Filling line & Lyo Interface (one Isolated system) Case Study - - PowerPoint PPT Presentation

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 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)? 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
• f these systems & vial capacity)

Existing Transfer Isolator

• This is a turbulent

flow system.

• Mobile design

(moves from room to room) room)

• Decontaminated with

a remote vHP generator

• Feasibility of Isolation HVAC around layout
• What are the necessary filling line speeds & lyo capacity
• How does one transfer vials from filler to lyo

From concept to details

• 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 pre- sterilize empty vials before transfer from 3-glove to Filler Process doesn’t stop with just the filling, there is a just the filling, there is a chain of Isolation required in many to most cases. Ie) formulation, autoclave,

• ven, sterility testing.

Outfeed Sterility Testing

• Samples are taken from

the Filler to a dedicated Sterility Testing Isolator as well.

• Every piece of Isolated
• 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
• 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

• utside the Isolator.
• Easier to have

media outside as 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 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 mock- up to 3D layout.

• 3D prints not only

give good visual 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 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 ‘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 The fabrication of the shell: view of the interface for the Lyo

Once system Once system is vendor is vendor manufacturin manufacturin g, it is g, it is extremely extremely difficult to difficult to change the change the design. design. At this point it At this point it At this point it At this point it is in the is in the hands of hands of vendor vendor Project Project Management Management to drive this to drive this to FAT to FAT

Build Process – cont.

Internal Internal view of view of half half-suit suit interfaced interfaced with lyo on with lyo on this same this same design pre design pre- FAT FAT FAT FAT

Lyo Door Interface

Door Design & clearance ties into Half-suit design & position. Davit style Swing bolts 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 check-

• uts and protocol
• uts and protocol

execution

• Photo shows the Lyo

mounted to the flange

• n the outside of the

Isolator.

FAT Testing

• Tests range

from as simple as surface finish & dimensional 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 reassembled

• n-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
• 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