Flexible Containment Concepts in Real Application

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Flexible Containment Concepts in Real Application

• Jon Gast
• Steven Meszaros
• PSG 2009

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PSC Guideline Presentation Overview

• RBEC History
• Motivation
• Scope
• Strategy
• Expectations
• Gap Analysis RBEC Checklists
• Fixed Containment
• Flexible Containment Solutions

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PSC Guideline History

• OC Technical Guidelines - 1994
• RBEC Guideline -1998, revised 2001
• RBEC Interpretation Guideline - 2002
• PSC Task Force 2003
• PSC Guideline 2004 EHS Policy 404
• IH Policy 401
• Containment Technology Matrix (CTM) 2009

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PSC Guideline Motivation

• Regulatory Requirements
• API Product Cross Contamination
• Worker Health Safety
• Environmental Air, Water Waste - PNAEELs
• Third Party Contractual Obligations Liability
• cGMP Harmonization - CS 14-8-4
• OHC, OEGs and RBEC levels
• Aligned with RD TOPS Decision Gates

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Historical PSC Risk Control Issues

• Pre-RBEC Facility Designs Equipment
• Historical levels gt 1,000 X OEG
• Cross Contamination Potential
• Pharmaceuticals In the Environment

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Real Risks
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PSC Guideline Scope

• RD API Manufacturing Handling
• Pharmaceutical Manufacturing
• BioPharmaceutical Manufacturing
• New Products Facilities and Areas
• Renovated Facilities and Areas
• Third Party Manufacturing
• Requires project-specific RBEC Criteria
  interpretation - -The key is to design is to meet
  our OEG !

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Rollout Strategy

• Endorsement from TOPS
• and RD senior management
• Stakeholder meetings planned for
• TOPS, RDCPD/PDC
• GES, GSS, QA
• Major Solid Dosage Sites
• Key PSC manufacturing Sites

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PSC Guideline New Expectations

• Responsibilities Defined
• Timelines for Conformance Specified
• cGMP Cross Contamination Harmonization of
  Engineering EHS approaches
• GAP Analysis
• Short Term, Long Term Actions
• Conformance Action Plans Site Master Plans

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RBEC Risk Based Exposure Control

• 4-Tier Banding System
• Aligned to OEG
• Conforms to Pharmaceutical Industry
• Hierarchy of Controls
• Engineering Project Guidance
• RBEC Criteria Tables
• Containment Technology Matrix

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PSC RBEC Criteria Table Gap Checklist

• Facility Design for Containment
• Room Work Surfaces
• HVAC Systems
• Local Exhaust Ventilation
• Process Equipment
• Unit Operations milling, blending, sieving, etc.

• Product Transfers
• Maintenance Cleaning
• Medical Surveillance
• Work Methods SOPs
• PPE Respirators
• Waste Containment Disposal
• cGMP Regulatory conformance

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PSC GAP Assessment

• Facility Team EHS, Engineering, management, and
  Quality Assurance.
• RBEC Gap Checklist - For each API by area,
  process or unit operations.

RBEC 3 Gap Checklist
 
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API Dispensing Containment
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New Technologies Bin Blending
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Surrogate Testing Protocol Containment Technology
Matrix

• Real conditions
• Assume sub-optimal technique
• Worst case operator shift

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PDC CONTAINMENT PROJECT AN OVERVIEW
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Facility Airlocks Added
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Facility Expansion of Process Areas
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Flexible Containment Systems Summary
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Flexible Containment Concept Designs
Note Glove-ports in not shown in all concept
sketches. Blender and Mi-Pro SMI system not
shown
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Transfer Systems

• All the isolator systems provided with a Bag
  in/out canister to allow contained transfer in
  and out of materials. The canister is 11.73
  internal diameter.
• This canister also serves a duel purpose of
  allowing connection of the In-Process Isolator to
  them. Canisters are mounted at standard height to
  allow easy connection.
• The only isolators that the In-Process isolator
  can not connect to directly are the Extruder and
  Spheronizer systems (due to height issues.). A
  connection can be made using a length continuous
  liner if it is required.

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In-Process Isolator
The In-Process Isolator is a general purpose
piece of equipment designed to allow any number
of tasks to be carried out. It can be used
independently or connected to other flexible
isolator systems as shown.
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Typical Process Flow
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Typical Process Flow
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Typical Process Flow
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Extruder Spheronizer Design Progress
Flange Mock Up
Flanges Installed
Finalized 3D Design Drawing
Enclosure Installed December2008
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Glatt GPCG1 Design Progress
Ergonomic Flange Mock Up
Finalized 3D Design Drawing
Enclosure Installed December 2008
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Korsch Design Progress
Finalized 3D Design Drawing
Enclosure Installed December 2008
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Procept SMI Press
SMI Press Flange Installed
Enclosure Installed December 2008
Procept Final Design

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Strea Design Progress
Finalized 3D Design Drawing for Flange
Enclosure Installed December 2008
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Roller Compactor Design Progress
Finalized Design Concept Final Assembly Shipped
to Newbridge December 2008
Gerteis Mini-Pactor
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Bohle BTS-100 Cone Mill
Finalized 3D Design Drawing
Enclosure Installed December 2008
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Collette UltimaGral 10 25 Liter
Finalized 3D Design Drawing
Enclosure Installed December 2008
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Installation Training
Training Carried Out January 2009