Documenti di Didattica
Documenti di Professioni
Documenti di Cultura
Groups EWG
( ) • Chemical and pharmaceutical QA
• Safety
• Efficacy
• Clinical studies
in human subject
• Multidisciplinary
General topics
Manufacture of sterile medicines – Advanced workshop for SFDA GMP inspectors
Nanjing, November 2009
6|
The ICH process
Opportunities to impact
risk using quality risk
Design management
Process
Materials Manufacturing
Facilities
Distribution
Patient
GLP Safety
GCP Efficacy
GMP/GDP ICH Q9
Quality
Manufacture of sterile medicines – Advanced workshop for SFDA GMP inspectors
Nanjing, November 2009
10 |
Managing the risk of drug product use
Medication or Device
Known Side Effects Product Defects
Error
Avoidable Unavoidable
ICH Q9
Efficacy Quality
Safety Preventable
Adverse
Events
Unexpected Injury or
Consequences Death
Public Health
Manufacture
Source: of sterile
basic modelmedicines
adapted –from
Advanced workshopManaging
FDA (1999). for SFDA GMP inspectors
the Risks from Medical Product Use.
Nanjing, November 2009
11 |
ICH Regulators:
– FDA: New paradigm with the 21st Century
GMP initiative
– EMEA: Revised EU directives
– MHLW: Revised Japanese law (rPAL)
“risk-based”
concepts and
principles
Q8 Q9 Q10
Manufacture of sterile medicines – Advanced workshop for SFDA GMP inspectors
Nanjing, November 2009
13 |
Pharmaceutical Development (Q8)
Changed Past: Data transfer / Variable output
Paradigm Present: Knowledge transfer / Science based /
Consistent output
High
Q10 Pharm. Quality Systems
Using Q9
Quality Risk
Management
Low Q8 Pharmaceutical Development
principles
Low High
Manufacture of sterile medicines – Advanced workshop for SFDA GMP inspectors
Nanjing, November 2009
15 |
Opportunities to impact
risk using quality risk
Design management Q9
Process
Materials Manufacturing
Facilities
Distribution
Patient
Q8 Q10
Manufacture of sterile medicines – Advanced workshop for SFDA GMP inspectors
Nanjing, November 2009
16 |
Manufacture of sterile medicines – Advanced workshop for SFDA GMP inspectors
Nanjing, November 2009
17 |
Process
Understanding Process Process
Understanding Understanding
CMC CMC
regulatory
regulatory
Oversight CMC CMC
regulatory
(Submission)
oversight regulatory
Oversight
(Submission)
oversight CMC
regulatory
oversight
cGMPcGMP
regulatory
regulatory
oversight Q8 cGMPcGMP
regulatory
regulatory
oversight Q10 cGMP
regulatory
(Inspection)
oversight
& (Inspections)
oversight
& oversight
Company’s
Quality system
Q9 Company’s Q9 Company’s
Quality system
Quality system
Post
Approval
approval
Change Continuous
PAC to
PAC to Improvement
change
(PAC)
Continuous
Continuous
Risk
Ris Improvement Risk
Improvement
(perceived
(P/R)& real) Risk
k
Manufacture of sterile medicines – Advanced workshop for SFDA GMP inspectors
Nanjing, November 2009
18 |
What does it mean?
What is it worth?
Provide assurance
– Risks are adequately managed
– Compliance to external and internal requirements
Increasing
external Growing
requirements complexity
and scope of risks
?
for best practice,
transparency and
compliance • Globalisation
• Public / Community
“Multinational”
• Governments
• Multi-factor approaches
• Regulators
• Regulatory expectations
• Patients Investors /
• Acceptance of
Creditors
Increasing risk and uncertainty
• Documentation
efforts and costs • Projects
for sustainability • Systems
• Interfaces
Master complexity
Convert data into knowledge
e.g. by using methodology and tools
Manufacture of sterile medicines – Advanced workshop for SFDA GMP inspectors
Nanjing, November 2009
23 |
Different meaning of risk
Individual
– Risk is a cognitive and emotional response to expected
loss
Technicians
Risk is usually based on the expected value of the
conditional probability of the event occurring multiplied by
the consequences of the event given that it has occurred
ICH Q9
– Combination of the probability of occurrence of harm
and
the severity of that harm
Manufacture of sterile medicines – Advanced workshop for SFDA GMP inspectors
Nanjing, November 2009
24 |
Organizations might use many different meanings of risk
– Depending on the type of risk management program
for
evaluating risks
m
ed
iu
m
lo
w
ri s severity
k
Manufacture of sterile medicines – Advanced workshop for SFDA GMP inspectors
Nanjing, November 2009
27 |
A picture of the life cycle
Refers to
Refers to
past today future time
ICH Q9
Existing a s ed
internal is k-b ach
ng
R pro r
s
Where ap
al risk
documentation de
residu ble
n
to be in i
se me
system n s Q9
EA ta
future?
Co CH
ba le
(Mission, Policy)
s
k- Imp
I
l
too
M
What to do?
e.g. F
fic
s
(e.g. Directives)
ris
ple
list of
us Exam
How to do?
sp
(e.g. Guidelines)
ing
Detailed instructions Records
(e.g. Standard Operating Procedures)
hazard
Failure
- technical breakdown System defect
- human breakdown - not detected
- extrinsic effect - insufficiently prevented
- emerges by degree
Time today
RISK: For a given severity of risk event, what are the chances
(probability) of exceeding the USL in the next period of time?
Uncertainty
Time today
Uncertainty
uncertainty Hazard
Hazard
may may not
cause harm cause harm
Manage risks
in relation to
probability &
severity
Hazard
is less likely to
cause harm
Manufacture of sterile medicines – Advanced workshop for SFDA GMP inspectors
Nanjing, November 2009
35 |
Quality Degree to which a set
of inherent properties
of a product, system or process
fulfills requirements
Management
Systematic process for the assessment,
control, communication and review
of risks to the quality of the drug (medicinal)
QRM product across the product lifecycle
Manufacture of sterile medicines – Advanced workshop for SFDA GMP inspectors ICH Q9
Nanjing, November 2009
36 |
HAS NOT QRM ALREADY
BEEN IMPLEMENTED
•
Yes, however we need to firm-up and set the priorities in relation to
risks. We need to know…
– How good is QRM compliance and decision making?
– To what extent QRM has to be implemented or formalised?
Risk Assessment
Risk Identification
Risk Analysis
Risk Evaluation
unacceptable
Risk Reduction
Risk Acceptance
Risk Review
Review Events
Hiding risks
Using QRM
Gain experience
Analyse root cause: (Risk of) Failure ?
Continuous Quality Manufacture
improvement Risk for market
Managem
ent
Improve it (QRM) Do, what you say
Update Approval
documentation
Say, what you do
Manufacture of sterile medicines – Advanced workshop for SFDA GMP inspectors
Nanjing, November 2009
45 |
Definitions of “Compliance”:
– Conformity in fulfilling official requirements
– The act or process of complying to a
desire, demand, or proposal or to coercion
– A disposition to yield to others
Use
“science-based” and
“risk-based” behavior
Sharing information
From tick-box
approach for compliance
towards
systematic
risk-based thinking
Manufacture of sterile medicines – Advanced workshop for SFDA GMP inspectors
Nanjing, November 2009
54 |
Change in behaviour
Doing things,
that do not matter
for the patient
Manufacture of sterile medicines – Advanced workshop for SFDA GMP inspectors
Nanjing, November 2009
55 |
Integration of QRM
into existing systems
and
regulatory processes
will take time, trust and
communication
Manufacture of sterile medicines – Advanced workshop for SFDA GMP inspectors
Nanjing, November 2009
56 |