Pfizer Grange Castle –
Product Change Over
Ronan Rafferty
Multi-product Project - Downstream Operations Lead
Pfizer
22 May 2014
Current & Future State
Current:
Single Product Capability - utilising specific single
product process steps.
Future:
Facility designed to produce therapeutic
fusion proteins / MAb’s from mammalian cell
lines
Multiple Product Capability ranging from
utilising adaptable and scalable platform
process steps.
2
Level 1 Layout
Cell Culture
New
Harvest
Current
Purification
New Harvest and Initial
Purification
3
Level 2 Layout
New Final
Purification
Cell Culture
Lower Buffer Prep
Inoc. Lab
Upper Media Prep
New Intermediate
Purification
4
Level 3 Layout
Large Equipment Wash Area
(LEWA)
+ Autoclave
Upper Buffer Prep
Upper Media Prep
Expanded Buffer Prep.
5
Facility Overview
Area
Grade
Concurrent Manufacturing
Room 1
Inoculation Lab
Grade C
Yes
Room 2
Bioreactors
CNC
Yes
Room 3
Harvest
Purification 1
Column Packing
Purification 2
Column Packing
Purification 3
CNC
No
Grade D
No
Grade D
Yes
Grade D
No
Room 4
Room 5
Room 6
6
Multi Product Documentation Road Map
7
Key Outputs from Multiproduct
Risk Assessment
Implement
segregation
controls
Controls for
open activities
and breaches to
functionally
closed systems
Create line
clearance
procedures
Multi
Product
Risk
Assessment
Update
Personnel,
material and
waste flows
Complete
closure analysis
Implement
Visual
management
system for
product soil
segregation
8
Lean Product Change Over
“great ideas do not always come fully formed”
9
Journey to Lean Changeover
3 Phases of Program
Fixed Equipment
- Cleaning
Validation Samples
- Verification
samples for PCO
-C/O of
membranes &
resins
-Elastomer C/O?
Small Parts
Phase 1
- CV Samples
-Segregation of
Product contact
parts
- Separate loads
- Verification
samples for PCO
(at end of
campaign)
Phase 2
- Verification
samples for PCO
-C/O of membranes
& resins
-Selected Elastomer
C/O?
-NO Segregation of
product contact
parts
- Mixed loads
- Verification
samples for PCO
Phase 3
- C/O of
membranes &
resins
Product Changeover – Phase 3
Robust Cleaning
Validation &
Data from
Cleaning
Verification
No segregation
of product
contact parts
C/O of
membranes,
resins, multiuse
filters
No verification
samples
required
Journey to Phase 3
Robust Segregation and PCO
procedures
Completion of Closure Analysis
SMED analysis of PCO
Elastomer Lifetime Study &
Cleanability Study
Extensive cleaning history
12
Key Decisions
What level of cleaning verification is considered robust in order to move Phase 3 where
cleaning verification is no longer required?
1.
Where Product B is considered not to be worst case V Product A – what level of cleaning
verification is considered appropriate on introduction of Product B?
2.
Where microbial sampling is completed for cleaning validation – in what situations can this
be removed for PCO cleaning verification?
3.
Mixed loads for product contact parts – cleaning validation will be completed from Product
A to B. What are the challenges and potential pitfalls?
4.
Elastomer Assessment: What approach should be used to determine if elastomer
changeout needs to be performed for PCO?
5.
13
Backup Slides
14