Filling line & Lyo Interface
(one Isolated system)
‘Case Study’
By
Ben Riepe
608-562-7735
briepe@walkerbarrier.com
www.walkerbarrier.com
Discussion Points
Key design steps of a custom capital
Isolator equipment project
Dealing with existing equipment for
design interface
Fundamentals of Project Management
that drive a successful solution
- IE) design review approval process &
communication of milestones
Design Criteria to set the stage for this particular
application. (note: criteria is different for every
custom application within Pharma facility
process)
Do you have a cycle development study involving injectables
and/or vaccines?
Are you testing phase1 toxicity levels (small runs)?
Do you want expanded capabilities for phase3 using a Lyo?
Are you limited on space?
Do you need to contend with any existing equipment?
Step1: Define the room layout – provided by
client or A&E Firm
Step2: Concept Development (Layout & Flow)
Biggest Constraints
• The room layout is fixed (entrance on left side)
• The transfer Isolators are existing (this locks the size
of these systems & vial capacity)
Existing Transfer Isolator
• This is a turbulent
flow system.
• Mobile design
(moves from room to
room)
•Decontaminated with
a remote vHP
generator
From concept to details
Feasibility of Isolation HVAC around layout
What are the necessary filling line speeds & lyo capacity
How does one transfer vials from filler to lyo
What is the max filler speed needed? 80 vials/min (vol. 10ml)
What is the max lyo capacity needed? 2000 vials
How to transfer from Filler to Lyo under a
sterile environment?
Common layout in Pharma facilities is to have the Filler & Lyo
remote from each other
Requires either an AGV ‘automatic guided vehicle’ or a sterile
UAF transfer chamber
Solution for this application: Half-suit
Half-suit photo example
Half-suit layout placed in concept dwg
Half-suit (circle) Plan View layout concept
Isolated Process (infeed)
Depyrogenation Oven
Interface Isolator to presterilize empty vials before
transfer from 3-glove to Filler
Process doesn’t stop with
just the filling, there is a
chain of Isolation required in
many to most cases.
Ie) formulation, autoclave,
oven, sterility testing.
Outfeed Sterility Testing
Samples are taken from
the Filler to a dedicated
Sterility Testing Isolator
as well.
Every piece of Isolated
equipment must go
through the same design
criteria to determine it’s
fit, placement, and need.
Viable & Non-Viable Monitoring
Isoprobes for both
viable and non-viable
monitoring are located
inside the Isolator next
to the filling head
There is (1) non-viable
particulate monitoring
probe
There are (4) viable
monitoring probes
within the Isolator
Note: there is no
monitoring in the
transfer units being that
these came direct from
a depro oven with
sterilized transfer
Viable & Non-Viable Monitoring
continued.
Sample is drawing
thru plate in Isolator,
and media is located
outside the Isolator.
Easier to have
media outside as
you don’t have to
manipulate pieces
inside the Isolator
and disturb the
environment &
media change outs
are quick and simple
Mock Up Construction
Mock ups are an
important part of isolator
design.
Construction is of wood
and often uses actual
components.
Operators can perform
ergonomic studies
before final design.
Mock-up Preparations
Side view showing HVAC stack-up, port placement, & filler layout
Mock-up Review
Purpose:
- define ergonomic overlap to process
- confirm integration & equipment fit
- gives a visual of the process
Mock-up Ergonomic Testing
Mock-up (including internal filler &
gloveports for ergo placement)
Refine technical details into a 3D print
Approval Process
Involves a technical review that targets
Mechanical Interfaces & Mock-up cross reference
Controls layout and communication
Understanding of utility location & requirements
Process flow cross reference
Approval to Fabricate from authorized figure @
Client site. (Typically signed approval of a
functional and/or design specification, P&ID, and
CAD drawing)
3D cross sectioning
Positioning is
placed from
concept to mockup to 3D layout.
3D prints not only
give good visual
understanding of
the design for the
customer, it is
also used as the
basis for the
details prints for
fabrication.
3D layout cross section
Process flow
with
integrated
equipment
placed into
the shell
Value added:
to client
assist in
approvals
Value added:
to vendor
alleviate major
interferences
Approval Process - continued
Need the key decision makers in the capital
approval process from start to finish
Good ‘team’ decision maker requirements
‘Process Engineer’ Full understanding of client process
‘Project Lead’ Client funding & timing constraints
‘Validation Engineer’ – What documentation & testing is
required.
‘Safety’ – Has a Haz OP been executed pre-approval
Build Process
The fabrication of the shell: view of the interface for the Lyo
Once system
is vendor
manufacturin
g, it is
extremely
difficult to
change the
design.
At this point it
is in the
hands of
vendor
Project
Management
to drive this
to FAT
Build Process – cont.
Internal
view of
half--suit
half
interfaced
with lyo on
this same
design prepreFAT
Lyo Door Interface
Door Design & clearance
ties into Half-suit design &
position.
Davit style
Swing bolts
Recessed wall flange
FAT photo – internal view of inlet & integrated filler
Fully Integrated @ FAT
Equipment is
mechanically and
electrically integrated
@ vendor cleanroom
site for full FAT checkouts and protocol
execution
Photo shows the Lyo
mounted to the flange
on the outside of the
Isolator.
FAT Testing
Tests range
from as
simple as
surface finish
&
dimensional
checks
To more
involved DOE
type studies:
UAF & airflow
smoke testing
Shipping & Installation Preparations
Equipment is
broken down to
the key
dimensions for
door and room
clearances &
reassembled
on-site
In this particular
case, the
design required
all HVAC and
components on
top of the shell
to be removed
Outer view in facility
All upper
HVAC, valving,
& components
are covered by
stainless steel
flashing.
The shell
conforms to
the angles in
the drawing
and mock-up
needed to
accommodate
the room
constraints and
process.
Conclusions:
Design is key, but it takes a good team with specified tasks and
understanding of what alleviates big timing & costs consequences for
both the vendor & client
No matter how off the shelf the Pharma industry tries to push to for process
equipment, there continues to be a growing need for custom design due to a
multitude of circumstances.
Overall....no matter how unique an application, if the correct
steps are put in place to validate feasibility studies from both the
clients needs and vendors capabilities, in the end you can and
will always find an optimal solution.
Thank You
Q&A