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 � Dealing with existing equipment for design interface 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 of 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
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 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, oven, 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 outside 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- outs and protocol outs 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 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 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 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
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