This document discusses management's responsibilities regarding quality systems. It notes that quality systems must be defined, documented, implemented and consistently followed to be effective and compliant. A key responsibility of management is to implement quality systems that include quality policies, objectives, plans, procedures, organizational structure, and resources. Management must also conduct reviews to ensure the quality system remains suitable and effective. Ignorance is not an excuse under strict liability regulations.

1. Quality Systems Thinking –
Management’s Responsibilities
Denise D. Dion,
Vice President Regulatory and Quality Services
EduQuest, Inc.
EduQ uest Education: Quality Engineering, Science, & Technology

2. EduQuest
EDUcation: 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 EduQ uest , I nc.
54

3. Denise Dion
Vice President,
Regulatory & Quality Services
EduQuest
• 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 EduQ uest , I nc.
55

4. Basic Quality System Concepts
“Quality has to be caused, not controlled.”
From “Philip Crosby's Reflections on Quality”
©2012 EduQ uest , I nc. 4

5. 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
©2012 EduQ uest , I nc. 5

6. “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
©2012 EduQ uest , I nc. 6

7. “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
©2012 EduQ uest , I nc. 7

8. 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
©2012 EduQ uest , I nc. 8

9. Underlying Principles
• 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
©2012 EduQ uest , I nc. 9

10. Underlying Principles
• 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
©2012 EduQ uest , I nc. 10

11. 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
©2012 EduQ uest , I nc. 9

12. US Regulatory Framework
• The US law –
– Federal Food, Drug, and Cosmetic Act
– Very different from other countries’
regulatory laws
– “Strict liability” criminal law
©2012 EduQ uest , I nc. 10

13. 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.
©2012 EduQ uest , I nc. 11

14. 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.”
©2012 EduQ uest , I nc. 12

15. Strict Liability – Supreme Court
Cases
• 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.”
©2012 EduQ uest , I nc. 13

16. Strict Liability – Supreme Court
Cases
• 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!
©2012 EduQ uest , I nc. 14

17. US Regulatory Framework
• FDA has enforcement responsibility and powers
– Not just a gatekeeper for the US market
– FDA acts as a law enforcement agency
©2012 EduQ uest , I nc. 15

18. 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
©2012 EduQ uest , I nc. 16

19. Federal Food, Drug, and Cosmetic Act
• 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!
©2012 EduQ uest , I nc. 17

20. Federal Food, Drug, and Cosmetic Act
• Regulation examples
– GMPs (Quality System Regulation for
Devices)
– GLPs
– BioResearch monitoring
©2012 EduQ uest , I nc. 18

21. FDA Regulations
• Regulations are . . .
– Quality standards
– Combination of subjective and objective
requirements
– Umbrella regulations
©2012 EduQ uest , I nc. 19

22. 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
©2012 EduQ uest , I nc. 22

23. 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
©2012 EduQ uest , I nc. 23

24. 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
©2012 EduQ uest , I nc. 24

25. 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 authorities
©2012 EduQ uest , I nc. 25

26. 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
©2012 EduQ uest , I nc. 26

27. 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?
©2012 EduQ uest , I nc. 27

28. 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
©2012 EduQ uest , I nc. 28

29. 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
©2012 EduQ uest , I nc. 29

30. Training
• Defined by Job Description
– Education
– Background
– Experience
• Defined in Training Matrix
– To procedures and processes and policies
– To the regulation, standards
©2012 EduQ uest , I nc. 30

31. Training
• Background, education and experience
– Resume, CV – Diplomas, course certificates
– Certifications or licenses
• Training
– Certificates
– In-house, 3rd party, etc.
• Training Folder
©2012 EduQ uest , I nc. 31

32. 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
©2012 EduQ uest , I nc. 32

33. 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
©2012 EduQ uest , I nc. 33

34. Common Traps and Failures
• 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
©2012 EduQ uest , I nc. 34

35. Common Traps and Failures
• 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
©2012 EduQ uest , I nc. 35

36. 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)
©2012 EduQ uest , I nc. 34

37. Inspection and Enforcement Process
• 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.
©2012 EduQ uest , I nc. 35

38. Inspection and Enforcement Process
• Understanding the FDA mindset
– Require objective evidence
– Not primarily focused on intent
– “If it isn’t documented, it didn’t happen”
©2012 EduQ uest , I nc. 36

39. 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)
©2012 EduQ uest , I nc. 37

40. Consequences of Non-Compliance
• Possible regulatory enforcement actions
– Disqualification of clinical investigators
– Initiation of the Application Integrity Policy
– Warning Letter (including sanctions)
– Product seizure
©2012 EduQ uest , I nc. 38

41. Consequences of Non-Compliance
• Possible regulatory enforcement actions
– Import restrictions
– Consent Decree
– Criminal prosecution
– Debarment
©2012 EduQ uest , I nc. 39

42. Consequences of Non-Compliance
• Other (non-regulatory) consequences
– Can be very significant
• Media coverage
• Competitors’ responses
• Litigation risks and costs
• Financial market reactions
©2012 EduQ uest , I nc. 40

43. What is a Consent Decree?
© 2012 EduQuest , I nc. 43

44. Recent Enforcement Developments
• Consent Decrees
– Schering Plough $500,000,000 +
– Abbott Laboratories $100,000,000 +
– Wyeth-Ayerst $30,000,000 +
©2012 EduQ uest , I nc. 42

45. Recent Enforcement Developments
• Criminal Plea Agreements
– Johnson & Johnson $60,000,000
– Roussel Uclaf $33,000,000
– Endovascular Technologies $92,400,000
©2012 EduQ uest , I nc. 43

46. 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
©2012 EduQ uest , I nc. 44

47. 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.”
©2012 EduQ uest , I nc. 45

48. 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
©2012 EduQ uest , I nc. 46

49. Developing Trends
• The expectations and approach are growing
beyond FDA and the US
– United Kingdom, European Community,
Australia, Germany, Japan, Brazil, China, India
©2012 EduQ uest , I nc. 47

50. 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
©2012 EduQ uest , I nc. 48

51. Recommendations for Success
• 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
©2012 EduQ uest , I nc. 49

52. Recommendations for Success
• 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
©2012 EduQ uest , I nc. 50

53. 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”
©2012 EduQ uest , I nc. 53

54. 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
©2012 EduQ uest , I nc. 52

55. Questions
or Comments?
Contact: denisedion@eduquest.net; 240-449-5852
EduQuest, Inc.
1896 Urbana Pike, Suite 14
Hyattstown, MD 20871
+1 (301) 874-6031
info@EduQuest.net
www.EduQuest.net
©2012 EduQ uest , I nc.
57

56. EduQuest
EDUcation: 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: Info@EduQuest.net
2012 EduQ uest , I nc. 56