1. GDP Quality Management Risk Based Approach
Frank Peeters, Ph.D.
GDP Responsible Person Raes Pharmaceutical Logistics
Senior Consultant, Tobeas bvba
Nimfenstraat 1, B-2800 Mechelen

2. Overview of GDP Regulations

3. Globalized Production: Potential Risk

4. Good Distribution Practices The New EU Regulation
EU GDP Act - Guidlines of 7 March 2013 on Good Distribution Practice of Medicinal Products for Human Use (2013/C 68/01)
 5 Nov /C 343/01
Although the act specifically states products for Human use, the authorities and pharma clients extend it to veterinary products and IMP’s (investigational medicinal products)

5. The difference between GDP Compliance and Certification
Products are stored and distributed in a GDP-compliant manner. This ensures control over the distribution chain and consequently maintains the quality and integrity of medicinal products
 All storage & distribution activities require GDP compliance
Certain activities require certification by the competent authorities, while others are only controlled by the marketing authorization holders (MAH) themselves
 Only storage activities currently require a GDP license
Warehousing
Storage:
Months
Storage
in view of
Transport
Days -Weeks
Cross
Docking
Storage:
Hours
Transport
GDP license required
Exempt of GDP license

6. EU GDP Act 2013/C 343/01 Effective 5 November 2013
1. Quality Management System
2. Personnel
3. Premises and Equipment
4. Documentation
5. Operations
6. Complaints, Returns, Suspected Falsified Medicinal Products and Medicinal Product Recalls
7. Outsources Activities
8. Self-Inspection
9. Transportation
10. Specific Provisions for Brokers
New in the regulation:
Risk Based Approach

7. Risk Based Approach: where does it apply for me?

8. “Risk” in the GDP Regulation:
23 times

9. “Risk” in the GDP Regulation:
23 times

10. “Risk” in the GDP Regulation:
23 times

11. “Risk” in the GDP Regulation:
23 times

12. Risk Management
Avoid all risks that can have an impact on the product quality and on patient safety
 Risk Management:
Don’t try to do everything
Focus on the high risks
The residual risk is “ALARP”: As Low As Reasonably Possible

13. How to Comply? Risk Management Guidelines
Medicinal Products:
Eurdralex Annex 20 – Quality Risk Management
Equals ICH Q9 – Quality Risk Management
adopted 2005, in operation March 2008
Tripartite: EU, US & Japan
FDA initiative, Pharmaceutical cGMPs for the 21st Century A Risk-Based Approach – Sep 2004
Medical Devices:
ISO 14791:2000  2007

14. Link ICH Q8 (Pharmaceutical Development) with ICH Q10 (Pharmaceutical Quality Sytem)

15. Definition of Risk
IEC « The likelihood of a specific hazardous event occuring within a specific period or in specific circumstances »
IEEE « A measure of the probability and severity of undesired effects. Often taken as the simple product of probability and consequence »
ISO Guide 51 « Combination of probability of harm and severity of harm »

16. Definition of Risk
IEC « The likelihood of a specific hazardous event occuring within a specific period or in specific circumstances »
IEEE « A measure of the probability and severity of undesired effects. Often taken as the simple product of probability and consequence »
ISO Guide 51 « Combination of probability of harm and severity of harm»

22. Different Risk Classes
GDP Risk (Product)
Business Risk
Relating to the product (eg unavailability)
Relating to the company (financial, reputation…)
Safety risk (Safety Health Environment)
Cosmetic Impact, Comfort

23. Risk Management Tools (see ICH Q9)
Basic risk management facilitation methods
questionnaires
check sheets
flowcharts
Risk ranking and filtering
Failure Mode Effects Analysis (FMEA)
Failure Mode, Effects and Criticality Analysis (FMECA)
Hazard Analysis and Critical Control Points (HACCP)
Fault Tree Analysis (FTA)
Hazard Operability Analysis (HAZOP)
Preliminary Hazard Analysis (PHA)
Supporting statistical tools

24. Top-down Risk Assessment: Risk Ranking
Example: GDP criticality on equipment:
Which Areas are GDP critical (eg Pharmaceutical vs Food)
Which Systems are GDP critical
Which Hardwore & Software Components are GDP critical
Which User Requirements and Functions are GDP critical

25. Intermezzo: What are GDP Critical Systems?
which maintain the correct temperature conditions
whereby there is a risk for contamination or mixup
whereby an adequate turnover is assured (FEFO)
that assure a safe and secure storage including during transportation
that assure the delivery of the right products to the right addressee
to perform planning tasks that may have impact a on timely delivery
that are involved in tracing of faulty products
that are involved in recall processes.

26. Top-down Risk Assessment: Risk Ranking
Example: GDP criticality on equipment:
Which Areas are GDP critical (eg Pharmaceutical vs Food)
Which Systems are GDP critical
Which Hardwore & Software Components are GDP critical
Which User Requirements and Functions are GDP critical

27. Risk Classification

28. Prioritization based on risk
Period Period Period Period 4

29. Risk Quantification

30. FMEA Tool (prior to actions)

31. FMEA tool (after actions)

32. Risc Reduction Strategy
Avoid
Reduce
Low Medium High
Probability
Accept
Low Medium High Risc

33. Risk Acceptance After every Risk Analysis: Is your Risk Reduced?
Take a ‘Time Out”
Ask yourself: DOES THIS FEEL RIGHT?
Professionally
Morally
Ethically
Is your Risk Reduced?
Mitigation of the Severity?
Reduction of the Probability?
Increase of the Detectability?
 and then RISK ACCEPTANCE

34. The “Swiss Cheese” Approach: Building in safety measures

35. RISK REDUCTION STRATEGY
Conclusion:
RISK BASED APPROACH =
RISK KNOWLEDGE +
RISK REDUCTION STRATEGY
RISK BASED DECISION

36. Risk Based Decision Making
Hard Data Soft Data
(Facts)
Experience
Hard Data + Soft Data + Experience = JUDGEMENT

40. Decision Making: Facts
Risk accompanies every decision
You will never know all the facts – some assumptions must be made
Most decisions are made at the emotional level (does it feel right?)
Our brain is wired for speed, not for accuracy
Beware of patterns – never confuse fact with assumption
The decision making environment has a big impact
Stress kills effective decision making
Time is always your enemy

41. Understand the “problem”
Obtain Hard Data and information:
The WHO
The WHAT
The WHY
The HOW
The WHEN

42. Understand the “problem”
Obtain Hard Data and information:
The WHO
The WHAT
The WHY (ask 5 times WHY)
The HOW
The WHEN
BUT AVOID PARALYSIS BY ANALYSIS

43. Remove Risk Increasing Factors
Structural Causes
Inconsistent process, Unreliable equipment, Poor design/layout, Failure to standardize, Workload, Fatigue, Time pressure, Interruptions
Prevention
Workspace (Ergonomics)
Lighting, Noise, Workflow not logical, Inadequate segregation of areas, Discomfort, Duration of Tasks, Inadequate maintenance of premises, Temperature too hot/cold, Visual distractions, Smells & pollutants
Environmental Causes
Cultural & Organization: Poor communication, Hierarchy, Bureaucratic, KPI’s encourage Under-reporting
Accountability

44. Remove Risk Increasing Factors
Process Related Causes
Unclear Procedures, Over dependency on memory, Relying on human vision, Too many checks and too often, Only see what you expect
Prevention
Information Related Causes
Too many documents, too complex, inaccurate or not suited for the purpose
Latest versions of instructions not available
Inappropriate use of assumptions, only verbal communication
Communication not given to all staff
Staff who is using the documentation does not consult it
Staff doesn’t understand the risk for the patient
Individual (Physical, Mental)
Tiredness, Illness, Hangovers & Drug abuse

45. Typical Quality Risk Management Process
Initiate
Quality Risk Management
Assessment
Output/result of the
Quality Risk Management Process
Risk Identification
Risk Reduction
Risk Evaluation
Risk Analysis
Risk Acceptance
Review Events
Unacceptable
Risk
Control
Risk Communication
Risk Management Tools
Review
Last loop from review to control is typically used troughout the lifecycle of a product.
Interactive Round Table Quality Risk Management
November 13, 2008