management responsibility for fda quality systems

Quality Systems Thinking – Management’s Responsibilities

Denise D. Dion,

Vice President Regulatory and Quality Services

EduQuest, Inc.

EduQuest Education: Quality Engineering, Science, & Technology

EduQuestEDUcation: QUality Engineering, Science and Technology

• Global team of FDA compliance experts based near Washington, DC

• Founded by former senior officials & investigators from FDA’s Office of Regulatory Affairs (ORA) Headquarters

• Advising medical device and bio-pharmaceutical companies worldwide since 1995

• Focus on Audits and Training for Quality Systems, Risk Management, Part 11, Validation, Inspection Readiness

©2012 EduQuest, Inc.54

Denise DionVice President,

Regulatory & Quality ServicesEduQuest

• 18 years of experience with the U.S. FDA Office of Regulatory Affairs (ORA)

• Former FDA Medical Device Expert Investigator

• Developed many of FDA’s inspection guidance and training materials

• Primary editor of the FDA Investigations Operations Manual (IOM) – the “bible” for FDA inspectors

• Lead instructor for EduQuest CAPA, QSR Basics, and Design Control classroom training courses (www.EduQuest.net)


©2012 EduQuest, Inc.

Basic Quality System Concepts

“Quality has to be caused, not controlled.”

From “Philip Crosby's Reflections on Quality”

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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

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“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

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“Quality” and “Compliance”

• The quality of a product is governed by the quality

of the processes used in its design and manufacture

– If you have poor processes and procedures,

complying with your quality system will just

ensure that you consistently have poor quality

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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

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• 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

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• 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

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Why Focus on Responsibility?

• An inherent concept of all FDA regulation

• Establishes the context for understanding

• Provide a realistic view of

– The consequences of non-compliance

– Actions being taken by FDA


US Regulatory Framework

• The US law –

– Federal Food, Drug, and Cosmetic Act

– Very different from other countries’ regulatory laws

– “Strict liability” criminal law

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Strict Liability

• The FD&C Act is not like most other criminal laws

• The FD&C Act is a “strict liability” statute.– Management may be individually found

responsible for a violation of the FD&C Act – even though you did not participate in the violation, were not aware of the violation, and/or did not act with criminal intent – or even negligence.


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Strict Liability – Supreme Court Cases

• United States v. Dotterweich– “[This type of] legislation dispenses with the

conventional requirement for criminal conduct – awareness of some wrongdoing. In the interest of the larger good it puts the burden of acting at hazard upon a person otherwise innocent but standing in a responsible relationship to a public danger.”


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• United States v. Park– “Thus Dotterweich and the cases which have followed

[hold that] the [Food and Drugs] Act imposes not only a positive duty to seek out and remedy violations when they occur but also, and primarily, a duty to implement measures that will ensure that violations will not occur.”


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• United States v. Park– The court held that it’s not enough to correct– Management must make sure they prevent

reoccurrence or prevent occurrence in the first place!



US Regulatory Framework

• FDA has enforcement responsibility and powers

– Not just a gatekeeper for the US market

– FDA acts as a law enforcement agency


Federal Food, Drug, and Cosmetic Act

• Prohibited Acts

– The refusal to permit access to or the copying of records

– Causing the introduction into interstate commerce of an adulterated product



• Prohibited Acts

– The refusal to permit inspection

– The manufacture of any adulterated or misbranded food, drug, device, or cosmetic

Note: The FD&C Act states that products are adulterated if they are not made in compliance with cGMP

regulations!



• Regulation examples

– GMPs (Quality System Regulation for

Devices)

– GLPs

– BioResearch monitoring


FDA Regulations

• Regulations are . . .

– Quality standards

– Combination of subjective and objective requirements

– Umbrella regulations


FDA’s QSR Requirements

• The QSR regulations establish mandatory, minimum

requirements

– Compliance is not an option or a matter of choice

– Complying with QSR is the lowest acceptable

quality standard

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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

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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

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Management’s Responsibilities

• Management must implement a quality system

that includes – A quality policy

– Quality objectives

– Quality plan and quality system procedures

– Identification of a management representative

– Adequate organizational structure and resources

– Appropriate responsibilities and authorities25


Management Reviews

• Management reviews must be conducted to review the suitability and effectiveness of the quality system at defined intervals of sufficient frequency

– Written procedures and schedule

– Documented dates and results

• Focus on the health of the Quality System

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Management Reviews

• Not just how many CAPAs, or complaints or how many are late, or how many recalls or MDRs

• Why are we having problems?

– Root Cause

– What part of the Quality System isn’t working and why?

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Resources

• Money – to fund improvements, hire staff

• Time – to do it right

• People – knowledge, training, experience, sufficient number

• Facilities – space, cleanliness

• Equipment – the correct equipment, maintained, calibrated

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Quality Audits

• Quality audits to assure the quality system is in compliance with established QS requirements and to determine effectiveness

– Conducted by independent individual(s)

– Corrective actions of deficiencies

– Re-audits of deficient matters

– Reports made and reviewed by management responsible for the areas audited

– Dates and results documented

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Training

• Defined by Job Description

– Education

– Background

– Experience

• Defined in Training Matrix

– To procedures and processes and policies

– To the regulation, standards

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Training

• Background, education and experience

– Resume, CV – Diplomas, course certificates

– Certifications or licenses

• Training

– Certificates

– In-house, 3rd party, etc.

• Training Folder

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Critical Awareness and Acceptance

• 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

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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

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• 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

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• 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

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Inspection and Enforcement Process

• FDA inspections can occur for several reasons

– Routine GMP inspection (usually every 2-3 years)

– Routine Bioresearch Monitoring (GLP/GCP) inspection

– Pre-approval request (e.g., for a new product or process change)

– FDA concern (e.g., after a complaint or recall)



• FDA has regulatory authority over a broad range of products and industries including foods, drugs (human and animal), medical devices, biologic products, radiation emitting products, etc.

• Each set of regulations for these products and industries include provisions for responsibility and accountability.



• Understanding the FDA mindset

– Require objective evidence

– Not primarily focused on intent

– “If it isn’t documented, it didn’t happen”


Consequences of Non-Compliance

• Possible regulatory enforcement actions

– Disqualification of a nonclinical laboratory

– Clinical hold or termination

– Delay in approval of new products or facilities

– Rejection of application data (e.g., clinical trials)




– Disqualification of clinical investigators

– Initiation of the Application Integrity Policy

– Warning Letter (including sanctions)

– Product seizure




– Import restrictions

– Consent Decree

– Criminal prosecution

– Debarment



• Other (non-regulatory) consequences

– Can be very significant

• Media coverage

• Competitors’ responses

• Litigation risks and costs

• Financial market reactions


Recent Enforcement Developments

• Consent Decrees

– Schering Plough $500,000,000 +

– Abbott Laboratories $100,000,000 +

– Wyeth-Ayerst $30,000,000 +


Recent Enforcement Developments

• Criminal Plea Agreements

– Johnson & Johnson $60,000,000

– Roussel Uclaf $33,000,000

– Endovascular Technologies $92,400,000


Recent Consent Decrees

• Initial “fines” of 30 to 500 million dollars

• Ongoing forfeiting (“disgorgement”) of profits

• Additional penalties for missing deadlines

• Very heavy FDA involvement and review

• Corporate executives signed as individual defendants


FDA Press Release

• “Manufacturers who choose to wait until FDA

investigators find violations rather than policing

themselves will find that they have made a poor and

costly mistake.”


Developing Trends

• FDA expects companies to implement “global” corrective actions

– Similar corrective changes should be made across all FDA-regulated sites and operations

– Consistent with a quality system approach

– Inconsistent with common industry practices


Developing Trends

• The expectations and approach are growing

beyond FDA and the US

– United Kingdom, European Community,

Australia, Germany, Japan, Brazil, China, India


Recommendations for Success

• Understand the US regulatory framework

– Scope of FDA’s inspectional authority and enforcement powers

– Expectations regarding basic good practices, effective management, and control

– Changing regulatory environment



• Be realistic and accurate

– Common industry perception that FDA and its approach are “over the top”

– Most inspectional observations focus on very basic compliance issues and operational controls

– Understand your current practices and challenge your assumptions



• Much less costly to be proactive and protective

– Once detected, it may cost over 100 times more to resolve the problems to FDA’s satisfaction

– In this area, an ounce of prevention is worth much more than a pound of cure



• 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”

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Quality System

• The Quality System is the responsibility of everyone. It is not owned by quality assurance!

• Quality must be built into the process• Quality is not tested into the product• Assurance of Quality comes from

– Design of robust products and processes based on thorough knowledge of those products and processes and the sources of variability

– Effective Quality System in place

Questions or Comments?

Contact: [email protected]; 240-449-5852

EduQuest, Inc.1896 Urbana Pike, Suite 14

Hyattstown, MD 20871+1 (301) [email protected]


EduQuestEDUcation: QUality Engineering, Science and Technology

Additional Opportunity for Staff Training from EduQuest:

The CAPA Confidence Clinic: Effective CAPA Systems, Failure Investigations & Complaint Management

• September 27-28, 2012 – Frederick, MD (near Baltimore and Washington, DC)

QSR Compliance Basics: Complying with FDA’s Medical Device 21 CFR 820 Quality System Regulation

• October 16-17, 2012 – Frederick, MD (near Baltimore and Washington, DC)

Design Control for Medical Devices: Meeting FDA’s 21 CFR 820.30 Rules for Quality Design and Manufacturing

• October 17-19, 2012 – Frederick, MD (near Baltimore and Washington, DC)

Details at www.EduQuest.net Or Email: [email protected]

2012 EduQuest, Inc. 56

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