Executive Management and Quality Systems Awareness Gordon B. Richman Vice President, EduQuest, Inc. EduQuest Education: Quality Engineering, Science &

Executive Management and Quality Systems Awareness

Gordon B. Richman

Vice President, EduQuest, Inc.

EduQuest Education: Quality Engineering, Science & Technology

© 2005 EduQuest, Inc.

Presentation Topics

• Quality Systems – How Your World is Changing

• Basic Quality System Purposes and Principles

• Management Responsibility in the U.S. Environment

• Business Impact – Costs, Benefits, and Challenges

• Critical Awareness and Recommendations for Success


The Changing World of GMP

• New quality systems based framework for GMP

– Not entirely new to FDA (experience with devices)

– Completely new to drug and biologics manufacturers

• FDA’s drug (CDER) and biologics (CBER) centers are

speaking a whole new language to these industries


FDA’s New GMP Initiative

• The next step in FDA’s and the industries’ evolution

Product Process Systems

- 1970s

Quality

ControlQuality

AssuranceQuality System

1980s - 1990s 21st Century *

* 1997 (Medical Devices)


FDA’s New GMP Initiative

• Major fundamental shift in FDA’s approach

– Focus on quality-by-design and the controlled

reduction of process and product variability

– An enormous change for the pharmaceutical

and biologics industries

– Eventually will deliver tremendous benefits


What Will Change?

• Process design, process controls, and resource allocations

– Based on “risk assessment” and “risk management”

• Long-standing concepts of “hazard control”

• FDA has mentioned FMEA and HACCP principles

• Not well-understood or routinely applied in the

drug and biologics industries


Important FDA Recognition

• “At the end of the CGMP Initiative the pharmaceutical

community has arrived at a cross-road; one path goes

toward the desired state and the other maintains the

current state. The path towards the desired state is

unfamiliar to many while the current state provides the

comfort of predictability. The Agency hopes the

pharmaceutical community will choose to move

towards the desired state.”


Key Components of FDA’s Model

• Management Responsibilities *

• Resources *

• Quality-by-Design and Product Development *

• Risk Management and Risk Assessment *

• CAPA (Corrective and Preventive Action) *

• Change Control

• The Quality Unit

• Six-System Inspection Model *


Note – What Isn’t New

• FDA is pushing for quality system approaches that

have been used for a long time in other industries

– For example, the electronics, defense, oil and

gas, and telecommunications industries

– How the drug and biologics industries compare

• Acceptable quality/defect levels and PAT


Impact on the Industry

• Will generate a lot of change and growing pains

• Huge increase in the need for early and very detailed

understanding of the process and product formulation

• GMP requirements will have much more impact on

pharmaceutical development – reaching back into

R&D more than our previous experience


Impact on the Industry

• This shift is going to take a substantial effort

– Ongoing dedication of more resources on the

“front end” of process design and development

– Years to realize the benefits on the “back end”

• Probably much more time, effort, people, and money

than the process validation movement in the 1980s


Basic Quality System Concepts

“Quality has to be caused, not controlled.”

From “Philip Crosby's Reflections on Quality”


Purposes of a Quality System

• To provide a defined operational framework

– Including appropriate and clearly documented

processes and procedures

• To assure that quality is designed and built in

• To provide documented, objective evidence of what

was done during design/development and manufacture


“Quality” and “Compliance”

• Quality and compliance are not the same

– Quality done right will result in compliance

– Compliance, on the other hand, will not necessarily

create or ensure the quality of processes or products

• Your organization must have both to succeed


“Quality” and “Compliance”

• The quality of a product is governed by the quality

of the processes used in its manufacture

– If you have poor processes and procedures,

complying with your quality system will just

ensure that you consistently have poor quality


Underlying Principles

• The quality system must be defined, documented,

implemented, and consistently followed to be

effective and compliant

• Constant self-critical and self-correcting loop

– Process and product knowledge, measurement,

control, and continuous improvement



• A compliant quality system starts and ends with

management (or it simply doesn’t exist)

– Management will be held legally responsible

for the effectiveness or non-effectiveness of

the quality system

– Every quality system failure can and will be

tied back to management



• Companies must implement “global” corrective and

preventive actions

– Similar changes should be made across all FDA-

regulated sites and operations

• Consistent with a systems-based approach

• Inconsistent with common industry practices


GMP and the U.S. Regulatory Scheme

• Management responsibility is a very serious matter

• The U.S. law – Federal Food, Drug, and Cosmetic Act

– “Strict liability” criminal law

• The law establishes “prohibited acts”

– Including key provisions that relate directly to GMP


Prohibited Acts and GMP

• Under the Food, Drug, and Cosmetic Act, it is illegal to -

– Manufacture, ship, deliver for shipment, or receive

after shipment an “adulterated or misbranded” food,

drug, device, or cosmetic


“Adulterated” Drugs and Devices

• A drug or device not produced in compliance with GMP

– So failure to comply with any of the GMP

requirements makes the product adulterated and

illegal by definition under U.S. law

– Even if there is no evidence of an integrity problem


FDA’s GMP Requirements

• The GMP regulations establish mandatory, minimum

requirements

– Compliance is not an option or a matter of choice

– Complying with GMP is the lowest acceptable

quality standard


Management Responsibility

• The cornerstone of quality systems and FDA’s approach

– Management cannot delegate its responsibility or just

designate someone else to be on the hook

– The old ways of corporate management (“that’s

Quality’s job”) are not going to work anymore


Management Responsibility

• Remember – this is a strict liability law

– Ignorance has never been a valid excuse

• Going forward, ignorance and/or a lack of direct

involvement will absolutely guarantee failure

– No matter how good your Quality organization is


FDA Recognizes Costs and Benefits

• “[I]mplementing an effective quality system in a

manufacturing organization will require significant

costs in time and resources. However, the long-

term benefits of implementing a quality system

will outweigh the costs.”


Significant Benefits in the Long Run

• Better science, efficiency, predictability, and control

– Real business benefits (in cost, time, and efforts)

– Less waste, rejection of materials, and re-work

– Improved process control and yields

– Problem avoidance through knowledge

– Greater ability to identify and correct root causes


Significant Benefits in the Long Run

• Improved ability to understand and implement

changes with less FDA oversight and pre-approval

• Faster and more predictable FDA review, analysis,

and approval of new products and CMC changes

• Fewer pre-approval and shorter GMP inspections


Big Challenges Ahead

• The basis for achieving all of the benefits will require

a substantial change in the industry’s business model

– Process understanding and development to a degree

that are far beyond the current way of working

– Shifting from a process focus to a systems focus

• Seeing all problems as quality system failures


Big Challenges Ahead

• Major challenge to overcome the current business

model and speed-to-market pressures

– Investing much more time and scientific effort

up front to be quicker on the “back end” of the

product life cycle – process transfer from R&D

to manufacturing, submission to FDA, and

throughout the commercial life of the product


Recommendations for Success

• The drug and biologics GMP regulations have not changed

– Quality system approach is only reflected in guidance

• FDA may revise the GMP regulations eventually

– Don’t wait for that to happen before moving forward

– The quality system train has already left the station


Philip Crosby's Reflections on Quality

“It is erroneous to think that quality is intangible,

and therefore unmeasurable. It is precisely

measurable by the oldest and most respected of

means – cold, hard cash.”

“The price of nonconformance in manufacturing

is more than your pretax profit.”


Critical Awareness and Acceptance

• New approach will require a significant culture change

– Going far beyond new policies, procedures, manuals,

standards, and training

– Truly affecting day-to-day operations and behavior

– A culture of resistance to change will not succeed



• Need to understand the seriousness and potential

consequences to the company and to individuals

– Throughout the entire company

– Every person in the organization needs to know

the rules of the game



• Changing the common mindset about quality issues

– Cannot just be resolved by the Quality organization

– Should be viewed as corporate governance problems

– Will need the full and active involvement of the

entire organization to be successful



• Management will need to demonstrate that the company

really “gets it” and is serious about its commitments

– Needs to be done through actions and not just words

– Cannot demonstrate it to FDA without clearly and

consistently demonstrating it internally


Common Traps and Failures

• The management “reality gap”– failure to recognize

significant gaps between senior management

perception of compliance issues and the reality of

the operations on the ground

– Often coincides with a corporate culture that does

not support or encourage the reporting of negative

information up through the chain of command



• The “no observation – no problem” rationale

– Management is not willing to correct a problem

until and unless FDA cites it in a 483 observation

– Sends a clear message that defects and poor quality

are acceptable as long as FDA doesn’t detect them



• A company’s view of “risk” should never include

what is commonly called “regulatory risk”

– The risk of detection of a problem by FDA

– The potential consequences of being “caught”

• FDA expects risk analyses to be documented, so

those documents are in-scope during inspections


Recommendations for Success

• Focus first on sound logic and good scientific practices

– This is what the regulators are usually looking for

• Companies fail because they continue to apply poor

practices that cannot be justified or defended

• “Do it right, and compliance will follow”


Questions?

Documents

Executive Management and Quality Systems Awareness Gordon B. Richman Vice President, EduQuest, Inc. EduQuest Education: Quality Engineering, Science &