problem





doing



action










Error


Design flaws


Fear of error


Disregard to Malice














defenses

Preconditions







Subjective norm


control

IntentionFuture

Behavior



PastBehavior





QC Testing


Pharmacovigilence












play here









bullEQUIPMENTD















Subconsciously


CoQ How














Culture of Quality










quality

Leadership Emphasis

Message Credibility

Peer Involvement




Normal

(1)

Rewarding

(2)

Easy

(3)





guide










Theory of Knowledge

Knowledge about

Variation


A

B

C

D+








Error


Design flaws


Fear of error


D+



bull Anticipation





Mastery orientation




CoQ

1

2

3

QMS

A

B

C

D

GXP Behaviors

X

Y

Z


Culture of Quality

Normal

Rewarding

Easy

QMS

System

Knowledge

Variation

Behavior

Behavior -GXPs

Fear Removed

Mastery

Awareness


Message Credibility

Peer Involvement


Connect to CoQ

Connect to GXPs




do it


Consciously


Engineering Design

Plan-Do-Check-Act

Subconsciously



















the problem





doing



action










Error


Design flaws


Fear of error


Disregard to Malice














defenses

Preconditions







Subjective norm


control

IntentionFuture

Behavior



PastBehavior





QC Testing


Pharmacovigilence












play here









bullEQUIPMENTD















Subconsciously


CoQ How














Culture of Quality










quality

Leadership Emphasis

Message Credibility

Peer Involvement




Normal

(1)

Rewarding

(2)

Easy

(3)





guide










Theory of Knowledge

Knowledge about

Variation


A

B

C

D+








Error


Design flaws


Fear of error


D+



bull Anticipation





Mastery orientation




CoQ

1

2

3

QMS

A

B

C

D

GXP Behaviors

X

Y

Z


Culture of Quality

Normal

Rewarding

Easy

QMS

System

Knowledge

Variation

Behavior

Behavior -GXPs

Fear Removed

Mastery

Awareness


Message Credibility

Peer Involvement


Connect to CoQ

Connect to GXPs















the problem





doing



action










Error


Design flaws


Fear of error


Disregard to Malice














defenses

Preconditions







Subjective norm


control

IntentionFuture

Behavior



PastBehavior





QC Testing


Pharmacovigilence












play here









bullEQUIPMENTD















Subconsciously


CoQ How














Culture of Quality










quality

Leadership Emphasis

Message Credibility

Peer Involvement




Normal

(1)

Rewarding

(2)

Easy

(3)





guide










Theory of Knowledge

Knowledge about

Variation


A

B

C

D+








Error


Design flaws


Fear of error


D+



bull Anticipation





Mastery orientation




CoQ

1

2

3

QMS

A

B

C

D

GXP Behaviors

X

Y

Z


Culture of Quality

Normal

Rewarding

Easy

QMS

System

Knowledge

Variation

Behavior

Behavior -GXPs

Fear Removed

Mastery

Awareness


Message Credibility

Peer Involvement


Connect to CoQ

Connect to GXPs








Error


Design flaws


Fear of error


Disregard to Malice














defenses

Preconditions







Subjective norm


control

IntentionFuture

Behavior



PastBehavior





QC Testing


Pharmacovigilence












play here









bullEQUIPMENTD















Subconsciously


CoQ How














Culture of Quality










quality

Leadership Emphasis

Message Credibility

Peer Involvement




Normal

(1)

Rewarding

(2)

Easy

(3)





guide










Theory of Knowledge

Knowledge about

Variation


A

B

C

D+








Error


Design flaws


Fear of error


D+



bull Anticipation





Mastery orientation




CoQ

1

2

3

QMS

A

B

C

D

GXP Behaviors

X

Y

Z


Culture of Quality

Normal

Rewarding

Easy

QMS

System

Knowledge

Variation

Behavior

Behavior -GXPs

Fear Removed

Mastery

Awareness


Message Credibility

Peer Involvement


Connect to CoQ

Connect to GXPs


Disregard to Malice














defenses

Preconditions







Subjective norm


control

IntentionFuture

Behavior



PastBehavior





QC Testing


Pharmacovigilence












play here









bullEQUIPMENTD















Subconsciously


CoQ How














Culture of Quality










quality

Leadership Emphasis

Message Credibility

Peer Involvement




Normal

(1)

Rewarding

(2)

Easy

(3)





guide










Theory of Knowledge

Knowledge about

Variation


A

B

C

D+








Error


Design flaws


Fear of error


D+



bull Anticipation





Mastery orientation




CoQ

1

2

3

QMS

A

B

C

D

GXP Behaviors

X

Y

Z


Culture of Quality

Normal

Rewarding

Easy

QMS

System

Knowledge

Variation

Behavior

Behavior -GXPs

Fear Removed

Mastery

Awareness


Message Credibility

Peer Involvement


Connect to CoQ

Connect to GXPs


Preconditions







Subjective norm


control

IntentionFuture

Behavior



PastBehavior





QC Testing


Pharmacovigilence












play here









bullEQUIPMENTD















Subconsciously


CoQ How














Culture of Quality










quality

Leadership Emphasis

Message Credibility

Peer Involvement




Normal

(1)

Rewarding

(2)

Easy

(3)





guide










Theory of Knowledge

Knowledge about

Variation


A

B

C

D+








Error


Design flaws


Fear of error


D+



bull Anticipation





Mastery orientation




CoQ

1

2

3

QMS

A

B

C

D

GXP Behaviors

X

Y

Z


Culture of Quality

Normal

Rewarding

Easy

QMS

System

Knowledge

Variation

Behavior

Behavior -GXPs

Fear Removed

Mastery

Awareness


Message Credibility

Peer Involvement


Connect to CoQ

Connect to GXPs




Subjective norm


control

IntentionFuture

Behavior



PastBehavior





QC Testing


Pharmacovigilence












play here









bullEQUIPMENTD















Subconsciously


CoQ How














Culture of Quality










quality

Leadership Emphasis

Message Credibility

Peer Involvement




Normal

(1)

Rewarding

(2)

Easy

(3)





guide










Theory of Knowledge

Knowledge about

Variation


A

B

C

D+








Error


Design flaws


Fear of error


D+



bull Anticipation





Mastery orientation




CoQ

1

2

3

QMS

A

B

C

D

GXP Behaviors

X

Y

Z


Culture of Quality

Normal

Rewarding

Easy

QMS

System

Knowledge

Variation

Behavior

Behavior -GXPs

Fear Removed

Mastery

Awareness


Message Credibility

Peer Involvement


Connect to CoQ

Connect to GXPs





QC Testing


Pharmacovigilence












play here









bullEQUIPMENTD















Subconsciously


CoQ How














Culture of Quality










quality

Leadership Emphasis

Message Credibility

Peer Involvement




Normal

(1)

Rewarding

(2)

Easy

(3)





guide










Theory of Knowledge

Knowledge about

Variation


A

B

C

D+








Error


Design flaws


Fear of error


D+



bull Anticipation





Mastery orientation




CoQ

1

2

3

QMS

A

B

C

D

GXP Behaviors

X

Y

Z


Culture of Quality

Normal

Rewarding

Easy

QMS

System

Knowledge

Variation

Behavior

Behavior -GXPs

Fear Removed

Mastery

Awareness


Message Credibility

Peer Involvement


Connect to CoQ

Connect to GXPs









play here









bullEQUIPMENTD















Subconsciously


CoQ How














Culture of Quality










quality

Leadership Emphasis

Message Credibility

Peer Involvement




Normal

(1)

Rewarding

(2)

Easy

(3)





guide










Theory of Knowledge

Knowledge about

Variation


A

B

C

D+








Error


Design flaws


Fear of error


D+



bull Anticipation





Mastery orientation




CoQ

1

2

3

QMS

A

B

C

D

GXP Behaviors

X

Y

Z


Culture of Quality

Normal

Rewarding

Easy

QMS

System

Knowledge

Variation

Behavior

Behavior -GXPs

Fear Removed

Mastery

Awareness


Message Credibility

Peer Involvement


Connect to CoQ

Connect to GXPs






bullEQUIPMENTD















Subconsciously


CoQ How














Culture of Quality










quality

Leadership Emphasis

Message Credibility

Peer Involvement




Normal

(1)

Rewarding

(2)

Easy

(3)





guide










Theory of Knowledge

Knowledge about

Variation


A

B

C

D+








Error


Design flaws


Fear of error


D+



bull Anticipation





Mastery orientation




CoQ

1

2

3

QMS

A

B

C

D

GXP Behaviors

X

Y

Z


Culture of Quality

Normal

Rewarding

Easy

QMS

System

Knowledge

Variation

Behavior

Behavior -GXPs

Fear Removed

Mastery

Awareness


Message Credibility

Peer Involvement


Connect to CoQ

Connect to GXPs









Subconsciously


CoQ How














Culture of Quality










quality

Leadership Emphasis

Message Credibility

Peer Involvement




Normal

(1)

Rewarding

(2)

Easy

(3)





guide










Theory of Knowledge

Knowledge about

Variation


A

B

C

D+








Error


Design flaws


Fear of error


D+



bull Anticipation





Mastery orientation




CoQ

1

2

3

QMS

A

B

C

D

GXP Behaviors

X

Y

Z


Culture of Quality

Normal

Rewarding

Easy

QMS

System

Knowledge

Variation

Behavior

Behavior -GXPs

Fear Removed

Mastery

Awareness


Message Credibility

Peer Involvement


Connect to CoQ

Connect to GXPs


CoQ How














Culture of Quality










quality

Leadership Emphasis

Message Credibility

Peer Involvement




Normal

(1)

Rewarding

(2)

Easy

(3)





guide










Theory of Knowledge

Knowledge about

Variation


A

B

C

D+








Error


Design flaws


Fear of error


D+



bull Anticipation





Mastery orientation




CoQ

1

2

3

QMS

A

B

C

D

GXP Behaviors

X

Y

Z


Culture of Quality

Normal

Rewarding

Easy

QMS

System

Knowledge

Variation

Behavior

Behavior -GXPs

Fear Removed

Mastery

Awareness


Message Credibility

Peer Involvement


Connect to CoQ

Connect to GXPs









Culture of Quality










quality

Leadership Emphasis

Message Credibility

Peer Involvement




Normal

(1)

Rewarding

(2)

Easy

(3)





guide










Theory of Knowledge

Knowledge about

Variation


A

B

C

D+








Error


Design flaws


Fear of error


D+



bull Anticipation





Mastery orientation




CoQ

1

2

3

QMS

A

B

C

D

GXP Behaviors

X

Y

Z


Culture of Quality

Normal

Rewarding

Easy

QMS

System

Knowledge

Variation

Behavior

Behavior -GXPs

Fear Removed

Mastery

Awareness


Message Credibility

Peer Involvement


Connect to CoQ

Connect to GXPs






quality

Leadership Emphasis

Message Credibility

Peer Involvement




Normal

(1)

Rewarding

(2)

Easy

(3)





guide










Theory of Knowledge

Knowledge about

Variation


A

B

C

D+








Error


Design flaws


Fear of error


D+



bull Anticipation





Mastery orientation




CoQ

1

2

3

QMS

A

B

C

D

GXP Behaviors

X

Y

Z


Culture of Quality

Normal

Rewarding

Easy

QMS

System

Knowledge

Variation

Behavior

Behavior -GXPs

Fear Removed

Mastery

Awareness


Message Credibility

Peer Involvement


Connect to CoQ

Connect to GXPs






guide










Theory of Knowledge

Knowledge about

Variation


A

B

C

D+








Error


Design flaws


Fear of error


D+



bull Anticipation





Mastery orientation




CoQ

1

2

3

QMS

A

B

C

D

GXP Behaviors

X

Y

Z


Culture of Quality

Normal

Rewarding

Easy

QMS

System

Knowledge

Variation

Behavior

Behavior -GXPs

Fear Removed

Mastery

Awareness


Message Credibility

Peer Involvement


Connect to CoQ

Connect to GXPs





Theory of Knowledge

Knowledge about

Variation


A

B

C

D+








Error


Design flaws


Fear of error


D+



bull Anticipation





Mastery orientation




CoQ

1

2

3

QMS

A

B

C

D

GXP Behaviors

X

Y

Z


Culture of Quality

Normal

Rewarding

Easy

QMS

System

Knowledge

Variation

Behavior

Behavior -GXPs

Fear Removed

Mastery

Awareness


Message Credibility

Peer Involvement


Connect to CoQ

Connect to GXPs









Error


Design flaws


Fear of error


D+



bull Anticipation





Mastery orientation




CoQ

1

2

3

QMS

A

B

C

D

GXP Behaviors

X

Y

Z


Culture of Quality

Normal

Rewarding

Easy

QMS

System

Knowledge

Variation

Behavior

Behavior -GXPs

Fear Removed

Mastery

Awareness


Message Credibility

Peer Involvement


Connect to CoQ

Connect to GXPs




bull Anticipation





Mastery orientation




CoQ

1

2

3

QMS

A

B

C

D

GXP Behaviors

X

Y

Z


Culture of Quality

Normal

Rewarding

Easy

QMS

System

Knowledge

Variation

Behavior

Behavior -GXPs

Fear Removed

Mastery

Awareness


Message Credibility

Peer Involvement


Connect to CoQ

Connect to GXPs




CoQ

1

2

3

QMS

A

B

C

D

GXP Behaviors

X

Y

Z


Culture of Quality

Normal

Rewarding

Easy

QMS

System

Knowledge

Variation

Behavior

Behavior -GXPs

Fear Removed

Mastery

Awareness


Message Credibility

Peer Involvement


Connect to CoQ

Connect to GXPs



Culture of Quality

Normal

Rewarding

Easy

QMS

System

Knowledge

Variation

Behavior

Behavior -GXPs

Fear Removed

Mastery

Awareness


Message Credibility

Peer Involvement


Connect to CoQ

Connect to GXPs


excipient knowledge management mumbai 12 march 2015 part 1 & 2

Health & Medicine

excipient knowledge

policy improvement3122015

critical3122015 ajaz

quality3122015 ajaz

shortages3122015 ajaz

human factors3122015

policy enforcement support

certain management practices