This presentation is about the design and implementation of Quality Management Systems (QMS) in different industries. In this presentation you will learn more about the history and development of quality management systems (QMS), the importance and benefits of a QMS for various industries, quality principles and Good Manufacturing Practices (GMP) in life sciences, the most important requirements of an ISO 9001 QMS, the most important requirements of GMP regulations and how to develop and implement a QMS for various industries. The speakers, Luc Marivoet and Luc Huybreghts, both work in very different industries. They both talked about quality management systems from their own experience and very different and interesting angles. This presentation is ideal for all professionals who want to include quality management in their projects and daily activities and who want to take the overall quality level of their organization to the next level. Do you have any questions regarding quality management or the implementation of a QMS for your organization? Don't hesitate and visit our website at www.pauwelsconsulting.com

1. Quality Management Systems (QMS)
Luc Marivoet & Luc Huybreghts Antwerp, March 30 , 2017

2. 22
0 Presented by
Luc Marivoet, Senior Consultant QM / Engineering Services
Luc Huybreghts, Senior Consultant QA & Compliance
Lecturers Using Craftsmanship in QMS

3. 33
0 Goal
The goal of today’s session:
Guide you through the world of Quality Management Systems (QMS)
• What is a QMS
• Importance & benefits of a QMS
• Different types of Quality Management Systems:
• Process-oriented : ISO 9001 – Luc Marivoet
• Product-oriented : cGxP – Luc Huybreghts
• ISO 9001 and cGxP: a comparison
• Conclusion

4. 44
1 A brief history of Quality
How it started
Handcrafting
Industrial Revolution
Mass production
Deming, Juran and Japan
Improving organizational process
World War II
Sampling for inspection
The American Response
Total Quality Management
Late 20th Century
Quality Management System

5. 55
What
• Definition: A system by which an organization aims to reduce and
eventually eliminate nonconformance to specifications, standards, and
customer expectations in the most cost effective and efficient manner.
Benefits
• Meeting customer’s requirements
• Meeting organization’s requirements
2 Quality Management Systems
Different approaches
• Process-oriented: ISO 9001
• Product-oriented: cGMP

6. 66
2 Quality Management Systems

7. 77
What
• Most popular standard.
• Agreement or best practice.
• Reflects professionalism.
Benefits
• Consistent quality.
• Meet the customer’s requirements.
• Comply with the law and legislation.
• Meet the organisation’s own requirements.
• Streamline your business processes.
• Increase customer satisfaction.
3 Quality Management System ISO 9001

8. 88
3 Quality Management System ISO 9001
Historical timeline
ISO
9001:1987
Procedures
ISO
9001:1994
Say what you do
& do what you say
ISO
9001:2000
Process Approach
& PDCA
ISO
9001:2008
Process Approach
& PDCA
ISO
9001:2015
Context
Risk / Opportunity

9. 99
Normative reference
• QMS standards for which ISO 9001 is a normative reference:
3 Quality Management System ISO 9001

10. 1010
ISO 9000 series
3 Quality Management System ISO 9001
ISO 9000
Quality
Management
Systems
–
Fundamentals and
vocabulary
ISO 9001
Quality
Management
Systems
–
Requirements
ISO/TS 9002
Quality
Management
Systems
–
Guidelines for the
application of
ISO 9001:2015

11. 1111
3 Quality Management System ISO 9001
Plug-in model

12. 1212
4 Quality Management Principles
1. Customer
Focus
2. Leadership
3.
Engagement
of people
4. Process
Approach
5.
Improvement
6. Evidence-
based
Decision
Making
7.
Relationship
Management

13. 1313
5 Key Requirements of ISO 9001

14. 1414
4. Context of the organization
• Understanding the organization and its context.
• Understanding the needs and expectations of interested parties.
• Determining the scope of the quality management system.
• Quality management system and its processes.
5 Key Requirements of ISO 9001

15. 1515
4. Context of the organization
• Understanding the organization and its context.
5 Key Requirements of ISO 9001
POLITICALTECHNOLOGYMARKET
RESOURCESHUMANASPECTSOPERATIONAL
S
T
R
A
T
E
G
Y
EXTERNAL ISSUES INTERNAL ISSUES

16. 1616
4. Context of the organization
• Understanding the organization and its context.
5 Key Requirements of ISO 9001
STRENGTH WEAKNESS
OPPORTUNITY THREAT
InternExtern

17. 1717
4. Context of the organization
• Understanding the needs and expectations of interested parties.
5 Key Requirements of ISO 9001

18. 1818
4. Context of the organization
• Determining the scope of the quality management system.
5 Key Requirements of ISO 9001

19. 1919
4. Context of the organization
• Quality management system and its processes.
5 Key Requirements of ISO 9001

20. 2020
4. Context of the organization
• Quality management system and its processes.
5 Key Requirements of ISO 9001

21. 2121
5. Leadership
• Leadership and commitment.
• Policy.
• Organizational roles, responsibilities and authorities.
5 Key Requirements of ISO 9001

22. 2222
5. Leadership
• Leadership and commitment.
• Policy.
• Organizational roles, responsibilities and authorities.
5 Key Requirements of ISO 9001

23. 2323
6. Planning
• Actions to address risks and opportunities.
• Quality objectives and planning to achieve them.
• Planning of changes.
5 Key Requirements of ISO 9001

24. 2424
6. Planning
• Actions to address risks and opportunities.
5 Key Requirements of ISO 9001

25. 2525
6. Planning
• Actions to address risks and opportunities.
5 Key Requirements of ISO 9001

26. 2626
6. Planning
• Quality objectives and planning to achieve them.
5 Key Requirements of ISO 9001

27. 2727
6. Planning
• Quality objectives and planning to achieve them.
5 Key Requirements of ISO 9001

28. 2828
6. Planning
• Planning of changes.
5 Key Requirements of ISO 9001

29. 2929
7. Support
• Resources.
• Competence.
• Awareness.
• Communication.
• Documented information.
5 Key Requirements of ISO 9001

30. 3030
7. Support
• Resources.
5 Key Requirements of ISO 9001

31. 3131
7. Support
• Competence.
5 Key Requirements of ISO 9001

32. 3232
7. Support
• Competence.
5 Key Requirements of ISO 9001

33. 3333
7. Support
• Awareness.
5 Key Requirements of ISO 9001

34. 3434
7. Support
• Communication.
5 Key Requirements of ISO 9001

35. 3535
7. Support
• Communication.
5 Key Requirements of ISO 9001

36. 3636
7. Support
• Documented information.
5 Key Requirements of ISO 9001

37. 3737
7. Support
• Documented information.
5 Key Requirements of ISO 9001

38. 3838
8. Operation
• Operational planning and control.
• Requirements for products and services.
• Design and development of products and services.
• Control of externally provided processes, products and services.
• Production and service provision / Release of products and services.
• Control of nonconforming outputs.
5 Key Requirements of ISO 9001

39. 3939
8. Operation
• Operational planning and control.
5 Key Requirements of ISO 9001

40. 4040
8. Operation
• Operational planning and control.
5 Key Requirements of ISO 9001

41. 4141
8. Operation
• Requirements for products and services.
5 Key Requirements of ISO 9001

42. 4242
8. Operation
• Requirements for products and services.
5 Key Requirements of ISO 9001

43. 4343
8. Operation
• Design and development of products and services.
5 Key Requirements of ISO 9001

44. 4444
8. Operation
• Design and development of products and services.
5 Key Requirements of ISO 9001

45. 4545
8. Operation
• Control of externally provided processes, products and services.
5 Key Requirements of ISO 9001

46. 4646
8. Operation
• Production and service provision.
• Release of products and services.
• Control of nonconforming outputs.
5 Key Requirements of ISO 9001

47. 4747
9. Performance evaluation
• Monitoring, measurement, analysis and evaluation.
• Internal audit.
• Management review.
5 Key Requirements of ISO 9001

48. 4848
9. Performance evaluation
• Monitoring, measurement, analysis and evaluation.
5 Key Requirements of ISO 9001

49. 4949
9. Performance evaluation
• Monitoring, measurement, analysis and evaluation.
5 Key Requirements of ISO 9001

50. 5050
9. Performance evaluation
• Internal audit.
5 Key Requirements of ISO 9001

51. 5151
9. Performance evaluation
• Internal audit.
5 Key Requirements of ISO 9001

52. 5252
9. Performance evaluation
• Management review.
5 Key Requirements of ISO 9001

53. 5353
10. Improvement
• Nonconformity and corrective action.
• Continual improvement.
5 Key Requirements of ISO 9001

54. 5454
10. Improvement
• Nonconformity and corrective action.
5 Key Requirements of ISO 9001
NONCONFORMITY CORRECTION
CORRECTIVE ACTION ACTION TO ADDRESS THE RISK

55. 5555
10. Improvement
• Continual improvement.
5 Key Requirements of ISO 9001

56. 5656
QUESTIONS
6 Questions

57. 5757
What
• Definition: A system by which an organization aims to reduce and
eventually eliminate nonconformance to specifications, standards, and
customer expectations in the most cost effective and efficient manner.
Benefits
• Meeting customer’s requirements
• Meeting organization’s requirements
RQuality Management Systems
Different approaches
• Process-oriented: ISO 9001
• Product-oriented: cGMP

58. 5858
RQuality Management Systems

59. 5959
Good Manufaturing Practices
• What – why
• Historical overview
• Structure
• Eudralex
• FDA
• Evolution – latest trends
• Dangers & pittfalls
• Business enabler
Comparison & relation with ISO
Conclusion
cGMP

60. 6060
cGMP
Do you trust the pill you took today ?
The Matrix

61. 6161
cGMP
Quality should be built into the product
and testing alone cannot be relied on
to ensure product quality.

62. 6262
cGMP
The function holder will maintain a Pharmaceutical Quality System as defined in
Article 47 of Directive 2001/83/EC and laid down in Eudralex Volume 4 GMP guidelines;
in both GMP and GDP requirements and in ISO standards
Responsibilities:
• Review and improve the Quality Management System
• Coordinate the quality system activities
• Ensure that necessary KPI’s are in place
• Coordinate the activities of inspection readiness and ISO certification
• Definition of Quality Objectives and development of a Quality Mindset
• Provide input for Quality Improvement Meetings and Quality Review Meetings

63. 6363
What
• current Good Manufacturing Practices
• Pharmaceutical industry – life-sciences
• It is the LAW – regulatory authorities
Belgium: FAGG
Brazil: ANVISA
EU: EMA
UK: MHRA
USA: FDA
cGMP

64. 6464
India
Israel
Biologics
Control Act
Federal Food,
Drug and
Cosmetic Act
Guidance
Documents
Chinese
Milk Scandal
Tylenol
Thalidomide
The Pure Food and Drug Act
Public Health
Services Act
Update
Eudralex
Chapter 1
cGMP - timeline

65. 6565
What
• minimum requirements – what to do, never how
• Current: continuous improvement – use up-to-date techniques
• Flexible
• cGxP
cGxP
Finding
Proof of
Principle
Animal
Studies
Clin.
Phase
I
Clin.
Phase
II
Clin.
Phase
III
Market
GLP GMP
GCP
GMP
GDP

66. 6666
Why
• patient protection
• a response of the authorities
• prevent future tragedies
• processes: reliable and reproducible
• quality is built into the design and manufacturing – at each step
• identity, strenght, quality and purity of drug products
cGMP

67. 6767
cGxP – general
Combination of regulations and guidelines
Regulatory Authorities:
Argentina Egypt Romania
Australia FDA Saudi Arabia
Austria ICH Singapore
ANVISA India S. Africa
Canada Ireland S. Korea
China Italy UAE
Czech Rep. Malaysia Venezuela
EU Mexico
MHRA
Guidance standards
ICH International Conference of Harmonisation
PDA Parenteral Drug Association
PIC/S Pharmaceutical Inspection
Convention
Mandatory standards
WHO – World Health Organization

68. 6868
Latest trends in cGMP:
• ICH – International Conference on Harmonization of technical
requirements for registration of pharmaceuticals for human
use
• EU – Japan – USA: harmonization
• April 1990: Brussels
• Q9 – Risk Assessment
• Q10 – Pharmaceutical Quality Systems
• Q11 – Development and manufacturing of drug substances (draft)
cGMP

69. 6969
Latest trends in cGMP:
• PDA – technical reports – industry practices
• PIC/S : partner of WHO, Unicef, EMA – 46 countries
• Facilitate to maintain mutual confidence
• Exchange cGMP information and experience
• www.picscheme.org
cGMP

70. 7070
Structure GMP (Eudralex volume 4)
• Part 1: GMP Chapters + Annexes (19 Guidelines)
cGMP
GMP Chapters (Part1) Annexes
1. Pharmaceutical Quality System 1. Manufacture of Sterile Products
2. Personnel 2. Manufacture of Biological active
substances and Products for human use
3. Premise and Equipment 3. Manufacture of Veterinary Products
4. Documentation 6. Manufacture of Medicinal Gases
5. Production 9. Manufacture of Liquids, Creams and
Ointments
6. Quality Control 11. Computerised Systems
7. Outsourced Activities 15. Qualification and Validation
8. Complaints and recall 17. Parametric Release
9. Self Inspection 19. Reference and Retention Samples

71. 7171
Structure GMP (Eudralex volume 4)
• Part 1: GMP Chapters + Annexes: 1-19 (guidelines)
• Part 2: Basic Requirements for Active Substances used as starting
materials
• Part 3 – GMP related documents
o Site Master File
o Q9 Quality Risk Management
o Q10 Guidance on Pharmaceutical Quality System
o MRA Batch Certificate
cGMP

72. 7272
Structure GMP (FDA Code of Federal Regulations)
US FDA Title 21 CFR Parts
• Part 11 – electronic records and signatures
• Part 210 – Current Good Manufacturing Practices in Manufacturing,
Processing, Packaging or Holing of Drugs; General
• Part 211 – Current Good Manufacturing Practice for Finished
Pharmaceuticals
• Part 600 – Biological Products: general
• Part 601 – Licensing Biologics
• Part 610 – General Biological Products Standards
cGMP

73. 7373
Structure GMP (FDA Code of Federal Regulations)
Guidance Documents – Guidance for industry
Implement modern quality systems – risk management
cGMP

74. 7474
Inspection by regulatory bodies:
• Regular inspections
• Pre-approval inspections (PAI)
• System based inspections:
full ≥ 4 systems
partial ≥ 2 systems
• Observations:
• 483 – warning letter
• published
cGMP

75. 7575
GxP-basic QMS model
Resource
• Raw materials
• Packaging materials
• Personnel: training
& hygiene
• Premises & equipment
• Maintenance
• Calibration
• Environmental monitoring
• Validation
• Processing
• Quality Control
• Warehousing
• Distribution
Manufacture
• Quality
Management
• Key Personnel
• Documentation
• Complaints
& recall
• Self inspection
System Control
Quality Data
• Batch records
• Samples
• Release
• Products
• Patients

76. 7676
Management responsibilities
PQS elements: process performance – product quality monitoring
system – CAPA system – Change Control system
management review system
Enablers:knowledge management – quality risk management
Pharmaceutical
development
Technology
Transfer
Commercial
manufacturing
Product
discontinuation
cGxP
Investigational
products
cGMP - PQS
Pharmaceutical Quality System

77. 7777
1. Management belief – commitment
Sometimes we can’t follow procedures. We have a business to run.
The validation results were marginal. We can improve the process later.
We often see this manufacturing problem. We routinely rework and 100% inspect.
That test result is barely out of spec. We know it is good product to release.
• cGMP compliance is not a frustrating hurdle to get product to the market
• Company culture
• Daily experience with pharmaceutical quality assurance is lacking
• Walk the talk
cGMP - Pittfalls

78. 7878
2. Quality function is detached from operations
I know this is a compliant procedure. I used it at my last company
You are not following cGMP’s. You are supposed to use blue ink.
I’m not going to deliver the bad news. That would kill my career.
Don’t talk to me about cost. Quality doesn’t care about cost.
• Quality unit – regulated by Code of Federal Regulations
• Develop procedures in isolation – no integration
• A partner – do not lose independence
• QA professionals must have a working and process knowledge
• QA professionals must have core skills, not just cGMP compliance
cGMP - Pittfalls

79. 7979
3. Inadequate management review
Are we ready for an inspection? Quality had better be sure we are.
Backlog of overdue investigations again ? Dedicate a team to close them ASAP
A repeated inspection observation? I thought we resolved that problem
• Management personally responsible
• State of cGMP compliance of their operation – QMS metrics
• Quality Management Review
• Logical PQS – not a random collection of poorly written procedures
• 4 basic management questions
• System owners are responsible for the metrics and present them
cGMP - Pittfalls

80. 8080
4. Large scale cGMP performance improvement
The CAPA implementation efforts are going nowhere. Manufacturing
department says their priority is the production schedule
We agreed that on-the-job-training is needed to reduce the human error rate,
but we were just told to cut our training budget by 20%.
We know that unavailability of clean vessels cause a bottleneck in the
manufacturing schedule, but our capital request are continuously denied.
• Warning letters are phrased as failures of the quality unit
• Problems are often site-wide – multiple functions have to collaborate
• Align support for cGMP initiatives
cGMP - Pittfalls

81. 8181
cGMP an obstacle for business ?
• Business enabler:
• Individual dose – every day – not an average quality
• Quality only happens intentionally
• Quality can’t be tested into a product
• Standard operating procedures
• Documentation proves the work
• Records – performance metrics
• Review and trending
anticipating organization, not a reactive one
cGMP

82. 8282
Similarities
• Written procedures and records
• Controlled documents
• Personnel properly trained
• Work environment maintained
• Non-conformances & complaints addressed
• Corrective and preventive actions
• Equipment maintained
• Quarantining of product before release
• Product release, analysis of products
• Conformance to specifications
cGMP – ISO 9001: a comparison

83. 8383
cGMP
• Specific for pharma (manufacturing
of medicines)
• A legal requirement
• Product quality focused:
• safe, pure & effective
• Detailed requirements:
• what – not how
• Narrow scope: production & QC
• Quality unit
ISO 9001
• Generic – for all types of
organsiations
• Voluntary – industry practice
• Business focussed
• customer satisfaction
• Not as detailed as GMP
requirements
• Wide scope: entire organisation
• Management representative
Differences
cGMP – ISO 9001: comparison

84. 8484
Conclusion
• It is not either ISO or GMP – it can be both
• GMP operations benefit from adding ISO 9001 required measurement,
review and customer satisfactions programs
• IOS companies benefit from GMP’s system control requirements and
from the standard to demonstrate “safety, strength, quality and purity”
of the product
• Demonstrate Quality Oversight
• Harmonization – ICH
Quality Management System(s)

85. 8585
Questions?
QUESTIONS

86. 8686
Further information
Luc Marivoet
Senior Consultant QM / Engineering Services
luc.marivoet@pauwelsconsulting.com
09 – 324 70 80
Luc Huybreghts
Senior Consultant QA & Compliance
luc.huybreghts@pauwelsconsulting.com
09 – 324 70 80

87. Quality Management Systems (QMS)
Luc Marivoet & Luc Huybreghts Antwerp, March 30 , 2017