quality management systems in different industries - from iso 9001 to cgxp
TRANSCRIPT
Quality Management Systems (QMS)
Luc Marivoet & Luc Huybreghts Antwerp, March 30 , 2017
22
0 Presented by
Luc Marivoet, Senior Consultant QM / Engineering Services Luc Huybreghts, Senior Consultant QA & Compliance
LUC²Lecturers Using Craftsmanship in QMS
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
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1 A brief history of Quality
How it startedHandcrafting
Industrial RevolutionMass production
Deming, Juran and JapanImproving organizational process
World War IISampling for inspection
The American ResponseTotal Quality Management
Late 20th CenturyQuality Management System
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
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2 Quality Management Systems
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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
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3 Quality Management System ISO 9001
Historical timeline
ISO9001:1987
Procedures
ISO9001:1994
Say what you do
& do what you say
ISO9001:2000
Process Approach
& PDCA
ISO9001:2008
Process Approach
& PDCA
ISO9001:2015
Context
Risk / Opportunity
99
Normative reference• QMS standards for which ISO 9001 is a normative reference:
3 Quality Management System ISO 9001
1010
ISO 9000 series
3 Quality Management System ISO 9001
ISO 9000Quality
Management Systems
–Fundamentals and
vocabulary
ISO 9001Quality
Management Systems
–Requirements
ISO/TS 9002Quality
Management Systems
–Guidelines for the
application ofISO 9001:2015
1111
3 Quality Management System ISO 9001
Plug-in model
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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
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5 Key Requirements of ISO 9001
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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
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4. Context of the organization• Understanding the organization and its context.
5 Key Requirements of ISO 9001
POLI
TICA
LTE
CHN
OLO
GYM
ARKE
T
RESO
URCE
SHU
MAN
ASP
ECTS
OPE
RATI
ON
AL
STRATEGY
EXTERNAL ISSUES INTERNAL ISSUES
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4. Context of the organization• Understanding the organization and its context.
5 Key Requirements of ISO 9001
STRENGTH WEAKNESS
OPPORTUNITY THREAT
Inte
rnEx
tern
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4. Context of the organization• Understanding the needs and expectations of interested parties.
5 Key Requirements of ISO 9001
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4. Context of the organization• Determining the scope of the quality management system.
5 Key Requirements of ISO 9001
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4. Context of the organization• Quality management system and its processes.
5 Key Requirements of ISO 9001
2020
4. Context of the organization• Quality management system and its processes.
5 Key Requirements of ISO 9001
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5. Leadership• Leadership and commitment. • Policy.• Organizational roles, responsibilities and authorities.
5 Key Requirements of ISO 9001
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5. Leadership• Leadership and commitment.
• Policy.
• Organizational roles, responsibilities and authorities.
5 Key Requirements of ISO 9001
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6. Planning• Actions to address risks and opportunities. • Quality objectives and planning to achieve them.• Planning of changes.
5 Key Requirements of ISO 9001
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6. Planning• Actions to address risks and opportunities.
5 Key Requirements of ISO 9001
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6. Planning• Actions to address risks and opportunities.
5 Key Requirements of ISO 9001
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6. Planning• Quality objectives and planning to achieve them.
5 Key Requirements of ISO 9001
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6. Planning• Quality objectives and planning to achieve them.
5 Key Requirements of ISO 9001
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6. Planning• Planning of changes.
5 Key Requirements of ISO 9001
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7. Support• Resources. • Competence.• Awareness.• Communication.• Documented information.
5 Key Requirements of ISO 9001
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7. Support• Resources.
5 Key Requirements of ISO 9001
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7. Support• Competence.
5 Key Requirements of ISO 9001
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7. Support• Competence.
5 Key Requirements of ISO 9001
3333
7. Support• Awareness.
5 Key Requirements of ISO 9001
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7. Support• Communication.
5 Key Requirements of ISO 9001
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7. Support• Communication.
5 Key Requirements of ISO 9001
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7. Support• Documented information.
5 Key Requirements of ISO 9001
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7. Support• Documented information.
5 Key Requirements of ISO 9001
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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
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8. Operation• Operational planning and control.
5 Key Requirements of ISO 9001
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8. Operation• Operational planning and control.
5 Key Requirements of ISO 9001
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8. Operation• Requirements for products and services.
5 Key Requirements of ISO 9001
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8. Operation• Requirements for products and services.
5 Key Requirements of ISO 9001
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8. Operation• Design and development of products and services.
5 Key Requirements of ISO 9001
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8. Operation• Design and development of products and services.
5 Key Requirements of ISO 9001
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8. Operation• Control of externally provided processes, products and services.
5 Key Requirements of ISO 9001
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8. Operation• Production and service provision.
• Release of products and services.
• Control of nonconforming outputs.
5 Key Requirements of ISO 9001
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9. Performance evaluation• Monitoring, measurement, analysis and evaluation. • Internal audit.• Management review.
5 Key Requirements of ISO 9001
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9. Performance evaluation• Monitoring, measurement, analysis and evaluation.
5 Key Requirements of ISO 9001
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9. Performance evaluation• Monitoring, measurement, analysis and evaluation.
5 Key Requirements of ISO 9001
CONFORM ISO 10004
5050
9. Performance evaluation• Internal audit.
5 Key Requirements of ISO 9001
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9. Performance evaluation• Internal audit.
5 Key Requirements of ISO 9001
CONFORM ISO 19011
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9. Performance evaluation• Management review.
5 Key Requirements of ISO 9001
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10. Improvement• Nonconformity and corrective action. • Continual improvement.
5 Key Requirements of ISO 9001
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10. Improvement• Nonconformity and corrective action.
5 Key Requirements of ISO 9001
NONCONFORMITY CORRECTION
CORRECTIVE ACTION ACTION TO ADDRESS THE RISK
5555
10. Improvement• Continual improvement.
5 Key Requirements of ISO 9001
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?QUESTIONS
6 Questions
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
R Quality Management Systems
Different approaches• Process-oriented: ISO 9001• Product-oriented: cGMP
5858
R Quality Management Systems
5959
Good Manufaturing Practices• What – why • Historical overview• Structure
• Eudralex• FDA
• Evolution – latest trends• Dangers & pittfalls• Business enabler
Comparison & relation with ISO
Conclusion
cGMP
6060
cGMP
Do you trust the pill you took today ?
The Matrix
6161
cGMP
Quality should be built into the productand testing alone cannot be relied on
to ensure product quality.
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cGMP
Quality & Compliance
ManagerThe 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
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What• current Good Manufacturing Practices • Pharmaceutical industry – life-sciences• It is the LAW – regulatory authorities
Belgium: FAGGBrazil: ANVISA EU: EMA UK: MHRAUSA: FDA
cGMP
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IndiaIsrael
Biologics Control Act
Federal Food,Drug and Cosmetic Act
Guidance Documents
ChineseMilk Scandal
Tylenol
Thalidomide
The Pure Food and Drug Act
Public Health Services Act
19021906
19381944
19621979
19821998
20082013
UpdateEudralexChapter 1
cGMP - timeline
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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 GMPGCP
GMPGDP
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
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cGxP – general
Combination of regulations and guidelines
Regulatory Authorities: Argentina Egypt RomaniaAustralia FDA Saudi Arabia Austria ICH SingaporeANVISA India S. AfricaCanada Ireland S. KoreaChina Italy UAECzech Rep. Malaysia Venezuela EU MexicoMHRA
Guidance standardsICH International Conference of HarmonisationPDA Parenteral Drug AssociationPIC/S Pharmaceutical Inspection Convention
Mandatory standardsWHO – World Health Organization
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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
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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
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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
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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 Fileo Q9 Quality Risk Managemento Q10 Guidance on Pharmaceutical Quality Systemo MRA Batch Certificate
cGMP
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
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Structure GMP (FDA Code of Federal Regulations)Guidance Documents – Guidance for industryImplement modern quality systems – risk management
cGMP
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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
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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
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Management responsibilities
PQS elements: process performance – product quality monitoring system – CAPA system – Change Control system management review system
Enablers: knowledge management – quality risk management
Pharmaceuticaldevelopment
TechnologyTransfer
Commercialmanufacturing
Productdiscontinuation
cGxPInvestigational
products
cGMP - PQS
Pharmaceutical Quality System
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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
7878
2. Quality function is detached from operations
I know this is a compliant procedure. I used it at my last companyYou 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
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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 ASAPA 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
8080
4. Large scale cGMP performance improvement
The CAPA implementation efforts are going nowhere. Manufacturing department says their priority is the production scheduleWe 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
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
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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
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
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)
8585
Questions?
?QUESTIONS
8686
Further information
Luc MarivoetSenior Consultant QM / Engineering Services
[email protected] – 324 70 80
Luc HuybreghtsSenior Consultant QA & Compliance
[email protected] – 324 70 80
Quality Management Systems (QMS)
Luc Marivoet & Luc Huybreghts Antwerp, March 30 , 2017