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Outline
Xcellerex
Xcellerex
More
biological
variables
Xcellerex
Greater
need for
PAT
Future:
Xcellerex
Fermentation
Purification
Formulation
Fill Finish
Xcellerex
Purpose
Present
Future
Control
product quality
Cell growth
Cell viability
Metabolic parameters
(dO2, pH, glucose)
API content
API quality
Impurities
Bioburden & viruses
Process parameters
(OD, pH, Flow rate,
Conductivity)
API concentration
API quality
Impurity clearance
Bioburden & viruses
API concentration
Environment
Fill volume
API quality
Content uniformity
Excipient uniformity
Impurity levels
Sterility
Ensure
biosafety
Control product
quality
Ensure impurity
removal
Ensure biosafety
Ensure product
Ensure uniformity
Ensure safety
Benefit
Optimized process from start
of clinical manufacturing
Examine more parameters in
less time
Process Analytics
Product Quality microarray
glycosylation analysis
Process control via noninvasive sensors pH, DO2,
optical density, IR
On-line environmental
monitoring non-viable
particulates
Xcellerex
Non-invasive monitoring of
process parameters
Real-time assessment of
environmental control
Benefit
Controlled environment
modules
Operator separation
Minimize environmental
contamination
Increase flexibility
Disposables
Minimize cross-contamination
Xcellerex
Knowledge Management
eFactory
MyProject
secure portal
Proj. Mgmnt
Supply Ops
Quality Control
Finance
Reg Affairs
Contract
Vendors
Test Methods
Contract
FDA contact
Phases
Mat. flow
Sample status
Invoices
IND outlines
Your project
Inventory
Trending
Accruals
Submissions
Batch data
Doc Approvals
Data
Lot release
Experiments
Trending
Doc Revisions
Protocols
Exceptions
Methods
BPRs
Change control
Methods
Deviations
PD
Mfg
QA Documentation
Quality
QA Release
Xcellerex
Bestcondition:1.9MM
cells/ml
Cellsstill94%viable!
Fractional
FactorialWells
CenterPoint
Wells
SigmaMedium
Wells
256
20
12
AverageOD600
0.281
0.305
0.323
CVofOD600,
avg
3.7%
3.6%
7.6%
Approximate
CellDensityat
averageOD600
(MMcells/ml)
1.2
1.5
1.7
CVbasedon
approximate
celldensity,MM
cells/ml
10.2%
8.7%
17.0%
Numberof
Wells
NormalMHB~0.8MM
cells/ml
Xcellerex
Xcellerex
Step 1
Step 2
Step 3
Step 4
Xcellerex
Xcellerex
28-Aug-02 21:04
28-Aug-02 17:08
28-Aug-02 13:12
28-Aug-02 09:15
28-Aug-02 05:10
28-Aug-02 01:11
27-Aug-02 21:20
27-Aug-02 17:30
27-Aug-02 13:33
27-Aug-02 09:37
27-Aug-02 05:41
27-Aug-02 01:44
26-Aug-02 21:48
26-Aug-02 17:52
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Summary
Impact of PAT
Measure product quality in process stream
Increased understand of process product quality
relationship
Continual process monitoring obviates need for process
validation
Enables science-based decision making in manufacturing
Reduces batch release time, increases plant capacity
Lower manufacturing risk and COGS
Can be a very cost effective investment
Xcellerex
Opportunity
PA
Process Knowledge
Future
Present
Efficiency