Professional Documents
Culture Documents
Barry O Donovan Novartis (Compatibility Mode)
Barry O Donovan Novartis (Compatibility Mode)
Road map/milestones/documentation
Legend
Risk Assessmts,
Protocols &
reports
Peer Reviews
DS synthesis
CHAD/Chem
CHAD/
Chem Ops
D3
CSP
sPOC
ISA
POC
CSP
PCM1
PCM2
Prot. adequate
P2
P1
Synthesis
Strategy I
Synthesis
Strategy II
Quality
Review I
PCM3
Prototype
Exp.Report
Exp.Report
Process Challenge
Quality
Review III
Quality
Review II
Experiments/Batches Confirmation
Exp.Report
Process Challenge
QRA protocol
Peer review assessment
Launch
Synthesis
Strategy III
Experiments
Exp.Report
Sub
Process
Evaluation
Meeting
PEM
Ph IIb readout
Ph IIa readout
Exp.Report
Process Challenge
QRA report
Process Eval/Challenge
Exp.Report
QRA update
Launch
Risk Management
tools
Example parameters
Parameter
Set
Variation
point
+/&
, P, M
accept
DoE
able Informatio
range
n
1.2.2
1.38e
q.
Quant. B2
2.0
Rating of Effect
crit = c
uncrit=u
1.5
1.25
1.0
1.0
1.25
1.5
2.0
Reference to
literature or
experiment
Comments
Example parameters
5.7
Slow formation of the propylester (2.4% after 56h at 6090C); during crystallization afterwards the byproduct is
eliminated completely into the mother liquor.
Time and t = ?h
Temp.
during
evap. of B3
6.5 / 7.1
60C
90C
Maximal
Temp. of
B5- and B6solutions
8.1
Seed
temperatur
e
8.2.
B10
Type of
seeds
8.3
Amount of
seeds for
B5
0.3%
C/U
16.7% 522-05 (
60C
Dissolution of seeds
B10 + 522-05
(50%)
E-47312Bix09028 K1a
(comp. to K1b)
0%
E-46213Bix09011 A
0.05%
0.15%
0.1%
U/C
0.3%
1%
10%
Risk Management
tools
Methodological
OVAT
- Principally One variable at the time strategy (Although DoE is not excluded)
- No or few information on parameters interaction
Risk Management
tools
Current QRA
New QRA
History of Process
CER
Synthesis Scheme
LV/BV
LV/BV
LV/BV
Chemical production
Control strategy
CER
QRA
Summary
Design space
Follow-up action
10 | Quality Risk Assessment | Barry O Donovan | 11-Nov-2010 | Business Use Only
Risk Management
tools
QRA summary
New QRA is a tool:
Systematic approach based on:
- Science (ICH Q8)
- Risk assessment (ICH Q9)
Living stand-alone document which gather key information/data and avoid later on
difficult data mining
Back-up
Peer Review
concept
Probability of
Occurrence
Severity [Description
of Impact in case of
Occurrence]
1.1
2.1
Risk Categorization
Regulatory
Quality
Non-Technical Risks
Timelines /
Who